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Flashcards in Biochemistry - Part 2 - More important concepts Deck (74)
1

What enzyme defect causes PKU?

Either defect in phenylalanine hydroxylase (more common) or defect in dihydrobiopterin reductase (regenerates BH4 from BH2).

2

What is the musty / mousy odor in PKU due to?

Accumulation of abnormal phenylalanine metabolites

3

Severe intellectual disability, seizures, respiratory failure in a young boy with substantia nigra, locus ceruleus, vagal nucleus dorsalis pallor

PKU

4

Phenyllactate

A phenylalanine metabolite, along with phenylacetate, which accumulates in PKU and contributes to the brain damage

5

Path from tyrosine to the TCA cycle

Tyrosine -->homogentisate -(homogentisic acid oxidase)-> maleylacetoacetate -> fumarylacetoacetate -> fumarate -> TCA

6

What are the branched chain amino acids?

I Love Vermont Maple syrup - Isoleucine, leucine, Valine

7

What enzyme catalyzes decarboxylation of the alpha-ketoacid derivatives of the branched chain amino acids?

Branched chain ketoacid dehydrogenase

8

Ptosis, orthostatic hypotension, hypoglycemia, hypothermia

Defect in dopamine hydroxylase

9

Homogentisic acid oxidase

Catalyzes the degradation of tyrosine

10

Autosomal recessive disorder of tyrosine degradation caused by deficiency of homogentisic acid oxidase. Accumulation of large amounts of homogentisic acid. Connective tissue hyperpigmentation, degenerative joint disease.

Alkaptonuria

11

Depressed or absent tyrosinase activity leads to...

Albinism

tyrosine --> DOPA -(tyrosinase)-> dopaquinone

12

Conservative mutation

Missense mutation where one amino acid is replaced with another amino acid with similar biochemical characteristics

13

Deficiency of alpha-galactosidase A

Fabry disease

14

Accumulation of ceramide trihexoside

Fabry disease

15

Hypohidrosis, acroparesthesia, angiokeratomas... and without enzyme replacement, renal insufficiency and renal failure and death.

Fabry disease

16

Acroparesthesia

Episodic, debilitating, neuropathic pain in the extremities

17

Angiokeratoma

Punctate, dark red, nonblanching macule and papule that occur between umbilicus and knees

18

Acute leukemia is associated with which genetic disorders?

Down syndrome
Patau syndrome
Ataxia telangiectasia
Bloom syndrome
Fanconi syndrome

19

Classic Galactosemia

Caused by impaired galactose-1-phosphate uridyl transferase (GALT) which converts Galactose 1P to UDP-galactose (transfers UDP from UDP-glucose)

20

Galactosyl beta-1, 4 glucose

Another name for lactose

21

Vomiting, lethargy, failure to thrive soon after breastfeeding is begun
Hyperchloremic metabolic acidosis, amino aciduria, impaired liver function.
Irreversible eye and liver damage from galactitol accumulation

Galactosemia

22

Galactokinase deficiency

Less severe; may cause cataracts?

23

PRPP synthetase gene increased activation

Leads to increased purine synthesis pathway and degradation --> increased gout risk.

24

What cells are responsible for the intense inflammatory response seen with gout?

Neutrophils - phagocytosis of urate crystals leads to release of various cytokines and inflammatory mediators that lead to further neutrophil activation and chemotaxis, resulting in a positive feedback loop that amplifies the inflammatory response.

25

What is the treatment for gout?

NSAIDs are first line because they inhibit prostanoid biosynthesis through COX2 I believe.

Colchicine - decreases tyrosine phosphorylation in response to monosodium urate, resulting in decreased neutrophil activation. Inhibits neutrophil chemotaxis and phagocytosis by preventing microtubule formation.

26

Growth hormone receptors act through what pathway?

JAK-STAT.
Attach to extracellular domain of growth homrone receptor --> dimerization --> conformation change of JAK --> tyrosine kinase activity --> STAT transcription activity

27

Vitamin deficiency after 4 years?

Cobalamin

28

How long does Vitamin A last?

6 months - contained in perisinusoidal stellate Ito cells of the liver

29

How long does folate last?

3-4 months, liver contains half of the body's folate.

30

Vitamin K - how long does it last?

1-3 weeks.

31

Lynch syndrome - HNPCC - which genes are mutated?

MutS or MutL

32

Severe fatigue, splenomegaly (often causing early satiety/abdominal discomfort), hepatomegaly, anemia, bone marrow fibrosis

Primary myelofibrosis - JAK2 mutation

33

Pruritis, erythromelalgia, splenomegaly, thrombotic complication, erythrocytosis, thrombocytosis

Polycythmia vera - JAK2 mutation

34

Hemorrhagic and thrombotic symptoms (easy bruising, microangiopathic occlusion, thrombocytosis and megakaryocytic hyperplasia)

Essential thrombocytosis - JAK2 mutation

35

Constitutional sx (fatigue, wt loss, excessive sweating), splenomegaly, leukocytosis with left shift (myelocytes, metamyelocytes, band forms)

BCR:ABL - CML

36

JAK2 inhibitor approved for treatment of primary myelofibrosis

Ruxolitinib

37

Valine --> Phenylalanine at 617 in JAK2

Constitutive tyrosine phosphorylation activity leading to the chronic myeloproliferative disorders

38

15;17 translocation in acute promyelocytic leukemia

Leads to PML and retinoic acid receptor alpha fusion gene which blocks differentiation of myeloid precursors.

39

EGF, PDGF, FGF signal through...

MAP Kinase - receptor autophosphorylates and triggers phosphorylation of ras

40

First step in glycogen degradation

1,4 glycosidic linkage to form glucose-1-phosphate

41

How do you convert pyruvate to PEP for gluconeogenesis?

pyruvate --> oxaloacetate through pyruvate carboxylase
oxaloacetate --> malate (malate dehydrogenase in mitochondria)
malate --> oxaloacetate (cytosolic malate dehydrogenase)
oxaloacetate --> PEP (phosphoenolpyruvate carboxykinase - PEPCK)

42

What enzymes differ between glycolysis and gluconeogenesis?

pyruvate -> PEP
fructose 1,6 bisphosphatase (bypasses phosphofructokinase)
glucose-6-phosphatase (bypasses hexokinase)

43

How do aminoglycosides work?

Impair INITIATION of protein synthesis and inhibit formation of INITIATION complex.
Bind 30S

44

How do tetracyclines work?

Interfere with amino-acyl-tRNA binding to the A site

45

Acetyl CoA carboxylase

Biotin dependent enzyme in liver and adipose tissue that catalyzes the first committed step in fatty acid synthesis, which occurs in the cytosol.

46

Where does fatty acid oxidation occur?
Where does fatty acid synthesis occur?

Oxidation - Mitochondria
Synthesis - Cytosol

47

Fetal hemoglobin

alpha 2 gamma 2

48

Hemoglobin A2

alpha 2 delta 2

49

earliest hemoglobin found in the fetus?

Hemoglobin gower, zeta 2 epsilon 2, synthesized in the yolk sac --> hemoglobin portland --> hemoglobin gower 2 --> hemoglobin F at 10-12 weeks

Wow!

50

Hemoglobin Bart

4 gamma proteins (gamma 4).
Found in homozygous alpha thalassemia
High affinity for oxygen and does not release it to the tissues --> tissue hypoxia.

51

NO comes from which AA?

Arginine ("Argh! NO!")

52

Urea comes from which AA?

Arginine + aspartate

53

Heme comes from which AA?

Glycine + succinyl CoA

54

Creatinine comes from what things?

Glycine + arginine + SAM

55

GABA comes from which AA?

Glutamate

56

Glutathione comes from which AA?

Glutamate

57

Pyrimidines come from which AA?

Glutamate + aspartate

58

Purines come from which AA?

Glutamate + aspartate + glycine (GAG)

59

Niacin comes from which AA?

Tryptophan ("toe fan")

60

Thyroxine comes from which AA?

Tyrosine

61

Melanin comes from which AA?

Tyrosine

62

eNOS - endothelial nitric oxide synthase - synthesizes nitric oxide from what?

Arginine, NADPH, and O2

63

Which processes occur outside the cell in collagen synthesis?

Terminal propeptides cleaved by N and C-procollagen peptidases.
Collagen molecules spontaneously assemble.
Covalent cross-links formed by lysyl oxidase.

64

Pre-pro-alpha chain

Newly synthesized, unmodified alpha chain (first step in collagen synthesis)

65

Pro-alpha chain

After hydrophobic signal peptide at N terminus is cleaved from the pre-pro-alpha chain (collagen formation)

66

Procollagen molecule

Triple collagen helix which has had disulfide bond formation, hydroxylation of proline and lysine residues.

67

Sideroblastic anemia enzyme

d-aminolevulinate synthase, requires B6

68

Heme in liver versus heme in bone marrow

Liver --> used for cytochrome p450 system
Bone marrow --> used for hemoglobin

69

AIP enzyme

Porphobilinogen deaminase

70

Heme negatively feedback inhibits what?

ALA synthase

Reduction in heme synthesis leads to increased d-aminolevulinic acid and porphobilinogen which lead to acute abdominal pain and neurologic sx.

71

What does lead inhibit?

ALA dehydradatase and ferrochelatase

72

Zellweger syndrome

Infants are unable to properly form myelin in the CNS.
Hypotonia and seizures, hepatomegaly, mental retardation, early death within months

73

Refsum disease

Defect in peroxisomal alpha oxidation --> neurological disturbances in response to accumulation of phytanic acid within the body. Strictly avoid chlorophyll in the diet.

74

Where are very long chain fatty acids oxidized?

Peroxisomes