Medical Biochemistry - Final Exam

Front 1

What is a nucelosome?

Back 1

Histone core + linker DNA

Front 2

Which bacterial DNA polymerase has 5´to 3´exonuclease activity? And why is it important?

Back 2

Polymerase I

Primer removal and DNA repair

Front 3

Which DNA polymerase has 3´to 5´exonuclease activity? And why is it important?

Back 3

Polymerase I, II and III

Proofreading and error correction of the newly synthesized DNA strand.

Front 4

What does it mean that replication is semiconservative?

Back 4

Each DNA strand serve as a template for the synthesis of a new DNA strand producing 2 new DNA molecules, each with 1 old and 1 new DNA strand.

Front 5

In which direction does DNA synthesis happen?

Back 5

DNA synthesis is allways in a 5 ́to 3 ́direction.

Front 6

What is the role of Dam methylase?

Back 6

Methylates the newly synthesized DNA strand.

The two strands can no longer be distinguished.

Front 7

Methyl directed mismatch repair (the enzymes and their function)

Back 7

MutS, MutL, MutH: winds up the DNA molecule

MutH: cleaves the unmethylated strand at methylated site

DNA helicase: unwinds the DNA strand

Exonuclease I: removes the newly synthesized fragment from the MutH cleavage site to just beyond the mismatch

DNA polymerase III: makes the new strand

Front 8

Base-excision repair pathway (the enzymes and their function)

Back 8

DNA glycosylase: recognize common DNA lesions and remove the affected base (AP site is formed)

AP endonuclease: cut the DNA strand containing the AP site. A segment of DNA including the AP site is removed.

DNA polymerase I: replaces the removed DNA

DNA ligase: seals the remaining nick

Front 9

Nucleotide excision repair (the enzymes and their function)

Back 9

DNA lesion is detected.

Exinuclease: cleaves the DNA on each side of the damage.

DNA helicase: removes the DNA segment.

DNA polymerase (I in Ecoli, ε in human): fills the gap

DNA ligase: seals the nick

Front 10

What are the different types of direct repair of DNA molecules?

Back 10

1. Repair of pyrimidine dimers with photolyase

2. Direct repair of O^6-Methylguanine by O^6-Methylguanine-DNA methyltransferase

- Transfers the methyl group onto its own Cys-residue

3. Direct repair of alkylated bases by AlkB

- α-ketoglutarate donates a hydroxyl group to the alkylated base and in next step the methyl group is removed in the form of an aldehyde group.

Front 11

What are the different types of short RNAs?

Back 11

miRNA, siRNA, saRNA, snRNA, snoRNA, rasiRNA piRNA, qiRNA, tmRNA, gRNA

Front 12

What are the different types of RNA molecules and their function?

Back 12

mRNA: Encode the amino acid sequence of one or more polypeptides specified by a gene or a set of genes.

tRNA: Read the information encoded in the mRNA and transfer an amino acid to the growing polypeptide chain in protein synthesis.

rRNA: Are constituents of ribosome.

Front 13

Examples of ribozymes

Back 13

Ribozymes = ribonucleic acid enzymes. They increase the speed of reaction.

Group I introns

Rnase P

rRNA

Spliceosomes

Hammerhead ribozyme

Front 14

What is the role of Sigma factor?

Back 14

Sigma factor is a bacterial transcription initiation factor that enables specific binding of RNA polymerase to gene promoters. It controls promoter recognition and specificity.

Front 15

What is the function of the Rho factor?

Back 15

Prokaryotic protein involved in the termination of transcription.

Front 16

What inhibits transcription in bacteria? (name and function)

Back 16

Tetracycline: blocks binding of aminoacyl-tRNA to A-site of ribosome.

Streptomycin: prevents the transition from initiation complex to chain-elongating ribosome and also causes miscoding

Chloramphe-nicol: blocks the peptidyl transferase reaction on ribosomes

Erythromycin: blocks the translocation reaction on ribosomes

Rifampicin: blocks initiation of RNA chains by binding to RNA polymerase (prevents RNA synthesis)

Front 17

What inhibits transcription in both bacteria and eucaryotes? (name and function)

Back 17

Puromycin: causes the premature release of nascent polypeptide chains by its addition to growing chain end.

Actinomycin D: binds to DNA and blocks the movement ofRNA polymerase (prevents RNA synthesis)

Front 18

What inhibits transcription only in eukaryotes? (name and function)

Back 18

Cycloheximide: blocks the translocation reaction on ribosomes

Anisomycin: blocks the peptidyl transferase reaction on ribosomes

α-Amanitin: blocks mRNA synthesis by binding to RNA polymerase.

Front 19

What is the function of 5´cap?

Back 19

- Protect mRNA and prevent degradation by endonucleases.

- Promotion of ribosome binding and translation

- Regulates nuclear export

Front 20

What is the function of poly (A)?

Back 20

- Protection

- Transport

- Translational enhancement

Front 21

What is the difference between virus and retrovirus?

Back 21

Virus contain both DNA and RNA, retrovirus contain only RNA.

Viruses have transcription process, whereas retroviruses have reverse transcription process. It needs to convert their RNA into DNA before it can insert it into the host genome.

Front 22

What is transposon/retrotransposon?

Back 22

DNA sequence that can change its position within the genome, sometimes causing mutations and altering the genome size.

Front 23

What is the function of molecular chaperones? And what are the members of the chaperone family?

Back 23

Molecular chaperones: proteins assisting folding of nascent polypeptides, by preventing wrong folding.Molecular chaperones catalyze the formation of correctly folded, functionally active, native proteins, but they are not part of the product.

Chaperone family:

- Nucleoplasmins

- Chaperonins

- Heat Shock proteins 70 (HSP 70)

- Heat Shock proteins 90 (HSP 90)

Front 24

What is heat shock proteins?

Back 24

Expression of many chaperones is induced by stress, such as by heat,because during heat-stress the probability of wrong folding is higher, therefore cells need more protection.These chaperons are called heat shock proteins (HSP’s).

Front 25

Examples of diseases due to misfolding of proteins

Back 25

Cystic fibrosis mutant

Parkinson’s disease

Alzheimer’s disease

Huntington’s disease

Front 26

Hoe does protein degradation happens in eukaryotes and bacteria respectively?

Back 26

Eukaryotes: Ubiquitination (signal of death for proteins) and proteasome (enzyme where proteins are degraded)

Bacteria: Lon (an ATP dependent protease) and other proteases

Proteins are degraded into short peptides, and not amino acid. This is important for immune surveillance.

Front 27

What are the 7 processes that can affect the steady-state concentration of a protein?

Back 27

1. Transcription

2. Posttranscriptional processing

3. mRNA degradation

4. Translation

5. Posttranslational processing

6. Protein degradation

7. Protein trageting and transoprt

Front 28

Gene regulatory mechanisms

Back 28

1. Transcriptinal mechanims (promoter and RNA polymerases)

2. RNA porcessing (5´capping, 3´poly-adenylation, splicing and alternative splicing)

3. Translational mechanisms (miRNA inhibit translation and degrade mRNA, silencer RNAs degrading mRNA)

3. Epigenetic mechanisms (DNA methylation, histone modification, chromatin remodeling)

Front 29

What are enhancers elements?

Back 29

DNA sequence with no promoter activity of their own, but they that increase the activities of many promoters in eucaryotes. Enhancers function by serving as binding sites for specific regulatory proteins.

It increase the rate of transcription.

Front 30

What are the 3 transmit messages between cells?

Back 30

1. Neurotransmitters - nervous system

2. Hormones - Endocrine system

3. Cytokines - immune system

Front 31

Peptide hormones

Back 31

Insulin, glucagon, somatostatin, hypothalamic (releasing) hormones, pituitary hormones

Synthesis: proteolytic cleavage of the precursor proteins

Mode of action: bind to receptors in the plasma membrane

Front 32

Catecholamine hormones

Back 32

Epinephrine and norepinephrine

Synthesis: brain, adrenal glands

Mode of action: act through plasmamembrane receptors

Effects: increased heart rate and blood pressure (increased delivery of O2 to tissues). Increased glucose and ATP production, fatty acid mobilization. Increased glucagon secretion and decreased insulin secretion.

Front 33

Eicosanoids (fatty acid derivatives)

Back 33

Derived from polyunsaturated fats and produced only when needed. They are paracrine hormones.

Prostaglandins, thromboxanes and leukotrienes

Mode of action: act through plasma membrane receptors.

They are involved in inflammation, fever and painassociated with injury or disease, in the formationof blood clots and the regulation of bloodpressure.

Front 34

What is the role of phospholipase A2?

Back 34

- Phospholiase A convert phospholipids to arachidonate.

- Arachidonate --> leukotrienes by lipoxygenase.

- Arachidonate --> prostaglandins and thromboxanes by cyclooxygenase.

Front 35

Steroids

Back 35

Steroid hormones are endocrine hormones.

Derived form cholesterol: Cortisol, progesterone, testosteron.

Front 36

What is the mode of action of steroid hormones?

Back 36

Front 37

Vitamin D

Back 37

Mode of action: acts through nuclear receptors (intestinal Ca2+-binding protein) --> uptake of dietary Ca2+

Effects: works in Ca2+ homeostasis,regulating balance between Ca2+ deposition and Ca2+ mobilization from bone.

Front 38

Retionic acid hormones

Back 38

Regulation of gene expression

Biosynthesis: In liver from vitamine-A

Mode of action: Nuclear receptors

Effects: regulate the growth, survival,and differentiation of cells.

Front 39

Thyroid hormones

Back 39

Thyroglobulin-Tyr ---> Thyroglobulin-Tyr-I (iodinated Tyr residues) ---> Thyroxine (T4) and triiodothyronine (T3)

Mode of action: through nuclear receptors

Effects: stimulate energymetabolism in the liver and muscle

Front 40

Describe the desensitization of the beta-adrenergic receptor by epinephrine.

Back 40

Front 41

The genes which expression are supressed by insulin.

Back 41

- PEP carboxykinase (gluconeogenesis)

- Glucose-6-phosphatase (release glucose to blood)

Front 42

The genes which expression are increased by insulin.

Back 42

Glycolysis: Hexokinase 2, Hexokinase 4, phosphofructokinase-1, pyruvate kinase

Regulation of glycolysis/gluconeogenesis: PFK-2/FBPase-2

Pentose phosphate pathway: glucose-6-phosphate dehydrogenase, 6-phosphogluconate dehydrogenase

Fatty acid synthesis: pyruvate dehydrogenase, acetyl-CoA carboxylase, malice enzyme, ATP-citrate lyase, fatty acid synthase complex

Front 43

What enzymes are regulated by PKA?

Back 43

Increase:

- Phosphorylase b kinase (glycogen breakdown)

- Fructose-2,6-bisphospatase-2 (gluconeogenesis)

- Hormone-sensitive lipase (triacylglycerol mobilization and fatty acid oxidation)

Decrease:

- Glycogen synthase (glycogen synthesis)

- Pyruvate kinase (glycolysis)

- Pyruvate dehydrogenase complex (pyruvate to acetyl-CoA)

- Phosphofructokinase-2 (glycolysis)

Front 44

What are the metabolic functions of PKB?

Back 44

- Translation initiation

- Translation elongation

- Increase glucose uptake (by stimulating GLUT4 transporter)

- Stimulate glycolysis (by increase prod. of PFK2)

- Increase glycogen synthesis (by inhibiting GSK-3)

Front 45

What is AMPK stimulated by and what does it stumulates?

Back 45

It is stimulated by stress, exercise, fasting ( increased [AMP])

It stimulates glucose uptake and transport, glycolysis, fatty acid uptake, beta-oxidation

Front 46

What does AMPK inhibit?

Back 46

- HMG-CoA reductase (cholesterol synthesis)

- Fatty acid synthesis (ACC - acetyl-CoA carboxylase)

- Insulin secretion

- Transcription

Front 47

What happens if there is hypoxia (low pO2)?

Back 47

1. Increased transcription of HIF-1α. HIF-1 regulates gene expression to reduce ROS formation

2. HIF-1α is phosphorylated

3. HIF-1α increases transcription of other enzymes and proteins (glucose transporter, glycolytic enzymes, lactate dehycrognease, protease)

4. --> ATP production by glycolysis increases and complex IV properties are adapted to low pO2.

Front 48

How is the cholesterol synthesis regulated?

Back 48

Intracellular cholesterol concentration: High intracellular concentrations has a negative feedback and stimulate proteolysis of HMG-CoA reductase. It activate ACAT, which increase esterification of cholesterol for storage. A high cellular cholesterol level also diminishes transcription of the gene that encodes the LDL receptor, reducing production of the receptor and thus the uptake of cholesterol from the blood.

Hormonal regulation: stimulated by insulin and inhibited by glucagon. Covalent modification of HMG-CoA reductase. Glucagon stimulates phosphorylation which inactivates the enzyme, while insulin promotes dephosphorylation, activating the enzyme.

Transcriptional regulation:

SREBP activates HMG-COA reductase as a transcription factor.

SCAP (cleavage-activating protein) prevents release of SREBP.

Front 49

Which enzymes uses TPP (thiamin diphosphate) as a cofactor?

Back 49

Catalyze oxidative decarboxylation:

- Pyruvate dehydrognease

- a-ketoglutarate dehydrogenase complex

- Branched-chain keto-acid dehydrogenase

- Pyruvate decarboxylase (in bacteria)

Also a coenzyme for transketolase in pentose phosphate pathway.

Front 50

Which enzyme are vitamin B12 dependent enzymes?

Back 50

- Methymalonyl CoA mutase

- Methionine synthase

- Leucine aminomutase

Front 51

Which enzymes uses biotin as a coenzyme?

Back 51

- Acetyl-CoA carboxylase

- Pyruvate carboxylase

- Propionyl-CoA carboxylase

- Methylcrotonyl-CoA carboxylase

Front 52

What function has riboflavin (B2)?

Back 52

Water-soluble vitamin

Coenzyme in oxidation and reduction reactions (FAD)

Prosthetic group of flavoproteins

Front 53

What function has nicotinic acid/nicotinamide (niacin)?

Back 53

Coenzyme in oxidation and reduction reactions, functional part of NAD and NADP.

Front 54

Lipid-soluble vitamins

Back 54

Hydrophobic compounds. Can be absorbed efficiently only whenthere is normal fatabsorption Are transported in theblood in lipoproteins or attached to specificbinding proteins.

D - Calciferol

E - Tocopherols, tocotrienols

K - Phylloquinone: menaquinones

A - Retinol, b-Carotene

Front 55

Water-soluble vitamins

Back 55

Hydrophilic compounds. Function mainly as enzyme co-factors.

B1 - Thyamin (TPP)

B2 - Riboflavin (FAD)

B3 - Niacin (NAD/NADP)

B5 - Panthotenic Acid (part of CoA and ACP)

B6 - Pyridoxin (PLP)

B7 - Biotin

B9 - Folic acid

B12 - Cobalamin

C - Ascorbic Acid

Front 56

What are the different types of glucose transporters and their function?

Back 56

GLUT-1

- RBC, brain

- Transport across blood-brain barrier

GLUT-2

- Liver, kidney, pancreas

- Regulation on insulin release

GLUT-3

- Brain, placenta, others

- Uptake into neurons

GLUT-4

- Muscle, adipose tissue

- Insulin-mediated transport

GLUT-5

- Kidney and gut

- Absorption of fructose

Front 57

What is the difference between hexokinase II and IV?

Back 57

Hexokinase II is in muscle cells, have high affinity for glucose and is inhibited allosterically by its product glucose-6-phosphate.

Hexokinase IV (glucokinase) is in liver cells, have low affinity for glucose and is inhibited by a regulatory protein (not G6P). It is activated by glucose or fructose-6-phosphate.

Front 58

How is phosphofructokinase-1 (PFK1) regulated?

Back 58

Allosteric regulation.

Activated by ADP, AMP and fructose-2,6-bisphosphate (F2,6BP).

Inhibited by ATP and citrate.

(Citrate serves as an intracellular signal that the cell is meeting its current needs for energy-yielding metabolism by the oxidation of fats and protein)

Front 59

What is the role of fructose-2,6-bisphosphate in regulation of glycolysis and gluconeogenesis?

Back 59

F2,6P is formed by phosphofructokinase 2 (PFK2). It is an allosteric regulator of PFK-1 and FBPase-1. They are regulated reciprocal. PFK2 is activated by insulin and inhibited by glucagon (↑ [cAMP]).

Increased F26BP stimulates glycolysis and inhibits gluconeogenesis. Decreased F26BP inhibits glycolysis and stimulates gluconeogenesis.

Front 60

How is pyruvate kinase regulated?

Back 60

In all glycolytic tissues: (M pyruvate kinase)

Activated by fructose 1,6-bisphosphate

Inhibited by ATP, alanine, acetyl CoA, long chain fatty acids.

Only in the liver: (L pyruvate kinase)

Low blood glucose --> glucagon release --> cAMP-dependent protein kinases phosphorylates the L (liver) isozyme of pyruvate kinase via PKA. This inactivates the enzyme.

Front 61

What are the 3 possible catabolic fates of the pyruvate formed in glycolysis?

Back 61

Gluocose --> 2 pyruvate

1. 2 lactate

- Under anaerobic conditions

- Lactate dehydrogenase

2. 2 acetyl- CoA

- Enter citric acid cycle)

- Under aerobic conditions

- Pyruvate dehydrogenase complex

3. 2 ethanol + 2 CO2

- Only in bacteria!

- Pyruvate decarboxylase + alcohol dehydrogenase

Front 62

One reaction which acetyl-CoA inhibit and one reaction which acetyl-CoA stimulate.

Back 62

Inhibit: pyruvate kinase, pyruvate dehydrogenase complex

Stimulate: pyruvate carboxylase

Front 63

How is pyruvate dehydrogenase complex (PDC) regulated?

Back 63

Inhibited by ATP, acetyl-CoA, NADH and fatty acids.

Activated by AMP, CoA, NAD+, Ca2+.

Pyruvate dehydrogenase kinase (PDK) phosphorylates PDC --> INACTIVE

Pyruvate dehydrogenase phosphatase (PDP), dephosphorylates PDC ---> ACTIVE

PDK is stimulated by NADH and acetyl-CoA, and inhibited by CoA-SH, NAD+, ADP, pyruvate.

PDP is stimulated by Ca2+, Mg2+, insulin

Front 64

How is citrate synthase regulated?

Back 64

Inhibited by NADH, succinyl- CoA, citrate, ATP

Activated by ADP.

Front 65

How is the gluconeogenesis regulated hormonally?

Back 65

Insulin: inhibit

Glucagon: stimulate

Epinephrine, norepinephrine: stimulate

Glucocorticoids: stimulate

Front 66

How is the glycogen synthase regulated?

Back 66

Glycogen synthase has two forms, a (active) and b (inactive).

GSK3 = glycogen synthase kinase 3. Casein kinase (CKII) phosphorylates GSK3 for activation. GSK3 phosphorylates the glycogen synthase , form glycogen synthase b and inhibits glycogen synthesis. It is inhibited by insulin. Insulin will trigger activation of glycogen synthase a by blocking the activity of GSK3, and activating PP1 in muscles.

PP1 dephosphorylates glycogen synthase b forming glycogen synthase a. This promotes glycogen synthesis. PP1 is activated by insulin, glc-6-P and glc, and inhibited by glucagon and epinephrine.

Front 67

What are the different enzymes that regulates different processes in lipid metabolism?

(biosynthesis of FA, β-oxidation, cholesterol biosynthesis, ketonebodies, signal transduction)

Back 67

- Regulation of biosynthesis of FA: ACC

- Regulation of β-oxidation: CAT

- Regulation of cholesterol biosynthesis: HMG-CoA-reductase, transcriptional regulation

- Regulation of ketonebodies: succinyl-CoA

- Regulation of lipid metabolism by signal transduction (AMPK, PPAR)

Front 68

What are the hormones that regulates lipid metabolism?

Back 68

Insulin, glucagon, glucocorticoids, epinephrine

Front 69

In which intracellular compartments does the different lipid metabolism processes happen?

Back 69

Cytosol: Fatty acid synthesis (up to C16), cholesterol synthesis

ER: phospholipid synthesis, fatty acid elongation, fatty acid desaturation

Mitochondria: fatty acid oxidation, acetyl-CoA production, ketone body synthesis, fatty acid elongation

Front 70

How is Acetyl-CoA carboxylase (ACC) regulated?

Back 70

Inactivated by when phosphorylated by AMP-activated protein kinase. Glucagon, adrenaline, AMP, palmitoyl-CoA --> phosphorylation of ACC.

Protein phosphatase 2A dephosphorylates ACC and activating it. Glucagon inhibits protein phosphatase A2. It is activated by insulin and citrate.

Front 71

How is the formation of ketone bodies regulated?

Back 71

Regulation of ketone body synthesis happens via mitochondrial HMG-CoA synthase.

Stimulated by acetyl CoA.

Inhibited covalently by succinyl-CoA

Front 72

Write with structures the reaction that is defective in phenylketonuria (PKU).

Back 72

Defect phenylalanine hydroxylase.

Front 73

Write with structures the reaction that is defective in Maple syrup urine disease.

Back 73

Defect branched-chain alfa-keto acid dehydrogenase complex.

Front 74

Write with structures the reaction that is defective in Tyrosinemia I.

Back 74

Defect fumarylacetoacetase.

Front 75

Write with structures the reaction that is defective in Tyrosinemia II.

Back 75

Defect tyrosine aminotransferase.

Front 76

Write with structures the reaction that is defective in Tyrosinemia III.

Back 76

Defect p-hydroxyphenylpyruvtae dioxygenase.

Front 77

Write with structures the reaction that is defective in Citrullinemia type I.

Back 77

Argininosuccintae synthetase deficiency.

Front 78

Write with structures the reaction that is defective in argininocsuccinate aciduria.

Back 78

Argininosuccinase deficiency

Front 79

Write with structures the reaction that is defective in homocystinuria I.

Back 79

Cystathionine ß synthase deficiency.

Front 80

Write with structures the reaction that is defective in argininemia.

Back 80

Argininase deficiency.

Front 81

Write with structures the reaction that is defective in alkaptonuria.

Back 81

Homogentisate-1,2-dioxygenase deficiency.

Front 82

Write with structures the reaction that is defective in methylmalonic aciduria.

Back 82

Methylmalonyl-CoA mutase deficiency.

Front 83

What is the function of intestinal lipase?

Back 83

Degradation of triglycerols to diacylglyderides and monoacylgylcerols in the intestines.

Front 84

What is the function of apoprotein?

Back 84

- Structural role in lipoproteins

- Regulation of enzymes

- Targeting the lipoproteins: Lipid-binding protein in blood, transport phospholipids, cholesterol and cholesterol esters between organs.

Front 85

What is the function of lipoprotein lipase?

Back 85

Converts triacylglycerols in lipoproteins to fatty acids and glycerol.

Front 86

What is the function of hormone-sensitive lipase?

Back 86

Mobilization of stored triacylglycerols in adipocytes.

Stimulated by glucagon/adrenaline

-- > PKA activates hormone-sensitive lipase through phosporylation --> triacylglycerols are hydrolyzed --> free fatty acids are released into the blood.

Front 87

What is the function of serum albumin in lipid metabolism?

Back 87

Binds fatty acids and transports them through the blood.

Front 88

What is the CORI cycle

Back 88

When lactate is formed by active skeletal muscles (or RBC), it can be recycled. It is carried to the liver by the blood, and in the liver it is first converted to pyruvate, and then to glucose by gluconeogenesis. The glucose then returns to muscle through the blood and is again used for energy.

Front 89

Galactosemia

Back 89

Defect in either galactokinase, galactose-1-phosphate uridylyltransferase or UDP-glucose-4-epimerase.

Front 90

What are the inhibitors of complex I, III and IV in the respiratory chain and the ATP synthase?

Back 90

Complex I: rotenone, amytal, piercidin A

Complex III: antimycin A, myoxothiazol

Complex IV: CN- (cyanide) and CO

ATP synthase: oligomycin, venturicidin

Front 91

What are the most common uncoupling agents in the ATP synthesis?

Back 91

DNP (2,4-dinitrophenol

FCCP

Causing the oxidation to continue even if ATP synthesis is blocked.

Front 92

What is the function and location of the malate-aspartate shuttle?

Back 92

System that transport the NADH generated by glycolysis in the cytosol into the mitochondrial matrix. The mitochondrial membrane is not permeable to NADH.

Functions in liver, kidney, and heart mitochondria.

Front 93

Glycerol-3-phosphate shuttle (function and location)

Back 93

NADH shuttle used in skeletal muscle and brain.

NADH in cytosol is converted to FADH2 in the mitochondrial matrix

Electrons are transported to complex II.

Front 94

What are the sources of reactive oxygen species (ROS)?

Back 94

- CoQ of the respiratory chain

- Production of ROS in the peroxisome

- Cytochrome P450 monoxygenases

Front 95

What is the function of antioxidants and name some examples?

Back 95

Enzymes and other molecules that help protect the cell from harmfull effects of ROS.

Superoxide dismutase

Catalase

Glutathione: oxidized to donate reducing equivalents to regenerate oxidized cellular molecules

Front 96

Where does the gluconeogenesis takes place and what is its function?

Back 96

Takes place in the liver.

Function is to maintain the blood glucose levels during fasting.

Front 97

How is the gluconeogenesis regulated?

Back 97

Activators: Acetyl Coa, glucagon, epinephrine, norepinephrine, glucocorticoids

Activators of glycolysis (inhibitors of gluconeogensis): ADP, AMP, citrate, fructose-2,6-bisphosphate, insulin.

Front 98

What is the function of the pentose phosphate pathway and in which cells is it present?

Back 98

Location: rapidly dividing cells, such as those of the bone marrow, skin and intestinal mucosa.

Function: uses ribose-5-phosphate to produce NADH, RNA, DNA, ATP, FADH2 and CoA.

In other tissues, the essential product of the pen-tose phosphate pathway is not the pentoses but theelectron donor NADPH, needed for reductive biosynthesis or to counter the damaging effects of oxygen radicals.

Front 99

Which pathways requires NADPH created by the pentose phosphate pathway?

Back 99

Synthesis:

- fatty acid biosynthesis

- cholesterol biosynthesis

- neurotransmitter biosynthesis

- nucleotide biosynthesis

Detoxification:

- reduction of oxidized glutathione

- cytochrome P450 monooxygenases

Front 100

What does glucose-6-phosphate dehydrogenase deficiency lead to?

Back 100

Glucose-6-phosphate dehydrogenase deficency lead to NADPH deficiency.

NADPH maintains the supply of reduced glutathione in the cells that is used to remove free radicals that cause oxidative damage.

Gluthahtione peroxidase: 2GSH + H2O2 ---> GSSG + 2H2O.

The G6PD/NADPH pathway is the only source of reduced glutathione in red blood cells (erythrocytes). If there is not enough reduced glutathione in the cells the free radicals produce Heinz bodies in the RBC, which is denatured hemoglobin caused by oxidative stress.

Front 101

What is the Wernicke-korsakoff syndrome?

Back 101

Mutation in transketolase gene, affinity to TPP is decreased --> thiamine deficiency (vitamin B1) --> entire pentose phosphate pathway slows down

Symptoms: severe memory loss, mental confusion and partial paralysis.

Front 102

Where is glycogen stored and what is the function?

Back 102

Glycogen is stored in liver and skeletal muscle.

Liver glycogen is used to maintain blood glucose levels.

Muscle glycogen is used to generate ATP for muscle contraction when is needed.

Front 103

Which enzymes are needed for glycogen synthesis?

Back 103

- Hexokinase/glucokinase

- Phosphoglucomutase

- UDP-glucose pyrophosphorylase

- Glycogen synthase

- Glycogen branching enzyme

Front 104

What is the function of glucogenin?

Back 104

Primer for glycogen synthesis.

Glycogenin catalyzes the addition of glucose to itself (autocatalysis) by firstbinding glucose from UDP-glucose to the hydroxyl group of Tyr-194. Seven moreglucoses can be added, each derived from UDP-glucose, by glycogenin'sglucosyltransferase activity. Once sufficient residues have been added, glycogensynthase takes over extending the chain. Glycogenin remains covalently attached tothe reducing end of the glycogen molecule.

Front 105

Which enzymes are needed for glycogen degradation (glycogenolysis)?

Back 105

- Glycogen phosporylase

- Debranching enzyme

- Phosphoglucomutase

- Glucose-6-phosphatase

Front 106

How is glycogen phosphorylase regulated?

Back 106

Glycogen phosphorylase has 2 forms, glycogen phosphorylase a (more active) and glycogen phosphorylase b (less active)

Glycogen phosphorylase a is activated by phosphorylase b kinase by phosphorylation. Epinephrine, Ca2+, AMP will activate the kinase in muscle, while glucagon will activate it in liver. Will activate via cAMP --> PKA. PKA phosphorylates and activates phosphorylase kinase.

Glycogen phosphorylase is dephosphorylated by PP1 which makes it less active.

Glycogen phosphorylase in liver has glucose sensor. Glucose will bind to an allosteric site of phosphorylase a (PP1), and this causes a change in conformation which exposes it's phosphorylated groups. The PP1 will convert it to phosphorylase b. Reducing the activity, and slowing glycogen breakdown. Also stimulated by insulin indirectly.

Front 107

How many citrate molecules are needed frommitochondria to cytosol to synthesize palmitate?

Back 107

8 (Synthesis of palmitate need 8 acetyl-CoA = 8 citrate)

Acetyl CoA from pyruvate cannot be transported through the mitochondrial membrane to the cytosol, so it forms citrate together with oxaloactetate, which is transported out through a citrate transporter.

In the cytosol, citrate is reconverted to acetyl-CoA and oxaloacetate, and acetyl CoA process to fatty acid synthesis in the cytosol. Oxaloacetate is reduced to malte and is transported back into the mitochondria.

Front 108

What is special with the desaturation of fatty acids in animals?

Back 108

Animals can only put double bonds before the 10th carbon.

Therefore it is essential for animals to have fatty acids with double bonds >10 in their diet, like inolenate and alfa-linolenate which are essential fatty acids for mammals

These can be made into arachidonate, which can turn into prostaglandins, thromboxanes and leukotrienes.

Front 109

What inhibit the production of prostaglandins, thromboxanes, leukotrienes?

Back 109

Steroids inhibit the synthesis of arachidonate from phospholipids ---> no prostaglandins, thromboxanes or leukotrienes.

Non-steroids (aspirin, ibuprofen) inhibit COX (cyclooxygenase) ---> prostaglandins or thromboxanes.

Front 110

What is the common precursor for both ketone bodies and cholesterol, and what is the enzymes for the different synthesis reactions?

Back 110

HMG-CoA (beta-hydroxy-beta-methylglutaryl CoA)

Synthesized from acetyl-CoA and acetoacetyl-COA by HMG-CoA synthase-

Mitochondria:

HMG-CoA lyase --> acetoacetate (ketone body) + acetyl CoA

Acetoacetate --> acetone (acetoacetate decarboxylase) and D-beta-hydroxybutyrate (hydroxybutyrate dehydrogenase)

Cytosol:

HMG-CoA reductase --> mevalonate (cholesterol synthesis)

Front 111

What is the different lipoproteins?

Back 111

Chylomicrons

VLDL

LDL

HDL

Front 112

What regulates the cholesterol synthesis?

Back 112

Activators: insulin

Inhibitors: glucagon, cholesterol, metabolites

Front 113

What are the fates of cholesterol?

Back 113

Front 114

Propionemia (propionic acidemia)

Back 114

Deficiency in the enzyme propionyl-CoA carboxylase, inhibiting the conversion of propionyl-CoA to D-methylmalonyl CoA.

Front 115

Methylmalonyl-uria

Back 115

Deficiency of the enzyme methylmalonyl-CoA epimerase, inhibiting D-methylmalonyl CoA to L-methylmalonyl CoA.

Front 116

What are the fates for the amino group and the carbon skeleton of an amino acid?

Back 116

Amino group (NH4+): biosynthesis of amino acids and nucleotides, urea cycle

Carbon skeleton: citric acid cycle

Front 117

What are the transporters of NH4+ from amin-acids to urea cycle?

Back 117

Glutamate and glutamine

The amino group is transferred through transamination.

Front 118

How is the transamination reactions?

Back 118

Alfa-ketogluatarate + NH4+ --> glutamate.

Glutamate + NH4+ --> glutamine.

An amino acid without NH4+ = alfa-keto acid.

The enzyme for the reaction is aminotransferase which requires PLP as a cofactor.

Examples: alanine aminotransferase (ALAT) and aspartate aminotransferase (ASAT).

Front 119

What is oxidative deamination?

Back 119

The release of NH4+ from glutamate, forming alfa-ketoglutarate. The enzyme for this reaction is glutamate dehydrogenase, which is the only enzyme that use either NAD+/NADP+.

Glutamate dehydrogenase is stimulated by ADP (GDP) and inhibited by GTP (ATP).

Front 120

What is transdeamination?

Back 120

Transamination + oxidative deamination = transdeamination

Front 121

What are the sources of NH4+ in the liver?

Back 121

- Amino acids from ingested proteins

- Alanine from muscle (glucose alanine cycle)

- Glutamine from muscle and other tissues (brain)

Front 122

What are the sources of ammonia NH3 in the urea cycle?

Back 122

- Amino acid degradation in every organ (especially in the liver and muscle)

- Ammonia secretion in kidney tubule from glutamine

- Nucleotide degradation (pyrimidine)

- Intestinal bacteria produce it from amino acids and urea

Front 123

What is the problem with ammonia?

Back 123

Ammonia is very toxic. It is quickly protonated to NH4+ in mitochondrial matrix and converted to urea, which is excreted in the kidney.

If the blood ammonium level increase it can cause cerebral edema and increased cranial pressure.

Front 124

Which enzymes of the urea cycle is located in mitochondria and which is located in the cytosol?

Back 124

Mitochondria: Carbamoyl phosphate synthetase I and ornithine transcarbamoylase

Cytosol: argininosuccinate synthetase, argininosuccinase (argininosuccinate lysase and arginase.

Front 125

Which metabolic intermediates are common between citric acid cycle and urea cycle?

Back 125

Aspartate, fumarate and malate.

Front 126

How is the urea cycle regulated? (short term and long term)

Back 126

Long term: Regulation of the rates of the synthesis (transcriptional regulation) of the 4 urea cycle enzymes and carbamoyl phosphate synthetase I.

Short term: Allosterically activation. Arginine stimulates the synthesis of N-acetylglutamate by N-acetylglutamate synthase. N-acetylglutamate stimulates the formation of carbamoyl phosphate by carbamoyl phosphate synthetase I.

Front 127

What are the difference between ketogenic and glycogenic amino acids?

Back 127

Ketogenic: produce ketone bodies in the liver

Glucogenic: produce glucose and glycogen

Mixed: both ketogenic and glucogenic

Front 128

Which amino acids are glucogenic?

Back 128

Aspargine

Aspartate

Methionine

Valine

Arginine

Glutamine

Glutmate

Hisitidine

Proline

They can become either pyruvate or oxaloacetate --> glucose

Front 129

What are the purely ketogenic amino acids?

Back 129

Leucine and lysine

--> Acetyl-Coa --> ketone bodies or citrate

Front 130

How is the enzyme glutamine synthetase regulated? (allosteric and covalent)

Back 130

Allosteric regulation: Each inhibitor produce partial inhibition, all 8 inhibitors together shut down the enzyme.

1. Glycine

2. Alanine

3. Glucosamine-6-phosphate

4. Histidine

5. CTP

6. Carbamoyl phosphate

7. Tryptophan

8. AMP

Covalent regulation: adenylation --> inactive

- Adenylation = (AMP) molecule is covalently attached to a protein side chain

- Adenylation stimulated by: glutamine, Pi

- Deadenylation stimulated by: ATP, alfa-ketoglutarate

Front 131

What is the most important antioxidant in RBC and what is the active amino acid making the anti oxidation effect?

Back 131

Gluthathione

Antioxidation effect: cysteine

It protects proteins for oxidation in erythrocytes. Removes toxic peroxide formed during growth and aerobic metabolism: glutathione peroxidase reaction.

Produced form glutamate, glycine and cysteine.

Front 132

What neurotransmitters is produced from the amino acids tyrosine, glutamate, histidine, tryptophan, methionine, arginine respectively?

Back 132

Tyrosine: dopa, dopamine, norepinephrine, epinephrine.

Glutamate: GABA (inhibitory neurotransmitter)

Histidine: histamine (vasodilator, released in allergic response, stimulates acid secretion in the stomach)

Tryptophan: serotonin

Methionine: spermine, spermidine (involved in DNA packaging)

Arginine: NO (important in neurotransmission, blood clotting and blood pressure control = vasodilator)

Front 133

The glucose-alanine cycle

Back 133

In the muscle, muscle protein is degraded to amino acids which inturn gives NH4+.

In the alanine cycle we can transport both NH4 and pyruvate to the liver by alanine aminotransferase, which transfer the amino group to pyruvate and form alanine. Alanine is transported in the blood. NH4 enters urea cycle, and pyruvate enters gluconeogenesis.

Front 134

Why is the overall energetic cost of urea synthesis is reduced?

Back 134

Because 1 NADH is formed in the malate dehydrogenase reaction (aspartate-argininisuccinate shunt).

Front 135

What is common between activation of fatty acids and activation of amino acids?

Back 135

Both need energy. They uses ATP which are converted to AMP + PPi.

Front 136

4 possible fates of fatty acids in the liver

Back 136

1. Free fatty acids

2. Beta-oxidation --> Acetyl CoA

Acetyl-CoA:

3. Cholesterol synthesis

4. Ketone body synthesis

5. Citric acid cycle

6. Storage as lipids

7. lipoproteins

Front 137

How many CO2 molecules are produced form one glucose molecule, what are the reactions producing those CO2?

Back 137

6 CO2 molecules

- Pyryvate dehydrogenase complex reaction

- Isocitrate dehydrogenase reaction

- Alfa-ketoglutarate dehydrogenase complex reaction

Front 138

What is the biological role of creatine and carnitine, ans what enzymes catalyzes them?

Back 138

Creatine: phosphocreatine is an energy reservoir in skeletal muscle during light activity or rest. Can rapidly regenerate ATP from ADP

Enzyme: Creatine kinase

Creatine + ATP <––> phospocreatine + ADP

Carnitine: transport long-chain fatty acids into the mitochondrion and regulate the intramitochondrial ratio of Acyl-CoA to free CoA.

Carnitine acyltransferase: carnitine + acyl-CoA <--> Acyl-carnitine

Front 139

What is the role of DNA-dependent RNA polymerase?

Back 139

An enzyme that produces primary transcript RNA. RNA polymerase is necessary for constructing RNA chains using DNA genes as templates, a process called transcription.

Front 140

What is the role of RNA-dependent RNA polymerase?

Back 140

RNA-dependent RNA polymerase or RNA replicase, is an enzyme that catalyzes the replication of RNA from an RNA template.

Front 141

Name the substrates and the products of the light reaction of photosynthesis

Back 141

2H2O + 2NADP+ ---> O2 2NADPH + 2H+

Front 142

Write with structures the reaction where an inhibitory neurotransmitter is produced from anamino acid directly.

Back 142

Glutamate decarboxylase reaction.

Front 143

What are the small RNAs other than microRNA that have a role in splicing and rRNA maturation respectively?

Back 143

Splicing: snRNA (small nuclear) - part of the spliceosome.

Maturation of rRNA: snoRNA (small nucleolar)

Front 144

What is called the secondary genetic code?

Back 144

= proofreading activity

Amino acid tRNA synthetase and tRNA interaction will recognize the tRNA that belongs to which amino acid. Get right anticodon for the right amino acid.

Front 145

Namea cell type that does not express MHC I on its surface.

Back 145

RBC and neurons only

Front 146

What can happen to glucose-6-phosphate in the liver?

Back 146

1. Glycolysis: glucophospho isomerase (energy production)

2. Gluconeogenesis: glucose 6-phosphatase (remove P toincrease blood sugar concentration)

3. Pentosephosphate pathway: Glucose 6-phosphatedehydrogenase (Ribose and NADPH production)

4. Glycogen synthesis: phosphoglucomutase (glycogen storage)

Front 147

Which transcription factor is the most important regulator in the expression of erythropoietin?

Back 147

HIF1 α (Hypoxia-inducible factor 1, α unit) --> Erythropoietin --> RBC production (since oxygen levelaccommodate to it)

Front 148

How to calculate the maximum amount of ATP produced from fatty acid degradation to CO2 and H2O?

Back 148

1. Number of Carbons/2 = Number of Acetyl CoA formed

2. Number of rounds in the Beta-oxidation necessary for converting the whole fatty acid to Acetyl Co A units = Number of Acetyl CoA - 1 = NADH and FADH2

3. NADH yields 2.5 ATP and each FADH2 yields 1.5 ATP. Multiply the number of rounds with 4.

4. Multiply the number of Acetyl CoA times 10 (10 ATP in each round of citric acid cycle)

5. Minus two ATP that were used for the activation of the fatty Acid.

Front 149

Why is it advantageous for the long fasting man that his brain is able to utilize ketone bodies (produced by the liver) as a fuel?

Back 149

Ketone bodies are produced from fat, converted to acetyl-CoA and then transported to the brain where it is used for energy. This prevent amino acid degradation, ketone bodies is used instead.

Front 150

4 factors/accommodations for transport ofGlc-6-P out of cell as free glucose

Back 150

1. High glucagon levels = low glucose levels in the blood

2. Glucose-6-phosphatase enzyme (only in the liver) - covert glc-6-P --> glucose

3. GLUT7 transporter (transport glucose from ER to cytosol

4. GLUT2 transporter (release glucose to the bloodstream)

Front 151

4 enzymes that release ammonia (NH3) directly

Back 151

Glutamate dehydrogenase

Glutaminase

Serine dehydratase

Adenosine deaminase

Front 152

Which immunoglobulin participate in the fetus passive immune system. Why?

Back 152

Passive immunity = when maternal antibodies are transferred to the fetus through the placenta.

IgG is the only immunoglobulin that can pass through the placenta. It protect against bacterial and viral infections in fetuses.

Front 153

Name 3 reactions in the animal tissue as possible sources of NADPH.

Back 153

Malic enzyme: malate <--> pyruvate

Glucose-6-phosphate dehydrogenase: glc-6-P <--> 6-phosphoglucono lactone

6-phosphogluconate dehydrogenase: 6-phosphogluconate --> ribulose-5-P

Front 154

Which mitochondrial enzymes are required during conversion of glucose to fatty acid?

Back 154

Pyruvat-Dehydrogenase-complex

Citrat-Synthase

Front 155

What does processivity mean, in relation to polymerases?

Back 155

Nucleotides added before the polymerase dissociates.

Polymerase I: 3-200

Polymerase II: 1500

Polymerase III: > 500 000

Front 156

What is the Shine-Dalgarno sequence and what is its biological role?

Back 156

Ribosomal binding site in the mRNA, generally located 8 basepairs upstreams for the AUG start codon.

Front 157

List hormone-familiesthat have nuclear receptors.

Back 157

Retinoic acid

Vitamin D

Thyroid

Steriod

Front 158

Which catalytic function is missing in retroviral reverse-transcriptase compared to human and E-coli DNA polymerase?

Back 158

Proofreading action. It is not able to do repair on the template, and mutations are very common (may cause immunity against drugs).

Front 159

Name two metabolic pathwayswhich take place partially in the mitochondria and partially in the cytosol.

Back 159

Gluconeogenesis

Urea cycle

Front 160

Possible Fates of amino acids in the liver

Back 160

1. Liver proteins

2. Nucleotides

3. Hormones

4. Porphorins

5. Urea Cycle

6. Gluconeogenesis

7. Acetyl-CoA:

TCA cycle

Fatty Acids

Front 161

By what mechanism can a G protein coupled hormone receptor regulate gene expression?

Back 161

G protein --> Adenylate Cyclase --> cAMP --> PKA

Front 162

What are the modifications on individual amino acids in posttranslational modification?

Back 162

Phosphorylation, carboxylation, methylation, sulfation, hydroxylation on the side chains.

Front 163

What are the different posttranslational modifications in protein synthesis?

Back 163

1. Modifications on both terminal ends

2. Loss of singal sequences

3. Modifications of individual amino acids

4. Glycosylation: attachment of carbohydrate side chains

5. Acylation: prenylation and farnesylation or

acetylation/deacetylation

6. Addition of prosthetic groups

7. Proteolytic processing

8. Disulfide crosslink formation

Front 164

What is the function of dolichol in post translational modification of proteins?

Back 164

It has an isoprene structure that is important in the glycosylation of proteins.

Front 165

Put in order of highest protein content of lipoproteins.

Back 165

HDL > LDL > IDL > VLDL > chylomicron

Front 166

Put in order of highest cholesterol content of lipoproteins.

Back 166

LDL > HDL > IDL > VLDL >chylomicrons

Front 167

What is the biological role of the reaction catalyzed by cytochrome P450?

Back 167

It detoxifies the body of drugs and toxins by hydroxylation.

Front 168

Name 5 types of antibodies/immunoglobulins found in humans.

Back 168

IgM, A, D, G,E.

Secreted form B cells in bone marrow.

Bind bacteria, viruses or large foreign molecules.

Front 169

Which antibody is mainly involved in allergic reactions?

Back 169

IgE

Front 170

List 3 differences between DNA and RNA polymerases.

Back 170

1. RNA polymerase does not need a primer

2. RNA polymerase has no 3’->5’ exonuclease activity

3. No proofreading

Front 171

What distinguishes the newly synthesized DNA strand from thetemplate?

Back 171

The template ismethylated.

Front 172

What is the role MutH/MutS/MutL?

Back 172

They are the main components of methyl directed mismatch repair. They winds up the DNA molecule.

Front 173

Name the factors responsible for promotor recognition inprokaryotes and eukaryotes.

Back 173

Prokaryotes:Sigma Factor

Eukaryotes:TATA binding protein

Front 174

What are the heme containing complexes of the respiratory chain?

Back 174

Complex IV

Cytochrome C

Complex III

Front 175

What is an allosteric inhibitor of carnitine acyl transferase?

Back 175

Malonyl-CoA

Front 176

In which glycolytic reaction is a C-C bond broken?

Back 176

Aldolase reaction

Fructose-1,6-bisphosphate <--> dihydroxyacetonephosphate + glyceraldehydphosphate

Front 177

Which enzyme enables yeast to synthesize glucose from acetyl-CoA

Back 177

Isocitrate lyase

Malate synthase

Glyoxylate cycle

Front 178

Name the 4 vitamins that givecofactors participating in alpha-ketoglutarate dehydrogenase reaction.

Back 178

TPP (B1) -> Thiamine

FAD (B2) -> Riboflavin

NAD (B3) -> Niacin

CoA-SH (B5) -> Pantothenic acid

Front 179

The enzyme in the oxidative phase of the pentose phosphate pathway

Back 179

Glucose-6-phosphate dehydrogenase

Lactonase

6-phosphogluconate dehydrogenase

Phosphopentose isomerase

Front 180

When is the non-oxidative phase in the pentose phosphate pathway active?

Back 180

In tissues which primarily require NADPH, pentose phosphates will be recycled back into glucose-6-phosphate in a series of rearrangements of the carbonskeletons .

Enzymes: Transketolase and transaldolase

Front 181

What are 4 fates of glucose-6-phosphate in the pentose phosphate pathway?

Back 181

1. Ribose-5-phosphate is needed:

Glc-6-P --> Frc-6-P --> ribose-5-p

Glyceraldehyde-3-P --> ribose-5-P

2. Ribose-5-phosphate and NADPH is needed:

Glc-6-P --> Ribulose-5-P + 2NADPH --> Ribose-5-P

3. NADPH needed:

Ribulose-5-P produced from Glc-6-P, but recycled. Prod NADPH.

4. NADPH and ATP needed:

Ribulose-5-P + NADPH is first made, then ribose-5-P is sent into glycolysis via fructose-6-p and glyceraldehyde-3-p, where ATP is produced.

Front 182

What are the enzyme reactions in the gluconeogenesis which are irreversible and different from the glycolysis?

Back 182

Pyruvate carboxylase

PEP carboxykinase

Fructose 1,6biphosphatase

Glucose 6 phosphatase

Front 183

What is the enzyme in the gluconeogenesis, found in both mitochondria and cytosol, and why is this enzyme important?

Back 183

Mitochondrial malate dehydrogenase and cytosolic malate dehydrogenase.

Pyruvate is converted to oxaloacetate by pyruvate carboxylase. Oxaloacetate can't pass the mitochondrial membrane, and is therefore converted to malate by mitochondrial malate dehydrogenase. Malate is transported into cytosol where it is converted back to oxaloacetate by cytosolic malate dehydrogenase

Front 184

What are the different transcriptional regulations of gluconeogenesis and glycolysis?

Back 184

SREBP-1 (sterol regulatory element binding proteins)

CREB (cAMP response element binding protein)

FOXO1 (forkhead box other)

ChREBP (carbohydrate response element binding protein)

Front 185

How does SREBP-1c regulate gluconeogenesis and glycolysis?

Back 185

SREBP-1c = sterol regulatory element binding proteins

Synthesis is increased by insulin and decreased by glucagon.

SREBP-1c will increase synthesis of: Hexokinase IV, pyruvate kinase, lipoprotein lipase, acetyl-CoA carboxylase, fatty acid synthase complex.

SREBP-1c will suppress synthesis of: PEP carboxykinase, FBPase-1, glucose 6-phosphatase (gluconeogenesis).

Front 186

How does CREB regulate gluconeogenesis and glycolysis?

Back 186

CREB = cAMP response element binding protein

Synthesis is increased by glucagon via cAMP.

Increases synthesis of PEP carboxykinase and glucose-6-phosphatase (stimulates gluconeogenesis)

Front 187

How does FOXO1 regulate gluconeogenesis and glycolysis?

Back 187

Insulin will have the effect of turning off expression of the genes. Insulin will activate a signalling cascade, which leads to activation of PKB. PKB will phosphorylate FOXO1 in cytosol. FOXO1 will be attached t ubiquitin, which will mark it for destruction via proteasome. FOXO1 which remains dephorphorylated can enter the nucleus and attach to DNA to trigger transcription of it's associated genes.

It increases synthesis of gluconeogenetic enzymes.

It supresses synthesis of glycolytic enzymes, pentose phosphate pathway enzymes and triacylglycerol synthetic enzymes.

Front 188

How does chREBP regulate gluconeogenesis and glycolysis?

Back 188

ChREBP = carbohydrate response element binding protein

ChREBP is inactive located in the cytosol when it is phosphorylated (2x), and cant move into nucleus. PP2A dephosphorylates it, allowing it to enter nucleus. In nucleus a second dephosphorylation by PP2A. This allows it to be associated with mix. ChREBP-Mix complex will bind to a carbohydrate response element, and stimulate transcription.

PP2A is allosterically activated by xylulose-5-phosphate. Xylulose-5-phosphate is a signal that other pathways which utilize glucose, has enough substrate.

ChREBP will therefore turn on synthesis of several enzymes: Pyruvate kinase, fatty acid synthase and acetyl-CoA carboxylase

Front 189

How is GSK-3 regulated?

Back 189

GSK-3 phosphorylates glycogen synthase b --> inhibiting glycogen synthesis. It is Inhibited by insulin.

GSK-3 requires prior phosphorylation or priming from casein kinase II.

Insulin will trigger activation of glycogen synthase a by blocking the activity of GSK3, and activating PP1 in muscles. Insulin will phosphorylate GSK3 via PKB/PKA.

Front 190

What enzyme can remove phosphoryl groups from all three of the enzymes phosphorylated in response to glucagon in liver and epinephrine in muscle/liver? How is it regulated?

Back 190

PP1 can remove phosphate groups from phosphorylase kinase, glycogen phosphorylase and glycogen synthase.

PP1 is not found in free form, but tightly bound to its traget protein by glycogen-targeting proteins.

Bind glycogen, each of the three enzymesRegulated- Positive allosteric regulation by glucose-6-phosphate- Negative covalent phosphorylation by PKA

Front 191

What are the possible pathways in enzyme regulation and degradation? (10)

Back 191

1. Extracellular signal

- Hormonal- neural- growth factors

2. Transcription of specific gene(s)

3. mRNA degradation

4. mRNA translation on ribosome

5. Protein degradation

- Tagged by ubiquitin for degradation by proeasomes

6. Enzyme sequestered in subcellular organelle

7. Enzyme binding substrate

8. Enzyme binds ligand (allosteric effect)

9. Enzyme undergoes phosphorylation/dephosphorylation

10. Enzymes combines with regulatory protein

Front 192

What are the steps of fatty acid synthesis, which enzymes, cofactors and products do we find?

Back 192

Before fatty acid synthesis we must activate Acetyl-CoA + ATP + HCO3- --> malonyl-CoA

Step 1 - Condensation

- Ketoacyl synthase

- Condensates the substrates, creating acetoacetyl-ACP

- CO2 is released

Step 2 - Reduction

- Ketoacyl reductase reduces NADPH + H --> NADP+

- D-B-hydroxybutyryl-ACP is formed

Step 3 - Dehydration

- Hydroxyoacyl dehydratase removes water from the substrate

Step 4 - Reduction

- Enoyl reductase reduces NADPH+H -> NADP+

- Double bond is saturated

-Saturated acyl group is formed, lengthened by two carbons

Front 193

What are the enzyme components of fatty acid synthase?

Back 193

8 enzymes in a complex

4 basic enzymes:

- Ketoacyl synthase

- Ketoacyl reductase

- Hydroxyacyl dehydratase

- Enoyl reductase

4 other:

- Acetyl carrier protein (ACP)

- Acetyl-CoA-ACP acyltransferase (AT)

- Malonyl-CoA-ACP acyltransferase (MT)

- Palmitate deacylase (PD)

Front 194

What is mechanism of fatty acid elongation in animal cells?

Back 194

Takes place in ER and mitochondria.

Palmitate is the precursor for most longer fatty acids. Similar mechanism as fatty acid synthesis, but with other enzymes, and using CoA instead of ACP.

Fatty acids are elongated on the head.

Elongation starts with donation of carbons by malonyl-CoA, thhen reduction, dehydration and reduction

Front 195

What is the mechanism of desaturation in vertebrates?

Back 195

Happens in smooth ER.

Fatty acid desaturation is needed for cell membrane fluidity in different temperatures. Double bond introduced via an oxidative reaction by fatty acyl-CoA desaturase.

During this process 2 different substrates will at the same time undergo electron oxidations.

- Electrons will flow via cytochrome and cytochrome reductas.

1. NADPH will give its electrons to cytochrome reductase - FAD --> FADH2

2. Cytochrome reductase (FADH2) will give it's electrons to cytochrome - Fe3+ -> Fe 2+

3. Cytochrome (Fe2+) will give them on to the fatty acid

Front 196

How can glycerol-3-phosphate be synthesized in liver and adipose tissue?

Back 196

In liver:

- Glycerol kinase

- Glycerol-3-phosphate dehydrogenase

In adipocytes:

- Glycerol-3-phosphate dehydrogenase

Front 197

What are the different head groups for phosphatidic acid? what else can phosphatic acid produce?

Back 197

Head groups can be ethanolamine, serine, inostiol, choline.

Triacylglycerol can be produced from phosphatidic acid

- Phosphatidic acid phosphatase (--> 1,2-Diacylglycerol)

- Acyl transferase (--> triacylglycerol)

Front 198

How is lipid synthesis regulated?

Back 198

Insulin

Favors synthesis of both acetyl-CoA (--> ketone bodies) and fatty acids (--> triacylglycerol synthesis)

Front 199

Synthesis of triacylglyceride

Back 199

1. Production of glycerol-phosphate

- Either via glycerol-3-phosphate (liver and fat) or glycerol kinase (liver)

2. Production of phosphatidic acid

- Acyl transferase twice

3. Production triacylglycerols and glycerophospholipids

- Phosphatidic acid phosphatase + acyl transferase --> triacylglycerol

Attachment of head group -> glycerophospholipids

Front 200

What is steps in the glyceroneogenesis?

Back 200

A shortened version of gluconeogenesis

1. Pyruvate

- Pyruvate carboxylase

2. Oxaloacetate

- PEP carboxykinase

3. Phosphoenolpyruvate

- Multistep

4. Dihydroxyacetone phosphate

- Glycerol-3-phosphate dehydrogenase

5. Glycerol-3-phosphate

6. Triacylglycerol synthesis

Front 201

What is the role of glyceroneogenesis?

Back 201

Adipose tissue is coupled with reesterification of free fatty acids to control the rate of fatty acid release in blood.

In fasting humans, it supports the synthesis of glycerol-3-P enough to account for 65% of fatty acid reesterification to triacylglycerol.

Front 202

How is the glyceroneogenesis regulated?

Back 202

Glucocorticoid hormone

- Stimulates glycerneogenesis in liver

- Inhibits glycerneogenesis in adipocytes

Thialozolidine

- Increases glyceroneogenesis --> increasing resynthesis of triacylglycerol in adipose tissue --> reduced amount of free fatty acid in blood

- Treats type II diabetes

Front 203

What are the two strategies for synthesizing complex lipids?

Back 203

Strategy 1:

Diacylglycerol activated with CDP and then add head group

- Remove CMP

Strategy 2:

Diacylglycerol + head group activated with CDP

- Remove CMP

Front 204

Which complex lipids use CDP-Diacylglycerol as precursors?

Back 204

Phosphatidylglycerol

- CDP-diacylglycerol + glycerol

Cardiolipin

- CDP-Diacylglycerol + phosohatidylglycerol

Phosphatidylinositol

- CDP-diacylglycerol + inostiol

Front 205

How do inositol phosphates function as intracellular signaling molecules?

Back 205

Splitting by phospholipase C

-Diacylglycerol --> DAG

- Inositol-1,4,5-triphosphate -> IP3

Splitting by phophatidyl-inositol 3 kinase (PI3K)

- Phosphatidyl-inositol 3,4,5 triphosphate or PIP3

Front 206

What are the roles of IP3 and DAG?

Back 206

IP3 and DAG both contribute to activation of protein kinase C (PKC), by raising cytosolic Ca2+ concentration and IP3 also activates Ca2+ dependent enzymes.

1. Hormone binding

2. GDP-GTP exchange on G protein

3. Activation of PLC by GTP-G

4. Cleavage of PIP2 to IP3 and DAG

5. Binding of IP3 to ER IP3 -receptor evoking Ca2+ release

6. DAG and Ca2+ activate PKC

7. PKC phosphorylates target proteins triggering hormone response

Front 207

How is acetoacetate activated for metabolism?

Back 207

Done by B-ketoacyl-Coa transferase

Succinate-CoA --> Succinate

Acetoacetate --> Acetoacetyl-CoA

Front 208

What are the steps of cholesterol synthesis?What is the rate determining step?

Back 208

1. Synthesis of mevalonate from HMG-CoA

- HMG-CoA reductase

- Rate determining step

2. Mevalonate is converted into a chain of activated isoprenes.

- ATP is utilized to attach phosphate groups activating isoprenes

- Geranyl pyrophosphate = 10 Carbons

3. After several steps squalene is formed = 30 carbons

- Precursor is farnesyl-pp = 15C

4. Cholesterol is formed from squalene after a sequence of reactions

- Cholesterol = 27 C

- One of the enzymes is cyclase

Front 209

The reactions of prenyl transferase

Back 209

Dimethylallyl-pp + isopenthenyl-pp --> geranyl-pp

Geranyl-pp + isopenthenyl-pp --> farnesyl-pp

Both reactions are head to tail condensations.

Front 210

What is the head to head reaction in cholesterol synthesis?

Back 210

2 farnesyl-pp --> squalene

Front 211

Esterification of cholesterol

Back 211

Cholesterol esters are formed in the liver by acyl-CoA-cholesterol acyl transferase (ACAT): Cholesterol + fatty acyl-CoA --> Cholesteryl ester + CoA

Cholesterol esters can also be formed from lecithin-cholesterol acyl transferase (LCAT): Cholesterol + Lecithine (phosphatidylcholine) --> Cholesteryl ester + Lysolecithine

Front 212

What is PPAR? What are the different types of PPARs and what are their function in lipid metabolism?

Back 212

PPAR - Peroxisome proliferator-activated receptors

- Nuclear receptors

- Transcription factor, regulating expression of genes

- Effect on lipid transport

PPARα:

- In liver, heart, muscle and kidney

- Regulates FA metabolism, transports HDL-cholesterol into the liver

PPARβ:

- In ubiquitous

- Keratinocyte differentiation, wound healing, mediating VLDL signaling of the macrophage

PPARγ:

- In adipocytes and macrophages

- Adipocyte differentiation, lipid storage, glucose homeostasis

Front 213

What are the 3 most common fates of cholesterol?

Back 213

Biliary cholesterol, bile acids and cholesterol esters.

All growing animal tissues need cholesterol for membrane synthesis, some organs (adrenal gland, gonads) use cholesterol as precursors for steroid hormone production.

Front 214

What are the 3 enzymes of the ATP-dependent pathway of protein degradation?

Back 214

E1: ubiquitin-activating enzyme

E2: ubiquitin-conjugating enzyme

E3: ubiquitin-protein ligase

Front 215

What is the role of PLP and what enzymes requires PLP?

Back 215

PLP is an intermediate amino group carrier - accepts and donates amino groups.

1. Transamination (aminotransferase)

2. Decarboxylation (decarboxylase)

3. Side chain cleavage (aldolase)

- Glycogen phosphorylase

- Aminotransferases (ALAT, ASAT)

- Cystathionine β-synthase

- Serine dehydratase

- Glutamate decarboxylase

- Histidine decarboxylase

Front 216

Where does the glutamine reaction take place?

Back 216

Liver, kidney, intestine

Mitochondria

Front 217

What are the mixed amino acids?

Back 217

Tryptophan

Phenylalanine

Tyrosine

Threonine

Isoleucine

Alanine

Cysteine

Glycine

Serine

Front 218

Which reaction can incorporate ammonia into organic compounds?

Back 218

1. Glutamine synthetase reaction:

- In all organisms

- Important regulatory point

2. Glutamate synthase reaction

- Only in plants and bacteria

Net ammonia incorporation is the result of the 2 reactions.

Front 219

What is nitrogen fixation?

Back 219

Reduction of N2 gas to ammonia:

N2 + 3 H2 ---> 2 NH3

The N-N triple bond is very stable. Therefore the activation energy of N-fixation is extremely high.

Nitrogen fixation is carried out by a highly conserved complex of proteins called the nitrogenase complex.

Hydrolysis of 16 ATP.

Overall equation:

N2 + 10H+ + 8e– + 16ATP --> 2NH4+ + 16ADP + 16Pi + H2

Front 220

Hyperammonia

Back 220

A typical result of urea cycle defects (UCDs) ishyperammonemia and/or the build-up of one or more ureacycle intermediates (depending on the missing enzyme).

Permanent activation of glutamate dehydrogenase also causeshyperammonemia (hyperinsulinism-hyperammonemiasyndrome).

Front 221

Hyperglycinemia

Back 221

Defect of the glycine cleavage enzyme.

Front 222

Write with structures the reaction that is defective in albinism.

Back 222

Defect of tyrosinase - melamine synthesis form trypsin --> lack of pigmentation: white hair and pink skin.

Front 223

What are the steps in the biosynthesis of heme?Where does the biosynthesis of heme in mammals take place and how is it regulated?

Back 223

1. Synthesis of δ-aminolevulinate

- From succinylCoA and glycine by δ-aminolevulinate synthase

2. Synthesis of porphyrins

- Chain of different reactions --> protoporphyrin

3. Synthesis of heme

- Protoporphyrin --> heme by ferrochelatase

Takes place in mitochondria and in the cytosol.

Heme is a feedback inhibitor.

Front 224

Degradation of heme

Back 224

Heme degradation protects cell from oxidative damage.

Heme oxygenase reaction:

Heme + 2O2 + NADPH + H+ --> Biliverdin + Fe2+ + CO + H2O + NADP+

- Fe2+ binds to ferritin

- CO binds to hemoglobin - toxic at high conc. and vasodilator at low conc.

- Biliverdin reductase reaction --> bilirubin, which binds to serum albumin. Important antioxidant in the blood.

Front 225

Aspartate-agininosuccinate shunt

Back 225

Argininosuccinate will form arginine and fumarate via the enzyme argininosuccinase. This fumarate can be converted to malate and enter the citric acid cycle. This connection is the aspartate-argininosuccinate shunt of citric acid cycle.

Oxaloacetate from citric acid cycle reacts with glutamate and form aspartate and alfa-ketoglutarate. Aspartate enter urea cycle and reacts with citrulline.

Front 226

What are the ATP dependent reactions of the urea cycle, and where do they happens?

Back 226

Carbamoyl phosphate synthase I

- Requires 2ATP

- NH3 reacts with bicarbonate to form carbamoyl phosphate which enters cycle

- Reaction takes place in the mitochondria

Argininosuccinate synthetase

- Requires ATP --> AMP

- Takes place in cytosol

- Aspartate enter the urea cycle from the citric acid cycle

Front 227

What are the two pathways to protein degradation?

Back 227

1. ATP-dependet pathway used for degradation of defective proteins, and those with short half-lives

- Involves ubiquitin, which becomes covalently linked to proeins slated for destruction via an ATP-dependent pathway

- Involves E1, E2, E3

- Ubiquinated proteins are degraded by proteasome

2. A second system is found in lysosomes. This recycles the amino acids of membrane proteins, extracellular proteins and those with longer half-lives.

Front 228

What is the effect of cholesterol entering the cell on cholesterol synthesis?

Back 228

1. Down regulation of receptor mediated endocytosis

2. Inhibition of cholesterol synthesis

3. Promotion of cholesteryl esters

4. Inhibition of endocytotic receptor synthesis

Front 229

What are some substrate-level phosphorylations?

Back 229

Glycolysis:

- Phosphoglycerate kinase

- Pyruvate kinase

Citric acid cycle:

- Succinyl-CoA synthetase

Front 230

What are the roles of nucelotides in cells?

Back 230

1. DNA and RNA precursors

2. Carrier of chemical energy (ATP and GTP)

3. Co-factor components (NAD, FAD, coenzyme A, S-adenosylmethionine)

4. Activated intermediates (UDP-glucose, CDP-diacylglycerol)

5. Cellular second messenger (cAMP, cGMP)

Front 231

What are the two ways of nucleotide synthesis?

Back 231

1. Salvage pathway

- Activated ribose (PRPP) + base --> nucleotide

- Recycles free bases and nucleotides released during nucleic acid breakdown

- Adenine + PRPP --> AMP + PPi

- Hypoxanthine + PRPP --> IMP + PPi

- Guanine + PRPP --> GMP + PPi

2. De novo pathway

- Activated ribose (PRPP) + amino acids + ATP + CO2 + NH3 --> Nucleotide

Front 232

What are the common motives of purine and pyrimidine synthesis?

Back 232

1. Uses 5- phosphoribosyl-1- pyrophosphate (PPRP)

2. Uses amino acids-

- Glycine --> purine

- Aspartate --> - pyrmidine

3. N donor: glutamine (aspartate - purine)

Front 233

Why can nucleotide synthesis limit rate of DNA replication and transcription?

Back 233

Cellular pool of nucleotides i 1% or less of the amounts required to synthesize the cell's DNA.

Front 234

How is purine nucleotide biosynthesis regulated?

Back 234

It's regulated by feedback inhibition.It is regulated in 4 steps by the end-products.

1. AMP, GMP and IMP will inhibit the first reaction- Glutamine-PRPP amidotransferase: PRPP --> 5-phosphoribosylamine

2. The end-products will inhibit their own synthesis from IMP.

- AMP will inhibit adenylosuccinate synthetase

- GMP will inhibit IMP dehydrogenase

3. Reciprocal regulation

- Balance between AMP and GMP

4. AMP from end-product will be phosphorylated to ADP, and ADP will inhibit ribose phosphate pyrophosphokinase (PRPP synthetase): ribose-5-phosphate --> PRPP

Front 235

What are the different types of purines and pyrimidines?

Back 235

Purines: 2 rings

- Adenine and guanine

Pyrimidine: 1 ring

- Cytosine, Thymine (DNA), Uracil (RNA)

Front 236

What type of enzymes are used in the nucleotide synthesis?

Back 236

Large, multienzyme complex in the cell

Front 237

What are pyrimidine nucleotides made from?

Back 237

Made from aspartate, carbamoyl phosphate and PRPP.

Front 238

What are purine nucleotides made from?

Back 238

Made from CO2, glycine, formate, glutamine and aspartate.

Front 239

How is pyrimidine biosynthesis regulated?

Back 239

Regulated by feedback inhibition (negative feedback) of the end-product.

- Cytidine-5-triphosphate (CTP) inhibits aspartate transcarbamoylase allosterically.

- ATP is a positive modulator of the same enzyme. It prevents change induced by CTP.

Front 240

What does degradation of purines and pyrimidines give?

Back 240

Purine --> uric acid

Pyrimidine --> urea

Front 241

Adenosine deaminase deficiency

Back 241

Causes immunodeficiency

- T and B wont properly develop

Front 242

Lesch-Nyhan syndrome

Back 242

Brain highly depends on salvage pathways.

Without salvage pathway, PRPP levels rise.

This syndrome prevents salvage pathway of guanine.

Causes:

- Purine overproduction

- High levels of uric acid

- Brain damage

Front 243

What are the different types of histones?

Back 243

H1, H2A, H2B, H3, H4

Front 244

What is the function of chromatin remodelling complex SWI/SNF?

Back 244

Dissociates DNA from the surface of nucleosomes, decondensing thechromatin and making the DNA more accessible to transcriptionfactors.

Front 245

What is the function of chromatin remodelling complex NURF?

Back 245

Activates RNA polymerase II thus participating in transcriptional activation.

Front 246

What is the function of chromatin remodelling complex INO80?

Back 246

Transcriptional activation, DNA repair, telomereregulation, chromosome segregation and DNA replication.

Front 247

What is the function of microRNA (miRNA)?

Back 247

Post-transcriptional regulators, silencing of many genes

22 nucleotide long RNA sequence

Front 248

What is a holoenzyme?

Back 248

A catalytically active enzyme together with its boundcoenzyme and/or metal ions

Front 249

What inhibits RNA polymerases in prokaryotes and eukaryotes respectively?

Back 249

- Actinomycin D: both pro- and eukaryoticRNA polymerase

- Rifampicin: prokaryotic RNA polymerase

- α-amanitin: eukaryotic RNA polymerase (Pol II, Pol III)

Front 250

Describe breifly mRNA processing

Back 250

1. Start with DNA strand

2. Transcription and 5´capping --> Primary mRNA transcript (contains 5´cap, exons and introns)

3. Spilcing, cleavage and polyadenylation --> mature mRNA (contains 5´cap and exons, no introns)

Front 251

What is the function of siRNA (small interfering)?

Back 251

Binds to the mRNA and silence it.

Front 252

What is the function of saRNA (small activating)?

Back 252

Induce gene activation (long lasting)

Front 253

What is the function of snRNA (small nuclear)?

Back 253

Processing of pre-mRNA in the nucleus.

Part of the spliceosome.

Front 254

What is the function of snoRNA (small nucleolar)?

Back 254

Guide chemical modifications of other RNAs (methylation or pseudouridylylation).

Front 255

What is the function of piRNA (piwi-interacting)?

Back 255

- Largest class of small RNAsin animal cells.

- Transcriptional gene silencing of retrotransposons in germline cells.

Front 256

What is the function of rasiRNA (repeat associated small interfering RNA)?

Back 256

- Establishes and maintaining heterochromatin structure.

- Control transcripts that emerge from repeat sequences

- Silencing transposons and retrotransposons.

Front 257

What is the function of tmRNA?

Back 257

- Rescues ribosomes (mRNA without stop codon).

- Recycles the stalled ribosome

- Facilitates degradation of non-normal mRNA.

Front 258

What is the function of qiRNA?

Back 258

- DNA damage induces its expression

- Role in DNA damage response: inhibiting protein translation

Front 259

What are the regulation factors of the ribosomal section of translation?

Back 259

eIF2, eIF4E, mTOR, antibiotics

Front 260

What is interferon control?

Back 260

Virally infected cells turn off translation to prevent spread of viruses.This is achieved using interferons (a cytokine). They induce RNA dependent protein kinase (PKR) that phosphorylates eIF-2 (inactivation), which reduce translation. PKR also indirectly induce RNase L (and thus mRNA degradation.

Front 261

What are the protein factor required for initiation of translation in bacteria and eukaryotes respectively?

Back 261

Bacteria: IF-1, IF-2, IF-3

Eukaryotes: elF2, elF2B, elF3, elF4A, elF4B, elF4E, elF4G, elF5, elF6

Front 262

What is special with mitochondria replication, transcription and synthesis?

Back 262

- Happens in the matrix

- Replication not limited to S-phase

- Individual mtDNAs replicate randomly (some more than others)

- Double stranded ring, nucleoid

- No histones, no introns, polycistronic transcription (many genes)

- Only 22 tRNA for protein synthesis

- Reduced accuracy: 10x greater rate of nucleotide substitution

- Mitochondrial mRNA: no 5 ́cap, but a poly-A at 3 ́end added post-transcriptionally

- mtDNA is inherited maternally, non-mendelian

Front 263

What are the effects of insulin on blood glucose, uptake of glucose and storage ad triacylglycerols and glycogen?

Back 263

Increase:

- Glucose uptake (in muscle, adipose tissue and liver)

- Glycogen synthesis (liver and muscle)

- Glycolysis, acetyl- CoA production (liver and muscle)

- Fatty acid synthesis (liver)

- Triacylglycerol synthesis (adipose tissue)

Decrease:

- Glycogen breakdown (liver and muscle)

Front 264

What are the effects of glucagon on blood glucose, production and release of glucose by the liver?

Back 264

Increase:

- Glycogen breakdown

- Gluconeogenesis

- Fatty acid mobilization

- Ketogenesis

Decrease:

- Glycogen synthesis

- Glycolysis

Front 265

What does the theory of glucose fatty acid cycle state?

Back 265

If plasma glucose is decreased, fatty acids are mobilized from adipose tissues (fasting, effect of glucagon) and the increased fatty acid level will decrease glucose utilization, restoring glucose level and maintaining homeostasis.

Front 266

Arsenate poisining, and what is a reaction which can use arsenate?

Back 266

Arsenate (AsO4), is structurally and chemically similar to inorganic phosphate (Pi). This allows many enzymes, which require phosphate to use arsenate instead, making it very dangerous. Arsenate is very toxic to most organisms,

Glyceraldehyde-3-phosphate dehydrogenase. Will create 1-arseno-3-phosphoglycerate instead of 1,3-bisphosphoglycerate. No TCA and respiratory chain --> no ATP is produced --> no ATP is produced --> fatal

Front 267

How is isocitrate dehydrogenase regulated?

Back 267

Inhibited by ATP.

Activated by Ca2+ and ADP.

Front 268

How is a-ketoglutarate dehydrogenase complex regulated?

Back 268

Inhibited by succinyl-CoA (product), NADH

Activated by Ca2+

Front 269

How is glycogen-targeting protein, Gm regulated?

Back 269

Gm binds glycogen to enzymes, like PP1.

Gm can be phosphorylated at 2 different sites, which give different effects

- In response to epinephrine and insulin.

1. Insulin stimulated phosphorylation

- Phosphorylation at site 1

- Activates PP1, which dephosphorylates phosphorylase kinase, glycogen phosphorylase and glycogen synthase

- Insulin inhibit glycogen breakdown, and stimulate glycogen synthesis

2. Epinephrine stimulated phosphorylation

- Phosphorylation at site 2

- Dissociation from PP1, inactivating it

- Preventing access of PP1 to glycogen phosphorylase and synthase

- PP1 is also connected to phosphorylated inhibitor 1, inactivating it

- Epinephrine or glucagon will stimulate glycogen breakdown, and inhibit glycogen synthesis

Front 270

What are the names of the different complexes in the respiratory chain?

Back 270

Complex I = NADH dehydrogenase

Complex II = Succinate-dehydrogenase

Complex III = Ubiquinone-cytochrom-c- oxidoreductase

Complex IV = Cytochrome-oxidase

Front 271

4 fates of pyruvate in the liver

Back 271

1. Acetyl-CoA --> citric acid cycle = pyruvate dehydrogenase complex

2. Lactate (anaerobic conditions) = lactate dehydrogenase

3. Oxaloacetate (gluconeogenesis) = pyruvate carboxylase

4. Malate = malic enzyme

Front 272

Which amino acid and vitamin make up collagen?

Back 272

Glycine

Vitamin C

Front 273

What is the function of beta-arrestin?

Back 273

Acts as a cofactor in the beta-adrenergic receptor kinase (BARK) mediated desensitization of beta-adrenergic receptors.

Also function as a scaffold protein.

Front 274

Through which molecule is PKA, PKB, PKC and AMPK activated in each case?

Back 274

- epinephrine/glucagon --> cAMP --> PKA

- PDK-1 --> PKB

- DAG and IP3 --> increased cytosolic Ca2+ --> PKC

- High concentrations of AMP (stress, exercise), leptin (fasting) --> AMPK

Front 275

Name four basic mechanisms and molecular processes that guarantee the accuracy of translation.

Back 275

- Secondary genetic code

- Wobble formation (first two bases in codon has strong base pairing)

- Proofreading

- Ribosomal with aminoacyl t-RNA synthase

Front 276

What is replisome and what are the structure?

Back 276

The entire complexresponsible for coordinated DNA synthesis at a replication fork. The replisome promotes rapid DNA synthesis.

SSB - binds to single stranded DNA and prevent it from re-forming a double stranded structure.

Helicase - used to separate strands of double stranded DNA molecule

Primase - catalyze synthesis of primer

DNA polymerase - synthesize DNA

DNA ligase - facilitates the joining of DNA strands together

DNA gyrase (topoisomerase II) - prevent supercoiling ahead of replication fork

Front 277

Give 3 hormones that are phosphorylated by glucagon indirectly via cAMP?

Back 277

- Phosphofructokinas

- Pyruvate dehydrogenase complex

- Glycogen phosphorylase kinase

Front 278

Function of mTOR, how it enables translation and moleculesinvolved. Function of elF4E.

Back 278

mTOR functions as a serine/threonine protein kinase that regulates cell growth, cell proliferation, cell motility, cell survival, protein synthesis, autophagy, and transcription.

- mTOR is a protein kinase activated by Akt/PKB.

- It phosphorylates a protein (4E-BP) that block elF-4E, thus suppressing the formation of the complete initiation complex.

- When the block comes off --> elF4E can bind to 5 ́Cap of mRNA --> initiation of translation.

- Too high eIF-4E activity can lead to tumorigenesis.

Front 279

What makes elF4E so important in regulation of gene expression?

Back 279

Since eIF-4E has the lowest cellular level of all eIFs, it is an efficient regulation pointfor the whole translation process.

Front 280

How is elF-4E regulated?

Back 280

Transcription

Phosphorylation

Inhibited by interactions with binding proteins

Front 281

Protein targeting

Back 281

Directs the structures to specific destinations by synthesizing a signal sequence of amino acids on the end.

Signal recognition particle binds to ribosome, and direct it to SRP receptor on ER.

- Binds GTP

Ribosome receptor and SRP receptor are found on the outside of ER.

On the inside peptide translocase complex is found.

The product is guided into the ER, and signal peptidase will cleave off the signal sequence.

Front 282

Definition of lipoproteins

Back 282

Large aggregates with non–covalent interactions between lipids and proteins.

Front 283

What is the general function of lipoproteins?

Back 283

Carry and transfer different types of lipids between organs and tissues.

Front 284

What is the structure of lipoprotiens?

Back 284

Core: Triacylglycerols, cholesteryl esters

Shell: Phospholipids, cholesterol, apo(lipo)proteins

The content and ratio between the different molecules varies in different types of lipoproteins.

The size differs betweeen the different types of lipoproteins.

Front 285

Put in order of highest triacylglycerol of lipoproteins.

Back 285

Chylomicron > VLDL > LDL > HDL

Front 286

Density of lipoproteins

Back 286

The density increases as the size decreases.
HDL > LDL > VLDL > Chylomicrons

Front 287

Apoproteins in the different lipoproteins

Back 287

IDL, LDL, VLDL: Apo B100
Chylomicrons: Apo B48
HDL: Apo A-I, A-II

Front 288

Transport of lipids

Back 288

Lipases cleave triacylglycerols to fatty acids and monoacylglycerols in the lumen, which are transported through the membrane. Then they are converted back to triacylglycerols in the mucosal cells. Then the triacylglycerols form chylomicrons together with other lipids and proteins. The chylomicrons are transported to the lymph system.

Front 289

Transport and properties of plasma lipoproteins

Back 289

- Chylomicron: hydrolysis by lipoprotein lipase.

- Chylomicron remnant: Receptor-mediated endocytosis by liver.

- VLDL: Hydrolysis by lipoprotein lipase.

- IDL (VLDL remnants): Receptor-mediated endocytosis by liver and conversion into LDL.

- LDL: Receptor-mediated endocytosis by liver and other tissues.

- HDL: Transfer of cholesterol esters to IDL and LDL.

Front 290

Energy sources for muscle contraction

Back 290

Light activity or rest: Fatty acids, ketone bodies, blood glucose


Heavy activity: muscle glycogen, phosphocreatine

Front 291

Energy sources for the brain

Back 291

Starvation: ketone bodies

Normal diet: glucose

NB: No glycogen storage in the brain!

When there is enough glucose in the blood the brain will only use glucose as an energy source.

The brain operates more efficiently during starvation, when the energy source is ketone bodies and not glucose.

Front 292

What is the normal range of blood glucose in human?

Back 292

60–90 mg/100 mL

Front 293

Hypothalamic regulation of food intake

Back 293

Hypothalamus secrete norepinephrine which is a signal for adipose tissue to secrete leptin into the blood. Leptin is a "satiety hormone" that regulates food intake.

Front 294

How is the short–term eating behavior regulated?

Back 294

Ghrelin

Front 295

Effects of adiponectin

Back 295

Stimulates AMPK

Muscle:
Increase fatty acid uptake, beta oxidation and glucose uptake

Liver:
Increase glycolysis, decrease gluconeogenesis and fatty acid synthesis.

Front 296

What are the main functions of the liver?

Back 296

- Synthesis (plasma proteins, sugars, clotting factors, urea, lipids, bile)

- Detoxification

- Excretion

- Storage (Glycogen, vitamins, Cu)

Front 297

What are the toxic compounds which need biotransformation (detoxification)?

Back 297

Compounds poorly soluble in water, biologically active and some toxic.

Front 298

What can failure of the detoxification system lead to?

Back 298

– Inflammatory conditions
– Rheumatoid Arthritis
– Parkinson’s
– Alzheimer’s
– Cancer
– ME

Front 299

What are the organs which process and eliminate waste?

Back 299

– Liver (most intensive site of detoxification)
– Intestines (second most intensive site)
– Kidneys
– Blood and bile
– Lungs

Front 300

Definition of biotransformation

Back 300

Biotransformation of drug is defined as the conversion from onechemical form to another. The term is used synonymously with metabolism.

E.g. Active drug (salicylic acid) --> inactive drug (salicyluric acid)

Front 301

What are the parts (phases) of biotransformation?

Back 301

- Phase 1: Oxidation (P450), reduction or hydrolysis

- Phase 2:  Conjugation
(Glucuronidation, sulfation, glutathionconjugation, methylation)
Adds molecules to increase the solubility of the compound.

Front 302

What are the difference between microsomal and non–microsomal enzymes?

Back 302

Front 303

What does the cytochrome P450 enzyme system contain?

Back 303

Monooxigenase
650 isoenzyme
Electron donor: NADPH

Front 304

P450 gene family

Back 304

CYP1, CYP2, CYP3, CYP4


Individual distribution of the different types.

Front 305

What are the causes of alcohol consumption?

Back 305

– Primary cause of liver disease
– Can be toxic to brain, GI tract, and pancreas
– Abuse leads to nutrient deficiencies

Front 306

Pathway of alchohol

Back 306

1. Mouth and esophagus: alcohol is diluted by saliva before being swallowed. Some is immediately absorbed.

2. Stomach: more alcohol is absorbed here, irritating the lining of the stomach and increasing the acidity. Men have alcohol dehydrogenase in the stomach which lead to start of alcohol metabolism, but women does not have this enzyme in the stomach.

3. Small Intestine: any remaining alcohol is passed here and is the site of most alcohol absorption.

4. Bloodstream: alcohol quickly diffuses through the body, affecting almost all cells.

5. Brain: these cells are more susceptible because they are usually protected from toxic by blood-brain barrier.

6. Liver: blood alcohol is metabolized in two stages and then respired into CO2, H2O and fatty acids.

7. Excretion via urine, the lungs and sweat.

Front 307

What is special with the alcohol metabolism?

Back 307

There is no hormonal regulation of alcohol metabolism. What we consume will be absorbed.

Front 308

How is the alcohol processed in the liver?

Back 308

Alcohol is processed by the liver as it arrives from the bloodstream.

The liver produces enzymes called alcohol dehydrogenase (ADH).

ADH: ethanol + NAD+ <--> Acetaldehyde + NADH + H+

Acetaldehyde is more toxic than alcohol itself (can cause inflammation). Acetaldehyde is then converted into acetate by ALDH in the mitochondria.

ALDH: acetaldehyde + NAD+ --> acetate + NADH + H+

Acetate is digested into fatty acid, CO2 and H2O.

Fatty acids, when digested, create 7 calories per g alcohol.

Front 309

What are the three alcohol enzymes?

Back 309

The three enzymes which can convert alcohol to acetaldehyde are:
– Alcohol dehydrogenase (ADH) – cytosol
– Cytochrome P450 (CYP2E1) – microsomes
– Catalase – peroxisomes

These three enzymes are each found in different parts of the body and each of them handles the hydrogen atoms which are stripped off from the alcohol molecule in a different way.

Front 310

What are the metabolic consequences of increased NADH/NAD ratio?

Back 310

– Decreased gluconeogenesis (hypoglycemia)
– Increased lactate
– Decreased TCA cycle
– Inhibition of most oxidations that use liver NAD (inhibition of some drug and hormone metabolism)
– Decreased fatty acid oxidation
– Increased fatty acid synthesis

Front 311

Microsmal (cytochrome P450) oxidation of ethanol

Back 311

CH3CH2OH + O2 + NADPH + H––> NADP+ + CH3CHO + 2H2O

Front 312

Catalase–Dependent Oxidationof Ethanol

Back 312

CH3CH2OH + H2O2 ––> CH3CHO + 2H2O

Catalase, a heme enzyme, is found in the peroxisomal fraction of the cell. This is an important antioxidant enzymesince it normally catalyzes the removal of H2O2.
H2O2 + H2O2 ––> 2H2O + O2

The primary catalytic enzyme in the brain cells.

Front 313

What are the long term effects of excess alcohol consumption?

Back 313

- Tissue damage

- Liver damage

- Brain damage

- Weight gain

- Skin damage

Front 314

What are the most important trace elements in the body?

Back 314

Fe, Mn, Co, Cu, Zn, Mo, V, Cr, Ni, F, Si, Se, As

<0,01 % of the body weight

Front 315

What is the requirement and the minimum intake of iron per day? What is the body iron content

Back 315

Requirement: ~ 1–3 mg/day
Minimum intake: 5–20 mg/day

Body iron content: 3-4 g

Front 316

What are the iron containing proteins in humans?

Back 316

75% heme iron (hemoglobin, myoglobin, cytochromes, catalase, peroxidase, PG–synthase,NO synthase)

25 % non–heme iron (transferrin, ferritin, Fe–S proteins)

Front 317

How is the copper transported in the blood.

Back 317

Transported in blood by ceruloplasmin, albumin.

Front 318

Copper containing enzymes

Back 318

– Redoxenzymes
– Cytochrome oxidase (complex IV)
– Superoxide dismutase
– Hydroxylases (e.g dopamine–beta–hydroxylase)

Front 319

Which diseases do copper deficiency lead to?

Back 319

Wilson´s disease: Intracellular Cu deposition (liver, brain and kidney), low serum Cu and high urinary Cu, low ceruloplasmin. Cannot be cured, only treated by removal by complex formation (penicillamin).

Menke´s syndrome: disorder of cellular Cu uptake (deficiency of ATP7A membrane transporter).

Front 320

Which enzymes/molecules contains zinc?

Back 320

– DNA–RNA polymerase
– Zn–finger (DNA–binding domain of certain transcription factors)
– Alcohol dehydrogenase
– Proteases
– Carbonic anhydrase

Front 321

Where is manganese present?

Back 321

– Cofactor: oxidoreductases (e.g.. Xanthine oxidase), transferases, hydroxylases, lyases, isomerases, ligases, pyruvate carboxylase, arginase

- Retroviruses: HIV

- Glycogenin

- Photosynthesis

Front 322

What structures does RBC´s lack?

Back 322

Nucleus (DNA)
Mitochondira
ER, golgi, ribosomes

Front 323

What is the function of RBCs?

Back 323

Transport O2 and CO2, NO

Front 324

2,3–biphospho–glycerate

Back 324

Decrease the affinity of oxygen of hemoglobin (right shift).

Front 325

Structure of hemoglobin

Back 325

2 parts : heme +globin

Globin: four chains There are four types of chains; α, β, γ and δ. 2 alfa (chromosome 16) and 2 beta (11 chromosome) chains is the normal structure.

Heme: porphyrin ring with central iron. Iron is the site of attachment with O2.

Front 326

Adult hemoglobin vs fetus hemoglobin

Back 326

Adult (HbA): 2 alfa chains and 2 beta chains
Fetus (HbF): 2 alfa chains and 2 gamma chains

Front 327

Sickle cell disease

Back 327

– Homozygous for the abnormal gene that codes for Hb S.
– Hb S results from a substitution of valine for glutamic acid at the sixth position from the NH2 terminal end of the β chain.

Hb S: 2 alfa 2beta, 6Glu ––> Val

Cause the red cell to deform into the sickle shapeand reduce the cells ability to circulate. This leads to hypoxia,pain and infarction of organs.

Front 328

Hemoglobin C

Back 328

Found almost exclusively in Negro populations.

Hb C differs from normal Hb A by the single aminoacid substitution of lysine for glutamic acid in the sixthposition from the NH2 terminal end of the β chain.

Hb C: 2 alfa 2beta, 6Glu ––> Lys

Causes mild chronic haemolytic anaemia withassociated splenomegaly and abdominal discomfort.

Front 329

Functions of blood

Back 329

– Substance distribution
– Regulation of blood levels of particular

- Body protection

Front 330

What does blood transport?

Back 330

- Oxygen from the lungs and nutrients from the digestive tract

– Metabolic wastes from cells to the lungs andkidneys for elimination

- Hormones from endocrine glands to targetorgans

Front 331

Blood maintains

Back 331

- Appropriate body temperature by absorbing and distributing heat to other parts of the body

– Normal pH in body tissues using buffer systems

- Adequate fluid volume in the circulatorysystem

Front 332

What does blood prevent?

Back 332

Blood prevents blood loss by:
– Activating plasma proteins and platelets
– Initiating clot formation when a vessel is broken

Blood prevents infection by:
– Synthesizing and utilizing antibodies
– Activating complement proteins
– Activating WBCs to defend the body againstforeign invaders

Front 333

Average blood volume

Back 333

5–6 L for males
4–5 L for females (normovolemia)

Hypovolemia: low blood volume
Hypervolemia: high blood volume

Front 334

Viscosity, pH and osmolarity and salinity of blood

Back 334

– Viscosity (thickness): 4 – 5 (where water = 1)

– pH of blood is 7.35–7.45; x = 7.4

– Osmolarity = 300 mOsm or 0.3 Osm
This value reflects the concentration of solutes in the plasma.

– Salinity = 0.85%
Reflects the concentration of NaCl in the blood

Front 335

Blood plasma components

Back 335

Water = 90–92%

Proteins = 6–8%
– Albumins: maintain osmotic pressure of the blood
– Globulins: Alpha and beta globulins are used for transport purposes. Gamma globulins are the immunoglobulins (IgG, IgA, IgM, IgE, IgD)

- Fibronogen: clotting protein

– Organic nutrients: glucose, carbohydrates, amino acids

- Electrolytes: sodium, potassium, calcium, chloride, bicarbonate.

- Nonprotein nitrogenous substances: lactic acid, urea, creatinine.

- Respiratory gases: oxygen and carbon dioxide

Front 336

Prealbumin

Back 336

Prealbumin migrates faster than albumin in the classicelectrophoresis.

It is the transport protein for:
– Thyroid hormones
– Retinol (vitamin A)

Front 337

In which diseases are prealbumin decreased?

Back 337

Prealbumin is decreased in:
– Liver disease
– Nephrotic syndrome
– Acute phase inflammatory response
– Malnutrition

Front 338

Albuminuria

Back 338

When albumin is detected in urine. This is due to physiological or pathological conditions.

Front 339

What is the functions of albumin?

Back 339

1. Oncotic pressure:Albumin is responsible for ~80% of the plasma oncotic pressure.It is a major determinant of the distribution of fluids betweenintravascular and extravascular compartments.Hypoalbuminemia leads to edema.

2. Buffering

3. Transport:Many substances are transported in the blood bound to albumin.

Lipid-soluble substances; hormones (thyroid hormones and steroid hormones), calcium, drugs, free fatty acids (FFA) and bilirubin.

Front 340

alfa1–Antitrypsin

Back 340

Synthesized by the liver and macrophages

It is acute–phase protein in order to inhibit proteases.

Proteases arise from:
– Endogenous production : by digestive enzymes such as trypsin& chymotrypsin.
– Infection: protease release from bacteria and from leukocytes(inflammatory response)

Front 341

Acute Phase Proteins

Back 341

Produced after stress reactions, infection, inflammation , malignancy, trauma or major surgery. They are produced in response to humoral mediators which are produced by tissue macrophages, monocytes and endothelial cells in inflammation

– a1–Antitypsin
– Haptoglobin
– Ceruloplasmin
– Fibrinogen
– C–reactive protein

Front 342

Ceruloplasmin

Back 342

– Synthesized by the liver
– Contains over 90% of serum copper.
– It is important in acute phase response as it is able to inactivate reactive oxygen species (ROS) that produce tissue damage.

Front 343

Fibronogen

Back 343

– Synthesized in the liver.
– Its function is to form a fibrin clot (when activated by thrombin). Fibrinogen is removed in the clotting process and is not seen in serum.

Front 344

What does an increase in ECF lead to?

Back 344

Increase in extracellular fluid results in increased blood volume and arterial pressure.

Normal body response: kidneys excrete excess extracellular fluid and returns the pressure to normal.

Mechanism reverses if reduced blood volume.

Front 345

Renin–Angiotensin system

Back 345

Renin is a hormone that acts as an enzyme. It is released when arterial pressure drops.

Renin converts angiotensinogen to angiotensin I. ACE in the lungs coverts angiotensin I to angiotensin II.

Angiotensin II cause Na+ and water retention in the kidneys and vasocontriction, which increase arterial pressure.

Front 346

Receptors of renin–angiotensin system

Back 346

(P)RR protein receptor
AT1 and AT2 angiotensin receptors
Mas receptor
MR – mineralocorticoid receptor

Front 347

Role of ROS in contraction induced by angiotensin II in vascular smooth muscle cells

Back 347

Red lines show inhibitory effectsand blue lines depict activation.

ROS (reactive oxygen species)
AT1R (angiotensin II receptortype 1)
PLC (phospholipase C)
PIP2 (phosphoinositol biphosphate)
IP3 (inositol 1,4,5 triphosphate)
IP3R (inositol 1,4,5 triphosphatereceptor)
SERCA (sarco/endo–plasmicreticulum Ca2+–ATPase)
GEF (guanine nucleotideexchange factor)
GTP (guanosin triphosphate)
ROCK (Rho–associate kinase)
MLC (myosin light chain).

Front 348

cGMP–PKG

Back 348

Decreases intracellular Ca2+ levelsand promotes the relaxation of smooth muscle

Front 349

Anti–hypertensive

Back 349

Used to antagonize the actions of factors that increase blood pressure.

Used to ‘potentiate’ the actions of factors that decrease blood pressure.

Front 350

Functions of diuretics

Back 350

Diuretics act on your kidneys to help your body eliminate sodium and water, reducing blood volume. The long–term effect is vasodilation and decreased vascular resistance.

Front 351

Beta–adrenergic receptor blockers

Back 351

Reduce the workload on your heart and open your blood vessels, causing your heart to beat slower and with less force.

Front 352

Angiotensin–converting enzyme (ACE) inhibitors

Back 352

Inhibits angiotensin-converting enzyme and prevent the conversion ofangiotensin I to angiotensin II.

Captopril, Enalapril

Front 353

Angiotensin II receptor blockers (ARBs)

Back 353

Losartan, Valsartan

Inhibit actions of angiotensin II by blocking angiotensin type–1 receptors.

Reduce vascular resistance without reducing cardiac output. Renal blood flow is maintained.

These medications are as effective in lowering blood pressure asthe ACE inhibitors.

Front 354

Mechanism of action of beta–adrenergic receptor blockers

Back 354

Lower blood pressure by decreasing cardiac output, inhibiting the release of renin, possibly reducing norepinephrine release from sympathetic neurons, and decreasing central vasomotor activity.

Front 355

Factors affecting neuronal survival and differentiation

Back 355

– Matrix
– Target derived neurotrophic factors (NGF, BDNF, CNTF, GDNF, NT–3)
– Contact (neighbours)
– Developmental window
– Spatial localization

- Activity

Front 356

Irreversible dementia

Back 356

Alzheimer’s
Huntington’s
Parkinson’s
Pick’s
Balo’s
Multi–infarct state
AIDS–related

Front 357

Reversible dementia

Back 357

Chronic drug intoxication
Vitamin deficiencies (B–12 and folate)
Subdural hematoma(s)
Major depression (causing forgetfulness)

Hypothyroidism

Front 358

Mutations leading to Alzheimer disease

Back 358

APP = amyloid precursor protein (Chr 21)

Front 359

Monogenetic causes of Parkinsons´s disease

Back 359

alfa–Synuclein (membrane associated protein)
Parkin (ubiquitinylation)
PINK–1 (mitochondrial kinase)

Front 360

Cause of Huntington´s disease

Back 360

Excessive sequence of CAG repeats in the IT15 gene on arm 4p (mutanthuntingtin)


GABA is low inbasal ganglia

Front 361

Mechanisms involved in Huntington chorea

Back 361

1. Excitotoxicity

2. Oxidative stress

3. Impaired energy metabolism

4. Apoptosis

Front 362

Cause of Friedreich’s ataxia

Back 362

Chromosome 9, frataxin gene is deficient in the 1st intron.

GAA repeat expansion from ~15 to >100 cause gene silencing

Front 363

Normal pH value of the blood plasma

Back 363

7.35 – 7.45

Below 7.35 = acidosis

Above 7.45 = alkalosis

Front 364

pH range in blood plasma compatible with life

Back 364

7.0–7.9

Front 365

The acid–base equilibrium

Back 365

Acid production:
– CO2 (volatile acid)
– Lactic acid
– Ketone bodies
– Other organic acids (from food)

Acid excretion/removal:
– Respiration/lungs (CO2)
– Acid excretion in kidneys
– Metabolism: in cori cycle or as fuels (temporarily)

Base production:
– Amino acid degradation (in balance)
– 2 Glutamine + 3O2 + 6H20 ––> Glucose + 4HCO3– + 4NH4+ (within kidneys)

Base excretion:
– HCO3 – + NH4+ ––> urea (excreted in urine)

*In acidosis increases

* In alkalosis decreases

– HCO3– ––> neutralizes acids in blood
– NH4+ ––> excreted in the kidney

Front 366

The source of CO2

Back 366

Fuel degradation (oxidative decarboxylation of alfa–ketoacids):
– Pyruvate dehydrogenase complex
– Isocitrate dehydrogenase dehydrogenase
– alfa–ketoglutarate dehydrogenase complex
– Degradation of certain amino acids

Spontaneous decarboxylation of beta–keto acids:
– Pentose phosphate pathway
– Acetone formation
– Porphyrin synthesis

Front 367

The fate of CO2

Back 367

Carbonic anhydrase

Carboxylation reactions (not blood CO2 but uses mitochondrial CO2):
– Pyruvate carboxylase
– CPS
– ACC
– Propionyl–CoA carboxylase

Front 368

The control of CO2/HCO3– equilibrium

Back 368

Respiratory control: the chemoreceptor cells

Excretion and reabsorption of bicarbonate in the kidney.

Front 369

The source and fate of lactate

Back 369

Source:
– Anaerobic conditions: (absent mitochondria (e.g RBC) or hypoxia). Glycolysis produces pyruvate and pyruvate is converted to lactate by lactate dehydrogenase.

– Aerobic conditions: in the presence of PFK1–F isozyme, glycolysis is „faster” than pyruvate uptake of mitochondria.

Fate:

- Gluconeogenesis in liver (cori cycle) in hunger

- Energy production in red muscle fibers and in liver in well-fed state

Front 370

Cause of lactic acidosis

Back 370

1. Overproduction of lactate

- intense muscle work

- Oxygen supply problems (anemia etc.)

2. Decreased lactate removal
– Liver insufficiency (alcohol; drug, certain enzyme defects)
– Fructose ingestion ––> pyruvate overproduction

3. Decreased activity of pyruvate dehydrogenase (15–30 % activity)

- Thiamine deficiency and acetyl-coe accumulation

4. Decreased activity of pyruvate carboxylase

Front 371

Examples of free radicals

Back 371

Hydrogen atom
Superoxide
Hydroxyl
Peroxyl, alkoxyl
Oxides of nitrogen

Front 372

Enzymes that generate the superoxide radical

Back 372

Peroxidases
NO synthase
Xhantihine oxidase

Front 373

Definition of inflammation

Back 373

The complex biological response of vascular tissues to harmfulstimuli, such as pathogens, damaged cells, or irritants.

Front 374

5 signs of inflammation

Back 374

Heat
Redness
Swelling
Pain
Loss of function

Front 375

Mechanism of inflammation

Back 375

1. Vasodilation
2. Exudation – edema
3. Emigration of cells
4. Chemotaxis
5. Phagocytosis

Front 376

Comparison between acute and chronic inflammation

Back 376

Front 377

Systemic inflammatory response syndrome (SIRS)

Back 377

At least 2 symptoms:
– Temperature > 38 or < 36 degrees
– Heart frequency > 90
– Respiratory ratio > 20 or PaCO2 < 32 torr (< 4,3 kPa)
– Number of leukocytes > 12 000 cells/mm^3 or <4000 cell/mm^3 or 10% immature (band) cells

Front 378

Sepsis definition

Back 378

SIRS in response to documented infection.

Front 379

Septic shock

Back 379

– Systemic vasodilation and hyptotension
– Tachycardia
– Blood vessel/endothel damage and edema; hypovolemia
– Insufficient blood flow to organs
– Intravascular coagulation
– Abnormal blood gases and acidosis
– Respiratory changes and multiple organ failure

Front 380

Infammatory pathway

Back 380

Pathogen ––> pathogen associated molecular patterns (PAMP) ––> pattern recognition receptor (PRR) ––> response

Front 381

Activation of pancreatic protein and lipid digestion enzymes

Back 381

Front 382

Digestion and absorption of proteins

Back 382

Front 383

Digestion and absorption of carbohydrates

Back 383

Front 384

Digestion and absorption of lipids

Back 384

Front 385

What are the results of degradation of ethanol?

Back 385

1. Acetaldehyde formation

2. Increase ROS formation

3. Increase NADH:NAD+ ratio

Front 386

Where is selenium present?

Back 386

Selenocysteine is present in:

- Glutathione peroxidase: 2GSH+ H2O2 → GSSG + 2H2O

- Deiodinase: T4 --> T3

- Thioredoxin reductase

Front 387

Iron absorption

Back 387

- Iron is kept soluble and in ferrous state by gastric acid.

- Absorbed mainly in duodenum.

- Quantity absorbed regulated by enterocyte.

- Ascorbic acid (vitamin C) enhances absorption of non-animal sources of iron.

- Fe2+ better absorbed than Fe3+.

- DMT-1 = divalent metal transporter 1

Front 388

What is the function of hephaestin?

Back 388

Converts Fe2+ to Fe3+ before the iron enter the circulation.

Front 389

What is the function of ferritin?

Back 389

Iron-storage protein

Front 390

Iron regulation

Back 390

Iron regulates the synthesis of its _own keytransport and storage proteins.

- Iron responsive elements (IREs)

- Iron responsive element binding proteins (IRPs)

Front 391

Hepcidine regulation by iron

Back 391

Hepcidine is synthesized by hepatocytes in the liver.

- Production stimulated with increased pasm iron levels and tissue stores.

- Downregulated in hypoxia, anemia, oxidative stress and ineffective erythropoiesis.

- Negative feedback - hepcidin decreases release of ironinto plasma (from macrophages and enterocytes).

- It binds ferroportin, complex internalised and degraded.

Front 392

Different stages of iron deficiency and anemia

Back 392

Front 393

Toxicity of acetaldehyde

Back 393

- Deactivation of proteins

- Increased collagen production (fibrosis)

- Inhibited DNA repair

- Impaired mitochondrial electron transport chain

Front 394

What type of enzyme activity produces the neurotransmitters dopamine,serotonin and GABA?

Back 394

Decarboxylase

Front 395

Excitation and recovery in the rods (vision)

Back 395

Front 396

Molecular events of olfaction

Back 396

Front 397

Transduction mechanism for taste (sweet)

Back 397

Front 398

List types of sensing that are mediated by 7TMreceptors.

Back 398

7TM receptors = 7-Transmembrane receptors, also known as G-protein-coupled receptors, or GPCRs.

Vision, olfaction, taste: bitter, umami, sweet

Front 399

List the proteins involved in mediating sweet taste (upto generation of action potential).

Back 399

Gustducin (G protein), adenylate cyclase, PKA, K+-channel

Front 400

List the proteins involved in regeneration of rhodopsin.

Back 400

Rhodopsin kinase, recoverin, arrestin

Front 401

Function of voltage sensitive K+ channels

Back 401

Regulates resting potential

Affects excitability of electrically active cells

Front 402

GLP-1

Back 402

Glucagon-like peptide-1

GLP-1 acts on pancreatic α-cells to inhibit glucagonsecretion and thereby reducehepatic glucose production.

Front 403

Local and systemic effects of cytokines produced by activated macrophages

Back 403

Front 404

Definition of apoptosis

Back 404

Programmed cell death (PCD).

Physiological process by which unwanted or useless cellsare eliminated during development and other biologicalprocesses, and ATP level remains close to normal level.

For normal development, maintenance ofcellular homeostasis.

Front 405

Definition of necrosis

Back 405

Cell death is the pathological process which occurs whencells are exposed to a serious physical or chemical insult,and ATP level collapse

Front 406

Phases of apoptosis (3)

Back 406

1. Initiation

2. Effectorphase

3. Degradation phase

Front 407

What can defect of apoptosis cause?

Back 407

- Autoimmune-disorders

- Cancer

- AIDS

Front 408

Phases of cell cycle

Back 408

Front 409

Proto-oncogne

Back 409

Encodes a normal (wild type) protein involved in:

- Promoting cell proliferation

- Inhibiting cell death (apoptosis)

Upon a gain-of-function (single allele) mutation become oncogens.

Front 410

Oncogene

Back 410

A dominant rare mutant allele of a proto-oncogene.

Results in gain-of-function phenotype

- Constitutive activation of celldivision

- Constitutive inactivation ofapoptosis

Front 411

Tumor supressor gene

Back 411

Encodes a normal (wild type) protein involved in:

- Inhibition of cell proliferation

- Promotion of apoptosis

- DNA repair

Recessive, loss-of-function mutations (in both alleles): the cell can not

- Suppress cell division

- Carry out apoptosis

- Repair damaged DNA

Front 412

Cancer development

Back 412

- Accumulation of genetic changes

- Activation of oncogenes

- Inactivation of tumor suppressor genes

- Five or six independent mutational events

Front 413

Classes of protooncogens

Back 413

1. Growth factors: FGF, PDGF

2. Growth factor receptors: EGF receptor

3. Signal transducing proteins:

- Ras (most commonly mutated oncogene)

- Akt (promotes cell survival)

- Abl and Src (non receptor tyrosine kinases)

4. Nuclear transcription proteins: - myc (production of proteins that allow cellsto advance through the cell cycle)

- NFkB (promotes cell survival)

5. Cell cycle regulators

- CyclinD

- CDK4

6. Antiapoptotic proteins: Bcl-2, Bcl-XL

Front 414

Classes of tumor suppressor genes

Back 414

1. Cell surface molecules: TGF-beta receptor (stimulates production of CDL inhibitors)

2. Regulators of signal transduction: NF-1, APC

3. Nuclear transcription proteins

- RB (inhibits entrance into S phase)

- p53 ( regulates cell cycle + apoptosis - mots common molecular alternation in cancer)

4. Cell cycle regulators: CDK inhibitors (p16, p21, p17)

5. Proapoptopic protiens: Ba, Bad, Bak

Front 415

Beta-adrenergic pathway (GPCR signaling)

Back 415

Front 416

Regulation of:

PFK-1

FBpase-1

Glycogen phosphorylase

Pyruvate dehydrogenase complex

Carbamoyl phosphate synthase

Glycogen synthase

Isocitrate dehydrogenase

Citrate synthase

Alfa-ketoglutarate dehydrogenase

Acetyl-CoA carbocylase (ACC)

HMG-coA reductase

Pyruvate kinase (muscle + liver)

Back 416

Front 417

What does HbA1c consist of? What does its concentration in blood refer to?

Back 417

HbA1c is glycated hemoglobin. Consist of glucose and hemoglobin.

It's concentration is used to identify the long term (3-month) average plasma glucose concentration.

Front 418

How galactose enter glycolysis?

Back 418

Galactose --> Galactose-1-p --> UDP-galactose --> UDP-glucose --> Glucose-1-phosphate --> Glucose-6-phosphate

Galactokinase --> Gal-1-P

UDP-glucose: Galactose-1-phosphate uridyltransferase --> UDP-Gal

UDP-glucose 4-epimerase --> UDP-Glc

UDP-glucose: Galactose-1-phosphate uridyltransferase --> Gal-1-p

Phosphoglucomutase --> Gal-1-p

Front 419

How fructose enter glycolysis?

Back 419

Fructose --> hexokinase

Enters at fructose-6-phosphate in step 3

Front 420

How mannose enter glycolysis?

Back 420

Mannose --> mannose-6-P

(Hexokinase)

Mannose-6-p --> fructose-6-p

(Phosphomannose isomerase)

Front 421

How fructose-1-P enter glycolysis?

Back 421

F-1-P --> glyceraldehyde + dihydroxyacetonephosphate (F-1-p aldolase)

Glyceraldehyde --> glyceraldehyde-3-p

(Triose kinase)

Dihydroxyacetone phosphate --> glyceraldehyde -3-p-

(triose phosphate isomerase)

Enters at 6 stage of glycolysis

Front 422

Which nuclear receptor enhances glucose uptake?

Back 422

PPAR gamma