Biochemistry Block 3

Front 1

Essential Amino Acids

Back 1

LIL TV PM HA

Leucine
Isoleucine
Lysine

Threonine/Tryptophan
Valine

Phenylalanine
Methionine

Histidine
Arginine

Front 2

PLP

Back 2

Pyridoxal Phosphate

Derived from Pyridoxine, which is Vitamin B6

Front 3

Most abundant AA in the serum?

Back 3

Glutamine!

Front 4

CC

Homocystinuria

Back 4

Abnormal Homocysteine Metabolism

Result: Increased levels of Homocysteine or Homocystine

Neural Tube Defects AND Vascular Disease

Front 5

CC

Cystinuria

Back 5

Defect in transport protein that permits resorption of cystine in renal tubular cells (PLASMA MEMBRANE)

Result: Increased Cystine and formation of cystine stones (one type of kidney stones)

Front 6

CC

Cystinosis

Back 6

Defect in transport protein that removes cystine from LYSOSOMES

Result: Accumulation of cystine in lysosomes and formation of crystals

Front 7

CC

Phenylketonuria (PKU)

Back 7

Deficiency of Phenylalanine Hydroxylase (PAH), Dihydropteridine Reductase, or Enzymes in biosynthetic pathway for BH4

Result: Accumulation of Phenylalanine forces it to be metabolized by transamination, giving rise to Phenylketones (Phenylpyruvate, Phenylacetate, and Phenyllactate)

Phenyketones cause serious neurological diseases

Front 8

Where are phospholipids synthesized?

Back 8

Phosphatidylglycerol and Cardiolipin (Diphosphatidylglycerol) = Mitochondria

All Other Types = ER

Front 9

Where is Cardiolipin (Diphosphatidylglycerol) Localized?

Back 9

IMM - Required for normal FX

Front 10

Where is Phosphatidylglycerol Localized?

Back 10

Component of Extracellular Surfactant of the Lung

Front 11

What is Phosphatidylserine derived from?

Back 11

Phosphatidylethanolamine OR Phosphatidylcholine via the addition of Serine and Loss of Ethanolamine/Choline, respectively!

Phosphatidylserine can be reconverted ONLY to Phosphatidylethanolamine via loss of CO2!

Front 12

Platelet-Activating Factor (PAF)

Back 12

An Ether Lipid

R2 = CH3

Vascular regulator, released from phagocytic blood cells.

Induces blood platelet aggregation, vessel dilation, edema

Part of the ALLERGIC RESPONSE

Front 13

PhosphatidAl Choline

Back 13

A Vinyl Ether (Plasmalogen)

Found in Heart Muscle AND Myelin Membrane

Synthesized in membranes of PEROXISOMES

Antioxidant Properties

Front 14

CC

Zellweger's Syndrome

Back 14

Characterized by defects in PEROXISOME biogenesis

Result: REDUCED PLASMALOGEN (Antioxidant) BIOSYNTHESIS

Front 15

CC

What are reduced levels of Cariolipin (Diphosphatidylglycerol) associated with?

Back 15

Age-related mitochondrial dysfunction!

Front 16

CC

Barth Syndrome

Back 16

Male Inherited (X-Linked) Disorder

Caused by imbalance in fatty composition and level of Cardiolipin; Increased levels of Monolysocardiolipin

Result: Cardiac and Skeletal Myopathy characterized by susceptibility to infection

Front 17

CC

Anti-Cardiolipin Antibodies

Back 17

2.5% of Population has them

Presence does NOT NECESSARILY mean disease

Can be one of the causes of RECURRENT MISCARRIAGES

Front 18

Why does Phospholipase A2 in Snake Venom result in Hemolysis?

Back 18

Arachidonic Acid AND Lyso-Phospholipids released from phospholipid membrane disproportionately! Breaks down erythrocyte membrane!

Front 19

Nomenclature of Prostaglandins:

Back 19

PGXn

X = Ring Structure/Substituents
-D= Carbonyl C BELOW
-E= Carbonyl C ABOVE
-F= Both Hydroxyl

n=Number of Double Bonds OUTSIDE of Ring

Front 20

Function of Glutathione + LTA4 Derived Leukotrienes (LTC4, LTD4, LTE4)

Back 20

Vascular Permeability, Leukocyte Proliferation, Bronchoconstriction

Blocking these effects can alleviate complications of Asthma. This is what Singulair does!

Front 21

Nomenclature of Gangliosides

Back 21

GXn

X= M, D, or T for Monosialic/Disialic/Trisialic Acid

n= 5 - # of Neutral Sugars (non-neutral are ones w/ NANA aka Sialic Acid attached)

Front 22

Aspirin Induced Asthma

Back 22

Aspirin, a NSAID, inhibits Cyclooxygenase (COX) but NOT Lipoxygenase

Result: Arachidonic Acid flows to Leukotriene Synthesis, its other possible fate! This worsens asthma!

Front 23

Aspirin Effects

Back 23

Blocks Cyclooxygenase (COX) by donating its acetyl group to it!

Result: Prostaglandin/Thromboxanes synthesis reduced or halted.

Essential for Anti-Platelet Therapy in HEART and VASCULAR DISEASE

Aspirin is single MOST EFFECTIVE therapy for reducing mortality in heart disease above all others!

Front 24

What supplies the BRAIN with Cholesterol?

Back 24

Itself!

Must make its own!

Why? CANNOT import cholesterol made in Liver due to BBB!

Front 25

What are the ISOPRENES (C5 Units) involved in Cholesterol Biosynthesis derived from?

Back 25

Acetate!

Front 26

HMGCOa Synthase Localizations/Functions:

Back 26

Mitochondrial Enzyme = KB Synthesis

Cytosolic Enzyme = Cholesterol Synthesis

Front 27

How many Acetyl-CoAs are required to generate HMGCoA?

Back 27

3!

Front 28

Carbon Units Involved in Cholesterol (C27) Biosynthesis:

Back 28

5,10,15,30 ID Girl Friend Stephanie

C5 = Isopentenyl-PP AND Dimethylallyl-PP

C10 = Geranyl-PP

C15 = Farnesyl-PP

C30 = Squalene

Front 29

Where does most Cholesterol Biosynthesis take place?

Back 29

Liver ENDOPLASMIC RETICULUM

Front 30

Roles of MIXED FUNCTION OXIDASE (Monooxygenase) in final CONVERSION of LANOSTEROL (Squalene --> Squalene Epoxide --> Lanosterol) to CHOLESTEROL: (3)

Back 30

Remove Reduce Migrate

1) Remove 3 -CH3s: C4(2) and C14(1)

2) Reduce Double Bond at C24

3) Migrate Double Bond at C8 to C5

Front 31

Insulin/Glucagon Effects on HMGCOa Reductase (Rate Limiting Step of Cholesterol Biosynthesis)

Back 31

Covalent Modification!

Glucagon - Phosphorylates = Inactivation

Insulin - Dephosphorylates = Activation

Front 32

Lovastatin Effects (Lipitor, Pravachol, Lescol, Mevacor)

Back 32

COMPETITIVE INHIBITORS of HMGCOa Reductase!

Used to manage cholesterol levels.

Also reduce inflammatory response.

Front 33

What two amino acids are Bile Salts/Acids conjugated to?

Back 33

Glycine or Taurine!

Front 34

Primary VS Secondary Bile Acids

Back 34

Primary:
-Cholesterol --> Cholic Acid and Chenodeoxycholic Acid
-FORMED IN LIVER

Secondary:
-Primary Bile Acids --> Deoxycholic and Lithocholic Acid
-FORMED IN INTESTINE BY INTESTINAL BACTERIAL ENZYMES

Front 35

Ursodiol

Back 35

Drug which is a bile acid used to dissolve otherwise uncomplicated small cholesterol stones in patients who cannot have a cholecystectomy

Front 36

Cholestyramine

Back 36

Drug that acts as a bile acid sequestrant - binds bile and PREVENTS REABSORPTION

Front 37

Lipid Composition of Inner/Outer Layers of Biological Membranes:

Back 37

Large head groups appear preferentially on OUTER SURFACE

Outer: PC, S
PhosphatidylCholine, Sphingomyelin

Inner: PS, PE
PhosphatidylSerine, PhosphatidylEthanolamine

Front 38

Endogenous Insulin vs Exogenously Administered Insulin

Back 38

C-Peptide of Proinsulin is ONLY associated with ENDOGENOUS Insulin!

If a hypoglycemic patient has HIGH levels of C-Peptide in their blood, it is due to excess ENDOGENOUS Insulin

Front 39

N-Linked vs O-Linked Glycosylation

Back 39

N-Linked: O-Linked

1) Involves Dolichol Phosphate: Does NOT

2) Attaches to ASPARAGINE CO-TRANSLATIONALLY in ER: Attaches to SERINE OR THREONINE POST-TRANSLATIONALLY in GOLGI

3) Inhibited by Tunicamycin or Bacitracin: Is NOT

Front 40

Warburg Effect:

Back 40

Facilitative glucose transport is INCREASED in Cancer Cells

Front 41

Ouabain

Back 41

Specific Inhibitor of Na, K, ATPase Transporter

Considered a Cardiotonic Steroid which is derived from plants

Binds the Outside ONLY (alpha subunit)!

Front 42

Tamoxifen Drug Action

Back 42

Used to treat hormone-dependent breast cancer

Estradiol analog, inhibits action of Estradiol on gene expression by blocking binding site on Estrogen Receptor.

Front 43

How is cAMP Phosphodiesterase Activated/Inhibited?

Back 43

Activated - Ca2+ Calmodulin Complex

Inhibited - Caffeine and Theophylline

Front 44

G Protein Families:

1) Gs
2) Gi
3) Transducin
4) Gq

Back 44

1) Stimulates Adenylate Cyclase
2) Inhibits Adenylate Cyclase
3) Stimulated cGMP Phosphodiesterase
4) Increases IP3 and Intracellular Calcium

Front 45

Inhibition of Beta-Adrenergic Receptor

Back 45

HORMONE-RECEPTOR COMPLEX (not unbound receptor) is Phosphorylated

Beta-Arrestin then binds phosphorylated rector, diminishing its G-Protein activity.

Front 46

Cholera Toxin

Back 46

Binds cells lining intestine where it stimulates their adenylate cyclase activity, causing unregulated salt and water secretion.

3 Peptides: A1, A2, B in amounts of 1:1:5

B subunits (5 per molecule) - bind Ganglioside GM1 Receptor

Binding causes disulfide bond between A1 and A2 to be split, activating A1.

Active A1 enters cell through pore of B subunits and catalyzes ADP-ribosylation of the alpha-subunit of the G protein.

This blocks GTPase activity of G protein, locking it into active state.

CFTR activated via PKA-mediated phosphorylation of its regulatory subunit

Front 47

Pertussis Toxin

Back 47

ADP-ribosylates the Alpha-Subunit of the Gi G-Protein

This inhibits adenylate cyclase in GTP bound form, or stabilizes if in the GDP bound form.

Front 48

Diptheria Toxin

Back 48

ADP Ribosylates Elongation Factor II (EF-2)

Toxin activated after binding to cell via proteolytic cleavage

Prevents translocation step, stopping protein synthesis

Front 49

Anthrax Toxin

Back 49

One protein of complex is Edema Factor (EF)

EF binds Calmodulin, inhibiting it.

Calmodulin-EF Complex becomes a catalytically active adenylate cyclase

Result: Increase cAMP and inhibition of inflammatory responses involved in host defense

Front 50

Cholesterol vs Cholesterol Ester

Back 50

Cholesterol = Cell Membranes

Cholesterol Ester = Plasma Lipoproteins and Storage in Cells

Front 51

What cells do NOT make Cholesterol?

Back 51

RBCs!

Front 52

Which AAs are bile salts/acids conjugated to in amide linkages?

Back 52

Glycine or Taurine

Front 53

Rate Limiting Step of Bile Synthesis

Back 53

Cholesterol 7alpha-Hydroxylase

Cholic Acid INHIBITS
Cholesterol ACTIVATES

Front 54

Role of Colonic Bacteria in Bile Synthesis

Back 54

Remove 7alpha-OH

Form SECONDARY Bile Acids

Cholic Acid --> DEOXYCHOLIC ACID
Chenodeoxycholic Acid --> LITHOCHOLIC ACID

Front 55

What bile is excreted?

Back 55

Reabsorbed LITHOCHOLIC ACID is SULFATED in the liver and excreted on the next pass (this, is only reabsorbed ONCE)

Front 56

What phospholipid is secreted with Bile?

Back 56

PhosphatidylCHOLINE

Front 57

Another name for Phosphatidylcholine

Back 57

Lecithin

Front 58

Diabetes and LDL

Back 58

Glycated Phosphatidylethanolamine (Covalently Bound Glucose)

Activates Macrophage Uptake

Front 59

Structural Characteristics of Cholesterol Derived Molecules

Back 59

Cholesterol: C27 (Side Chain is 8 C's)

Bile Salts/Acids: Shortened Side Chain w/Carboxyl or Amide Group

Progestagens: C21 w/ ONE Oxygen on Ring

Corticoids: C21 w/ MANY OH's

Androgens: C19

Estrogen: C18 + Aromatic Ring

Front 60

Conjugation of Cholesterol in Cholesterol Catabolism

Back 60

Conjugation at C3-OH with Glucuronic Acid OR Sulfate

Front 61

Proteoglycans

Back 61

Protein Core + Glycosaminoglycans (GAGs) Linked by Xylose-Galactose-Galactose Link Trisaccharide)

Form Gel of ECM

Effective Lubricant

Highly Negatively Charged and Hydrated - Bind EC Proteins via ELECTROSTATIC INTERACTIONS

Front 62

Glycosaminoglycans aka Mucopolysaccharides

Back 62

Long Linear Polymers of Repeating Disaccharide Units

Front 63

Chondroitin Sulfate Found Where?

Back 63

Tendons
Ligaments
Ground Substance
Cartilage

Front 64

Dermatan Sulfate

Back 64

Skin
Blood Vessels
Heart Valve

Front 65

Heparin vs Heparan Sulfate Found Where?

Back 65

Heparin - IdoA - Intracellularly in Mast Cells

Heparan Sulfate - GlcA - Cell Surface, responsible for Lipoprotein Lipase binding

Front 66

Keratan Sulfate I & 2 Found Where?

Back 66

Cornea
Cartilage

Front 67

Proteoglycan Catabolism

Back 67

Critical Step = Removal of -SO4 by Sulfatase

Required for Action of Lysosomal Glycosidases (Can NOT Hydrolyze Sulfated Oligosaccharides)

Front 68

Glycoproteins

Back 68

Proteins to which Single Sugars OR Complex Polysaccharides are Covalently Bound

Primarily Extracellular OR Cell Surface Proteins

Front 69

Blood Types and Glycoprotein Differences

Back 69

Base = GlcNAc--Gal--Fuc

Type O: ""
Type B: Gal--Gal
Type A: Gal--GalNAc

Front 70

Sources of 1-C Units for Tetrahydrofolate (FH4)

Back 70

San Francisco Giants Have Freak

Serine
Formaldehyde
Glycine
Histidine
Formic Acid (Formate)

Front 71

Methyl Trap

Back 71

Once FH4 is fully reduced to N5-Methyl-FH4, it is trapped and can NOT be Reoxidized

Front 72

Role of 5-Methyl FH4

Back 72

Homocysteine --> Methionine

Front 73

Role of 5,10-Methylene FH4

Back 73

Two Reactions:

1) Glycine --> Serine
2) dUMP --> dTMP

Front 74

Reactions of Vit B12 aka Cobalamin (2):

Back 74

1) Homocysteine --> Methionine (FH4 also involved in this rxn, donates methyl to Vit B12)

2) Methylmalonyl CoA --> Succinyl CoA

Front 75

Reactions of SAM (5):

Back 75

1) Norepi --> Epi
2) Guanidinoacetate --> Creatine
3) Nucleotides --> Methylated Nucleotides
4) PE --> PC
5) Acetylserotonin --> Melatonin

Front 76

Rate Limiting Step of Heme Biosynthesis/Regulation

Back 76

ALA Synthase (Glycine + Succinyl CoA --> ALA)

Heme regulates in 2 ways:
1) REPRESSOR - Regulates Transcription of Gene for ALA Synthase

2) INHIBITOR - Regulates Activity of ALA Synthase

Front 77

Units Making Heme

Back 77

Glycine + Succinyl CoA --> ALA

2 ALA --> PBG

4 PBG --> Tetrapyrrole

Front 78

Heme Biosynthetic Steps INHIBITED by Lead (2):

Back 78

1) ALA --(ALA Dehydratase)--> PBG

2) Protoporphyrin IX --(Ferrochelatase aka Heme Synthase)--> Heme

Front 79

In what manner are Porphyrias OFTEN inherited?

Back 79

Autosomal DOMINANT!

Front 80

Acute Intermittent Porphyria

Back 80

Half Normal Activity of PBG Deaminase

PURPLE URINE!

INcreased PBG when Heme synthesis is stimulated, leading to peripheral neuropathy and CNS involvement

Also, severe abdominal pain.

Front 81

Congenital Erythropoietic Porphyria

Back 81

Autosomal Recessive! (Most Porphyrias are Auto Domiant)

Deficiency of Uroporphyrinogen III Cosynthase (Cant go into Heme biosynthetic pathway)

Increased Uroporphyrin I and Coproporphyrin I

Buildup of Non-Physiological Porphrins in Bone Marrow and Skin

Result: Damage to Erythrocytes and Cutaneous Photosensitivity

Front 82

Variegate Porphyria

Back 82

Common in White South Africans

Precipitated by same factors as Acute Intermittent Porphyria w/ Similar Symptoms + Photosensitivity

Symptoms rare before puberty.

Front 83

Conversion of Heme --> Bilirubin

Back 83

CLEAVE Methylene Bridge --> Biliverdin IX (Green)

REDUCE Methylene Bridge --> BiliRubin IX (Red)

Front 84

Crigler -Najjar Syndrome

Back 84

Inherited deficiency in Bilirubin UPD-Glucuronosyl Transferase (Bilirubin-Albumin --> Bilirubin-Diglucuronide)

Front 85

Direct vs Indirect Bilirubin Analysis

Back 85

Direct = Conjugated Bilirubin (NON-Protein Bound)

Indirect = Non-Conjugated Bilirubin (Protein Bound)

Front 86

Differences in Order of Purine/Pyrimidine Synthesis:

Back 86

Purine: Components of Base are added independently to PRPP

Pyrimidine: Base synthesized First (Orotate), THEN is added to PRPP

Front 87

Rate Limiting Step of Pyrimidine Synthesis/Regulation

Back 87

Carbomyl Phosphate Synthetase II (Glutamine/CO2/2 ATP --> Carbomyl Phosphate)

ACTIVATOR = PRPP
INHIBITOR = UTP

Front 88

Degradation of Pyrimidines:

Back 88

Broken down to Thymine and Uracil (NOT Cytosine!!!!)

Final Products:
Uracil-->Beta-Alanine
Thymine--> Beta-Aminoisobutyrate

Front 89

Vascular Cells and Vioxx

Back 89

Vascular Cells PGH2 Produces Prostacyclin (PGI2)

Prostacyclin Fx:
1) Inhibits Platelet Aggregation
2) Causes Vasodilation

Vioxx - Inhibits Vascular Cell PGHS2 (COX2) --> Decreased Prostacyclin (PGI2)

Front 90

Platelets and Celebrex

Back 90

Platelet PGH2 Produces Thromboxane A2 (TXA2)

Thromboxane A2 Fx:
1) Stimulates Platelet Aggregation
2) Causes Vasoconstriction

Celebrex - Inhibits Platelet PGHS2 (COX2) --> Decreased Thromboxane A2 (TXA2)

Front 91

Structural Differences Between Eicosanoids (3):

Back 91

ALL HAVE 20 Carbons!

1) Prostaglandins - 5 C Ring, -OH at C15

2) Thromboxane - 6 C Ring including an O

3) Leukotriene - 3 Conjugate Double Bonds

Front 92

Leukotriene Fx (3):

Back 92

1) Vascular Permeability

2) Leukocyte Proliferation

3) Bronchoconstriction (Singulair blocks Leukotriene receptors for Asthma patients)

Front 93

Common Sphingolipidoses Disorders (6):

Back 93

Accumulations of Varying Sphingolipids in Lysosomes

ALL Autosomal Recessive, EXCEPT FABRY's = X-Linked Recessive

TS F a M, KG, a N

Tay Sachs
Sandhoff

Fabry's

Metachromatic Leukodystrophy

Krabbe's
Gaucher's

Niemann-Pick

Front 94

ALL Primary Active Transporters are Phosphorylated on what Residue?

Back 94

Aspartate!

Front 95

Deficiency of what leads to Rickets?

Back 95

Vitamin D3

Front 96

--cide

Back 96

to kill

Front 97

Energy Contents of Fuels (4):

Back 97

kcal/gram

Carbohydrate = 4
Protein = 4
Alcohol = 7
Fat = 9

Front 98

Basal Metabolic Rate ~

Back 98

24 kcal/kg wt/day

1 kg = 2.2 lbs

Front 99

Recommended Daily Intakes:

1) Fat
2) Cholesterol
3) Protein

Back 99

1) 30% or Less of Total Calories

2) No More than 300 mg/Day

3) 0.8 Grams/Kg Body Weight/Day

Front 100

Protein Catabolic Rate (Grams/Day) =

Back 100

(24 Hour UUN (grams) + 4) X 6.25

UUN = Urinary Urea Nitrogen

Front 101

Kwashiorkor

Back 101

Inadequate Intake of PROTEINS with Adequate Calories

Front 102

Marasmus

Back 102

Chronic Deficiency of Calories

Front 103

Vitamin B1

Back 103

Thiamine (TPP)

Fx: AlphaKetoAcid Dehydrogenase; Transketolase

Deficiency = Beri-beri and Wernicke-Korsakoff Syndrome (confusion, ataxia, nystagmus, ophthalmoplegia, amnesia)