Biochemistry

Front 1

B complex

1, 2, 3...

Back 1

B1 - thiamine (TPP)
B2 - riboflavin (FAD, FMN)
B3 - niacin (NAD)
B5 - pantothenate (CoA)
B6 - pyridoxine (pyridoxal phosphate)

Biotin (B7)
Folate (B9)

Front 2

TPP is a cofactor for what enzymes?

Back 2

PDH, alpha-ketoglutarate dehydrogenase, transketolase

Front 3

B2 deficiency

Back 3

riboflavin deficiency

stomatitis, chelosis, and corneal neovascularization

Front 4

Causes of pellagra

Back 4

Niacin deficiency: 3 D's and beefy glossitis.

-Hartnup disease (diminished tryptophan absorption)
-Malignant carcinoid syndrome
-INH (it decreases B6)

Front 5

B5 deficiency

Back 5

pantothenate deficiency

dermatitis, enteritis, alopecia, adrenal insufficiency

Front 6

B6 deficiency


Where is B6 used?

Back 6

pyridoxine deficiency

Convulsions, hyperirritability, peripheral neuropathy

Converted to PP, used in transamination, decarboxylation, and heme synthesis (and glycogen phosphorylase, ammonia shuttling)

Front 7

Causes of B12 deficiency

Back 7

-Malaborption: sprue, diphyllobothrium latum

-Lack of intrinsic factor

- Absence of terminal ileum (Crohn's and surgery)


Remember B12 is synthesized only by microorganisms.

Front 8

2 essential reactions that B12 takes part in.

Back 8

1. Homocysteine-->Methionine via methionine synthase

2. Methylmalonyl-CoA-->Succinyl-CoA

Front 9

Why is folate needed for synthesis of nitrogenous bases?

Back 9

Thymidylate synthase relies on folate and dihydrofolate reductase for function.

Folate (specifically, DHF & THF) is very good at methyl transfers.

Front 10

Methotrexate and aminopterin: how do they work?

Back 10

They are analogs of dihydrofolate which inhibit dihydrofolate reductase.

This messes with thymidylate synthase, particularly.

Front 11

Biotin deficiency

What is it a cofactor in?

Back 11

Dermatitis, enteritis

Can be precipitated by eating lots of raw eggs (avidin in egg whites binds biotin)

Cofactor in: pyruvate carboxylase, fatty acid synthesis, and fatty acid breakdown

Front 12

Three functions of ascorbate

Back 12

Vitamin C

1. Hydroxylation of lysine and proline residues for collagen synthesis.

2. Facilitates iron absorption (keeps Fe+2)

3. Necessary cofactor for dopamine hydroxylase

Front 13

Deficiency of vitamin E

Back 13

Fragile RBCs, ataxia (affecting dorsal columns, spinocerebellar tracts)

Front 14

Zinc deficiency

Back 14

delayed wound healing, hypogonadism, decreased adult hair, predispose to alcoholic cirrhosis

Front 15

Kwashiorkor versus Marasmus

Back 15

Protein malnutrition vs. Calorie malnutrition

Kwashiorkor: skin lesions, edema, fatty change, swollen belly.

Marasmus: wasting, loss of SC fat, and variable edema.

Front 16

Histone "octamer" components

Back 16

2 x (H2a, H2b, H3, H4)

H1 is not in the nucleosome core; it's not part of the octamer. It helps arrange nucleosomes into 30 nm fibers.

Front 17

What are the most represented AAs in histones?

Back 17

Arginine and Lysine

1/4 of all AAs are R/K.

Front 18

Purines?

Back 18

A
G

Front 19

Pyrimidines?

Back 19

T
C
U

Front 20

Cytosine deamination

Back 20

Makes a uracil, which pairs with A rather than G.

This can produce mutations.

Front 21

What amino acids are necessary for purine synthesis?

Back 21

Glycine
Aspartate
Glutamine

Front 22

Exceptions to the universality of the genetic code?

4 of 'em

Back 22

Mitochondria
Archaebacteria
Mycoplasma
some Yeasts

Front 23

How many codons encode methionine?

Back 23

only one

Front 24

Exceptions to the "nonoverlapping"ality genetic code

Back 24

some viruses

Front 25

DNA pol III

Back 25

the main eukaryotic DNA polymerase

5' to 3' synthesis
3' to 5' proofreading/exonuclease

Front 26

DNA pol I

Back 26

degrades RNA primers with a 5'-->3' exonuclease activity

Front 27

p53 (chromosome 17p)

Back 27

Senses DNA damage, especially double strand breaks, and it promotes either apoptosis or DNA repair

Front 28

Nucleotide excision repair

+ disease

Back 28

Several bases are removed by endonucleases... DNA pol and ligase fill the gap. Particularly important for removal of pyridine dimers made by UV light.

Xeroderma

Front 29

Base excision repair

Back 29

glycosylases recognize and remove damaged bases... important for repair after cytosine deamination.

Front 30

Mismatch repair

+disease

Back 30

corrects errors not corrected by proofreading

HNPCC (aka Lynch syndrome): hMSH2, hMLH1 are damaged. These guys are homologues of mutS and mutL MMR genes.

Front 31

NHEJ

Back 31

brings together two ends of DNA fragments, without requirement for homology.

Relies on Ku proteins that bind the free DNA ends

Front 32

Massive, Rampant, Tiny

referring to RNA types, what does this mean?

Back 32

mRNA is the largest
rRNA is the most abundant
tRNA is the smallest

Front 33

alpha-amanitin

Back 33

found in death-cap mushrooms, inhibits RNA pol II, preventing transcription

Front 34

How many RNA pols do prokaryotes have?

Back 34

Just one multisubunit complex that does just about everything

Front 35

Start codon (s)

Back 35

AUG, codes for methionine or f-Met

Front 36

Stop codons

Back 36

UAA, UAG, UGA

Front 37

Features of a promoter

Back 37

AT rich sequence with TATA and CAAT boxes, just upstream from gene locus

Front 38

Where does RNA processing occur?

Back 38

In the nucleus.

Front 39

RNA processing steps

Back 39

1. Capping: 5' end gets 7methylG
2. PolyA tail: 3' end
3. Splicing of introns

Initial transcript is called hnRNA.
Capped and tailed transcript is called mRNA.

Front 40

tRNA structure: 4 different arms

Back 40

- Acceptor stem: 5' terminal phosphate, 3' CCA tail (holds AA)

- D arm - lots of dihydrouricil

- T arm - has the TYC sequence, needed for binding tRNA to ribosomes,

- Anticodon arm - interacts with mRNA

Front 41

How many aminoacyl tRNA synthetases are there?

Back 41

~20; 1 per AA

Front 42

How are damaged proteins tagged for degradation?

Back 42

they get ubiquitinated and brought to the proteosome

Front 43

What posttranslational modifications happen in the RER?

Back 43

N-linked glycosylation

Front 44

Functions of Golgi apparatus: 7 at least

Back 44

1. Distribution center for ER --> membranes, lysosomes, secretory vesicles

2. Modify N-oligosaccharides on asparagine

3. o-linked glycosylation

4. Adds mannose-6-phosphate to lysosomal proteins to target them to lysosome

5. Proteoglycan assembly

6. Sulfation of sugars in proteoglycans and of tyrosine residues

7. Glycosylation of prepro alpha chain lysine residues to form pro-collagen triple helix

Front 45

COPI, COP II

Back 45

COPI: retrograde, golgi-->ER

COPII: anterograde, ER-->cis Golgi

Front 46

Microtubule: components?

Back 46

Alpha and Beta tubulin dimers, each dimer has 2 GTP bound

Front 47

Chediak-Higashi

genetics
features

Back 47

Autosomal recessive mutation of LYST

LYST defect affects synthesis/maintenance of storage vesicles and lysosomes. You will see huge lysosomes on peripheral blood smears.

Patients have albinism, immune deficiency, among other defects.

Front 48

Cilia

Structure
Motor

Back 48

9+2 arrangement of microtubules

dynein is the motor

Front 49

Dynein vs. kinesin

which is anterograde/retrograde?

Back 49

dynein - retrograde
kinesin - anterograde

Front 50

What are the major components of the plasma membrane?

Back 50

cholesterol, phospholipids (each 50%)

others: protein, sphingolipids, glycolipids

Front 51

What is LCAT?

Back 51

lethicin-cholesterol acyltransferase

used in the esterification of cholesterol

Front 52

Inhibitors of the 3Na/2K-ATPase

at least 2

Back 52

Ouabain
Cardiac glycosides

Front 53

Collagen types

I
II
III
IV

Back 53

I: bone, skin, tendon, dentin, cornea, late wound repair...

II: cartilage, vitreous body, nucleus pulposus

III: (reticulin), skin, vessels, uterus, granulation tissue

IV: basement membranes

Front 54

Osteogenesis imperfecta

Back 54

Abnormal type I collagen

Most common form is AD

Multiple fractures, blue sclerae, hearing loss (abnormal ossicles), dental imperfections

Front 55

What happens in mitochondria?

Back 55

TCA cycle, Beta oxidation, acetyl-CoA production

Front 56

What happens in cytoplasm?

Back 56

Glycolysis, fatty acid synthesis, HMP shunt, protein synthesis, steroid synthesis

Front 57

What happens in both cytoplasm and mitochondria?

Back 57

Gluconeogenesis, urea cycle, heme synthesis

Front 58

ATP yield using malate shuttle

using G3P shuttle

Back 58

38

36

Front 59

TPP carries what?

Back 59

aldehydes

Front 60

NADPH is used in 3 different processes requiring reducing equivalents...

Back 60

1. Anabolism

2. Respiratory burst

3. P-450

Front 61

Catalase: generates H2O and O2 from H2O2... what does it use?

How is it replenished?

Back 61

It uses glutathione, which is replenished by glutathione reductase (which uses NADPH, which is regenerated by G6PD)

Front 62

G6PD deficiency makes you susceptible to oxidative stress how?

Back 62

It impairs the regeneration of NADPH and thus the regeneration of reduced glutathione.

Front 63

Glucokinase: liver or muscle?

Back 63

Liver
Low affinity, high capacity
Unregulated

Front 64

What enzyme of glycolysis does alanine inhibit?

Back 64

pyruvate kinase (PEP-->Pyruvate)

note: alanine goes to pyruvate which can be used in gluconeogenesis. So it makes sense to not do glycolysis when you can get pyruvate off the bat from alanine.

Front 65

What enzyme of glycolysis does citrate inhibit?

Back 65

PFK1

Front 66

PFK2: what is it made of, what does it do, how is it regulated

Back 66

PFK2 consists of fructose bisphosphatase2 (active when phosphorylated) and PFK2 (inactive when phosphorylated)

It makes F2,6BP (a potent activator of PFK1)

PFK2 is activated by phosphoprotein phosphatase in setting of high fructose-6-phosphate

PFK2 is inactivated by PKA in response to glucagon.

Front 67

Glycolytic enzyme deficiency: disease, most common enzymes

Back 67

hemolytic anemia

Pyruvate kinase (95%)
Glucose phosphate isomerase (4%)
Hexokinase, aldolase, etc.

Front 68

What does arsenic do?

Back 68

Inhibits lipoic acid (used in PDH and KDH)

Vomiting
Ricewater stools
Garlic breath

Front 69

PDH cofactors

(incidentally, ketoglutarate dehydrogenase cofactors)

Back 69

B1, B2, B3, B5, lipoate

Front 70

Pyruvate dehydrogenase deficiency

What is it?
What does it cause?
How do you treat it?

Back 70

Causes a backup of pyruvate and alanine, leading to lactic acidosis.

Associated with neurologic defects.

Treatment: increased intake of (lysine and leucine) ketogenic nutrients

Front 71

Glucose alanine cycle

Back 71

Muscles use amino acids as fuel. Nitro groups are transferred to pyruvate to form alanine, which is transported to the liver and converted into glucose via pyruvate.

Front 72

What happens to lactate in the cori cycle?

Back 72

Liver and heart use lactate dehydrogenase to make pyruvate.

Liver makes glucose from that.
Heart shuttles pyruvate into the TCA cycle.

Front 73

Can I Keep Selling Sex For Money Officer?

Back 73

Citrate--> Isocitrate--> ketoglutarate--> succinylCoA--> succinate--> Fumarate--> Malate--> Oxaloacetate

Front 74

Electron transport inhibitors

Back 74

Rotenone, CN, antimycin A, CO

Front 75

ATPase inhibitors

Back 75

Oligomycin

Front 76

Uncouplers

Back 76

2,4 DNP, Aspirin, UCP (thermogenin)

Front 77

How many H+ are pumped out at each complex in the ET chain?

Back 77

4... so NADH pumps out 12

4 H+/ATP: Complex V (ATPase) has 4 subunits

Front 78

The 4 irreversible enzymes of gluconeogenesis

Back 78

1. Pyruvate carboxylase: pyruvate-->oxaloacetate

2. PEP carboxykinase: oxaloacetate-->PEP

3. Fructose-1,6-bisphosphatase: makes fructose-6-p

4. Glucose-6-phosphatase (In ER): makes glucose

Front 79

Deficiency of any gluconeogenic enzyme causes what?

Back 79

Hypoglycemia

Front 80

Where are the enzymes of gluconeogenesis found?

Back 80

Liver, Kidney, intestinal epithelium

Front 81

Oxidative reactions of HMP shunt: what do they produce?

What's the key enzyme?

Back 81

CO2, NADPH (2 per molecule of G6P)

G6PD is the key enzyme

Front 82

Nonoxidative reactions of HMP shunt: what do they produce?

Key enzymes?

Back 82

Ribose 5 phosphate, G3P, F6P

Transketolases (requires TPP)

Front 83

A person with G6PD deficiency is susceptible to what things?

Back 83

Fava beans
Primaquine
Sulfonamides
Dapsone
Anti-TB drugs

Front 84

G6PD deficiency

-Inheritance, epidemiology
-Findings on blood smear

Back 84

X linked recessive
More prevalent in blacks

Heinz bodies - hemoglobin precipitates in RBC
Bite cells

Front 85

Glutathione: what does it do for hemoglobin?

Back 85

It keeps cysteine residues of hemoglobin in a reduced state!

Front 86

2 disorders of fructose metabolism

Back 86

1. Fructose intolerance: AR, deficiency of Aldolase B, leading to accumulation of fructose 1 phosphate and a decrease in available phosphate, shutting off gluconeogenesis and glycogenolysis.
Hypoglycemia, jaundice, cirrhosis, vomiting

2. Essential fructosuria: defect in fructokinase and is benign and asymptomatic, but there's lots of fructose in the blood and urine.
It's benign because fructose can be turned into fructose 6-phosphate by hexokinase (so you don't really need fructokinase)

Front 87

2 disorders of galactose metabolism

Back 87

1. Classic galactosemia: absence of galactose-1-phosphate uridyltransferase; AR; causes buildup of galactose and galactitol.
TRT: avoid galactose and lactose (glucose + galactose)

2. Galactokinase deficiency: galactosemia and and galactosuria, and galactitol... basically same as above but the first enzyme there.

Front 88

Lactose --> ?

Back 88

glucose and galactose via LACTASE

Front 89

Sucrose --> ?

Back 89

glucose and fructose via SUCRASE

Front 90

What amino acids are essential?

Back 90

LK (ketogenic) IFW (both) MVRTH (glucogenic)

Front 91

Signs of ammonia intoxication

Back 91

Tremor, slurring of speech, somnolence, vomiting, cerebral edema, blurring of vision

Front 92

What does ALT catalyze?

Back 92

alanine + alpha-ketoglutarate --> pyruvate + glutamate

This is part of alanine cycle

Front 93

What cofactor do the aminotransferases use?

Back 93

B6

Front 94

Causes of ammonia intoxication

treatments for them

Back 94

1. Ornithine transcarbamoylase deficiency: supplement with benzoate and phenylacetate

2. Arginosuccinase deficiency: supplement with arginine

3. Can be acquired (liver disease)

Front 95

What is the purpose of the urea cycle?

Back 95

It functions to get rid of excess nitrogenous waste NH4.

Thus, with some of these disorders, you can treat them by just getting rid of nitrogenous waste in tricky ways (e.g. pissing out arginosuccinate, pissing out glycine & glutamine)

Front 96

PKU

Back 96

AR; defect in phenylalanine hydroxylase or tetrahydrobiopterin; tyrosine becomes essential, tryptophan builds up.

Findings: MR, growth retardation, fair skin, musty body odor, eczema

Phenylketones build up in urine

Front 97

Alkaptonuria

Back 97

AR; deficiency of homogentisic acid oxidase in degradative pathway of tyrosine.

Urine turns black on standing (alkapton bodies).

Front 98

Albinism: potential defects.

Back 98

1. Tyrosinase
2. Defective tyrosine transporters
3. Lack of NC cell migration

Front 99

Homocystinura: 3 defects

Features

Back 99

All are AR.

1. Cystathionine synthase deficiency
2. Decreased affinity of cystathionine synthase for B6
3. Methionine synthase deficiency

Cysteine becomes essential.

Features: MR, osteoporosis, tall stature, kyphosis, lens subluxation, and atherosclerosis

Front 100

Cystinura

Back 100

Defect in COLA (cysteine, ornithine, lysine, arginine) reuptake transporter

Predispose to cysteine stones.

Treat by alkalinizing the urine.

Front 101

Maple syrup urine disease (branched chain ketoacidura)

Back 101

AR defect in alpha-ketoacid dehydrogenase. I, V, L build up quite a bit (they're branched).

Features: MR, severe CNS defects, death

Treatment: low I, V, L diet

Front 102

Xanthine oxidase

Back 102

Contains iron and molybdenum.

Allopurinol inhibits XO by interfering with molybdenum.

Front 103

ADA deficiency: the defect.

Back 103

Can cause SCID.

Excess ATP and dATP imbalances nucleotide pool by feedback inhibiting ribonucleotide reductase (makes DNAs from RNAs)

Front 104

Lesch-Nyhan syndrome

-Genetics
-Defect
-Findings

Back 104

X linked recessive

Absence of HGPRTase, which converts hypoxanthine to inosine monophosphate and guanine to guonosine monophosphate (saving the purines from being catabolized). Increased denovo synthesis of purines, increased uric acid production.

Findings: retardation, self mutilation, aggression, gout, choreoathetosis, spasticity, kidney stones.

Front 105

What are the ketone bodies?

Back 105

acetoacetate, hydroxybutyrate

Front 106

Where is
- GLUT 1
- GLUT 2
- GLUT 4
- GLUT 5

Back 106

1 - RBCs, brain
2 - Beta cells, liver, kidney
4 - muscle, fat (increased by endurance training)
5 - small intestine, functions as a fructose transporter

Front 107

Glycogen synthase/ phosphorylase. Which one is active when phosphorylated?

Back 107

Glycogen PHOSphorylase is active when phosphorylated (activated by hormones and calcium)

Front 108

What does glycogenolysis produce?

Back 108

Glucose 1 phosphate, which is turned into glucose 6 phosphate by phosphoglucomutase.

Front 109

What's going on with alpha-1-4 glucosidase?

Back 109

It's a lysosomal enzyme that degrades a small amount of glycogen... and it's obviously a place for pathology and more examinable material (!!)

Front 110

Type I glycogen storage disease

Back 110

Von Gierke's disease

Glucose 6 phosphatase, G-6-P transporter (can't release glucose from liver)

Findings: severe fasting hypoglycemia, increased liver glycogen, increased blood lactate, hepatomegaly, convulsions

Front 111

Type II glycogen storage disease

Back 111

Pompe's disease

Lysosomal alpha-1,4-glucosidase (acid maltase)

Cardiomegaly and systemic findings leading to early death

Front 112

Type III glycogen storage disease

Back 112

Cori's disease

Debranching enzyme (1,6 glucosidase)

Milder form of type I with normal blood lactate

Front 113

Type IV glycogen storage disease

Back 113

Andersen disease

Branching enzyme defect, leads to very long outer branches

Cirrhosis and death by age 2

Front 114

Type V glycogen storage disease

Back 114

McArdle's disease

Defect in skeletal muscle glycogen phosphorylase

Painful muscle cramps, myoglobinuria

Front 115

What are the two X linked lysosomal storage diseases?

Back 115

1. Fabry's disease

2. Hunter's syndrome

All others are AR

Front 116

Fabry's

Back 116

Neuropathy, angiokeratomas, CV/renal disease

galactosidase A

Ceramide trihexoside

Front 117

Gaucher's

Back 117

Hepatosplenomegaly, bone crises, Gaucher's cells (tissue paper)

glucocerebrosidase

glucocerebroside

Front 118

Nieman-Pick

Back 118

Neurodegeneration, hepatosplenomegaly, cherry red spot

Sphingomyelinase

Sphingomyelin

Front 119

Tay-Sachs

Back 119

Neurodegeneration, developmental delay, cherry red spot, lysozymes with onion skin

Hexosaminidase A

GM2 ganglioside

Front 120

Krabbe's

Back 120

neuropathy, developmental delay, optic atrophy, globoid cells

Galactosyl ceramidase

Galactocerebroside

Front 121

Metachromatic leukodystrophy

Back 121

Demyelination with ataxia, dementia

Arylsulfatase A

Cerebroside sulfate

Front 122

Hurler's syndrome

Back 122

Delay, gargoylism, airway obstruction, corneal clouding, hepatosplenomegaly

alpha-L-iduronidase

Heparan sulfate, dermatan sulfate

Front 123

Hunter's syndrome

Back 123

Mild hurler's plus aggressive behavior, no corneal clouding

Iduronate sulfatase

Heparan sulfate, dermatan sulfate