Usmle Step 1 - April 27 & 30 (Biochem)

Front 1

What is AFP? What is its significance diagnostically?

Back 1

α-Fetoprotein:

Glycoprotein ~ like a fetal albumin;
Binds = Ni, Cu, FA's & bilirubin

Dx tool for pregnancy:
- ↑ AFP = Neural tube defects & omphalocele
- ↓ AFP = Down syndrome

Dx tool in children:
- ↑ AFP = Ataxia-telangiectasia (8 months)

Dx tool in adults:
- ↑ AFP = HCC & Mets, Germ cell tumors

Front 2

X-Linked Immunodeficiencies?

Back 2

WBC

W- Wiskott-Aldrich
B- Bruton's agammaglobulinemia
C- Chronic granulomatous disease

Front 3

What are the X-Linked Recessive Disorders?

Back 3

1) Immunodeficiencies (WBC's)
- W - Wiskott-Aldrich
- B - Bruton's Agammaglobulinemia

2) Lysosomal Storage:
- Fabry's (sphingo)
- Hunter's (mucopolysacc)

3) Enzyme deficiencies:
- G6PD-deficiency
- Lesch-Nyhan (HGPRT)

4) Muscular dystrophy (dystrophin)
- Duchenne's (delete)
- Becker's (mutation)

5) Hemophilia
- A - F VIII
- B - F IX

6) Ocular albinism
7) Fragile X

Front 4

What recurrent infections are people w/ CF prone to?

Back 4

Pseudomonas
Staph aureus

NOTE: this is the case where you would use fluoroquinolones in kids (d/t pseudomonas risk)

Front 5

What is Duchenne's muscular dystrophy?

Back 5

an XLR dz caused by frameshift mutation that deletes the dystrophin gene (DMD).

Results in accelerated muscle breakdown (pelvic girdle first --> superiorly).

Front 6

What are the signs of Duchenne's muscular dystrophy?

Back 6

1) Muscle weakness (beginning @ pelvic girdle and moving superiorly)

2) Labs = ↑CPK

3) Gower's maneuver - using hands to stand up

4) Pseudohypertrophy of calf muscles (pseudo- d/t fibrofatty replacement of muscle)

5) Usually young (onset b4 5 y/o)

Front 7

What is Becker's muscular dystrophy?

Back 7

X-Linked recessive mutation of the dystrophin gene.

Less severe disease than duchenne's and later onset (adolescence --> adulthood)

Front 8

What is Fragile X syndrome and what does it cause?

Back 8

X-Linked recessive disease affecting the FMR1 gene.

It is a Trinucleotide repeat disorder (CGG).

Findings:
1) X-tra large:
- testes
- jaw
- ears
2) MR - autism
3) MVP

Front 9

What is the FMR Protein?

Back 9

Coded by FMR1 gene, affected in Fragile X Syndrome.

1) Is a cytoplasmic protein found in:
- Brain → MR
- Tetes → macroorchidism

2) Involved in mRNA translation in:
- axons
- dendrites

Front 10

What is the cause of 95% of cases of Down syndrome?

Back 10

Meiotic nondisjunction of homologous chromosomes
(a/w advanced maternal age)

Front 11

What condition would be associated with an ↓AFP, ↑hCG, ↓E3, ↑inhibin A?

Back 11

Down syndrome

Front 12

What condition would be a/w ↑ nuchal translucency?

Back 12

Down syndrome
Turner syndrome

Front 13

What condition would be associated with ↓AFP, ↓HCG, ↓E3 and normal inhibin A?

Back 13

Edward's syndrome
Trisomy 18

Front 14

What chromosomes are particularly involved in robertsonian translocation?

Back 14

13, 14, 15
21, 22

Front 15

What condition is a/w high pitched crying and mewing?

Back 15

Cri-du-chat syndrome
Microdeletion of short arm of chromosome 5 (5p-)

Also a/w:
- microcephaly
- moderate → severe MR
- epicanthal folds
- cardiac (VSD)

Front 16

What is William's syndrome?

Back 16

Microdeletion of long arm of chromosome 7 (elastin gene)

a/w:
- Elfin facies
- MR
- Hypercalcemia (sens. to VitD)
- Extreme friendliness to strangers
- CV problems

think Will Ferrel in Elf

Front 17

What are the presentations of 22q11 deletion syndromes?

Back 17

CATCH-22 (3,4)

C - Cleft palate (2º palate)
A - Abnormal facies
T - Thymic aplasia
C - Cardiac defects
H - Hypocalcemia (2º d/t parathyroid aplasia)

Front 18

What are examples of 22q11 deletion syndromes?

Back 18

DiGeorge syndrome
Velocardiofacial syndrome

Front 19

What is the rate-limiting enzyme of glycolysis?

Back 19

PFK1 = phosphofructokinase-1

Front 20

What is the rate-limiting enzyme of gluconeogenesis?

Back 20

F16BP = fructose-1,6-bisphosphatase

Front 21

What is the rate-limiting enzyme of TCA cycle?

Back 21

Isocitrate dehydrogenase

Front 22

What is the rate-limiting enzyme of glycogen synthesis?

Back 22

Glycogen synthase

Front 23

What is the rate-limiting enzyme of glycogenolysis?

Back 23

Glycogen phophorylase

Front 24

What is the rate-limiting enzyme of the HMP shunt?

Back 24

G6PD = glucose-6-phosphate dehydrogenase

Front 25

What is the rate-limiting enzyme of de novo pyrimidine synthesis?

Back 25

CPS II = carbamoyl phosphate synthetase II

Front 26

What is the rate-limiting enzyme of de novo purine synthesis?

Back 26

Glutamine-PRPP amidotransferase

Front 27

What is the rate-limiting enzyme of the Urea cycle?

Back 27

CPS I = carbamoyld phosphate synthetase I

Front 28

What is the rate-limiting enzyme of fatty acid synthesis?

Back 28

ACC = acetyl-coA carboxylase

Front 29

What is the rate-limiting enzyme of fatty acid oxidation?

Back 29

CAT I = carnitine acyltransferase I

Front 30

What is the rate-limiting enzyme of ketogenesis?

Back 30

HMG-CoA synthase

Front 31

What is the rate-limiting enzyme of cholesterol synthesis?

Back 31

HMG-CoA reductase

Front 32

What is the difference between glucokinase and hexokinase?

Back 32

Hexokinase is ubiquitous
- high affinity (low Km) BUT
- low capacity (low Vm)
- negative f/b from its product (G6P)

Glucokinase in liver & ßCells
- low affinity (high Km)
- high capacity (high Vm)
- allows liver to be glucose "buffer" and store excesses

Front 33

What is the activated carrier for methyl groups?

Back 33

SAM = s-adenosyl methionine

ATP + methionine → SAM
SAM transfers methyl units for anabolic pathways:
- phophocreatine
- NE → EPI

leaves homocysteine which is regenerated to methionine by:
- B12
- THF

Front 34

What is the main function of biotin?

Back 34

To act as a cofactor for carboxylation enzymes (adding C from CO2)

Front 35

What steps in glycolysis require ATP?

Back 35

1) Hexokinase/glucokinase

2) Phophofructokinase-1
(rate limiting step)

Front 36

What steps in glycolysis generate ATP?

Back 36

1) Phosphoglycerate kinase

2) Pyruvate kinase

3) Pyruvate dehydrogenase

Front 37

What stimulates/inhibits PFK-1?

Back 37

Stimulates:
- AMP
- F2,6BP

Inhibits:
- ATP
- Citrate

Front 38

What stimulates/inhibits Pyruvate kinase?

Back 38

Stimulates:
- F16BP

Inhibits:
- ATP
- Alanine

Front 39

What is the effect on F26BP in the fasting state?

Back 39

Fasting → ↑PKA → ↑ FBP2

This converts F26BP back to F6P and removes stimulation of PFK-1; therefore there is less glycolysis

Front 40

What is the effect on F26BP in the fed state?

Back 40

Fed state → ↓PKA → ↑PFK-2

This generates more F26BP which in turn upregulates PFK-1 and there is more glycolysis

Front 41

How does PKA affect glycolysis?

Back 41

PKA is either stimulated by cAMP (d/t ↑glucagon) or inactivated by low cAMP (↑insulin).

When active, PKA phophorylates the PFK2/FBP2 complex.

Phosphorylation activates FBP2 -> converts F26BP to F6P

Front 42

What are the irreversible enzymes of gluconeogenesis, their location in the cell, and any cofactors?

Back 42

1) Pyruvate carboxylase
- mitochondria
- biotin + ATP

2) PEP carboxkinase
- cytosol
- GTP

3) Fructose-1,6-bisphosphatase
- cytosol
- RATE LIMITING STEP

4) Glucose-6-phosphatase
- ER
- (deficiency = von Gierke's dz)

Front 43

What is von Gierke's disease?

Back 43

A deficiency in Glucose-6-phosphatase.

This prevents the final step of gluconeogenesis (the "liver acts like a muscle" b/c it lacks this crucial enzyme)

Front 44

What are the glycogen storage diseases?

Back 44

Very Poor Carbohydrate Metabolism

V - Von Gierke's
P - Pompe's
C - Cori's
M - McArdle's

Front 45

What are the four fates of pyruvate?

Back 45

1) Alanine shuttle (ALT)
2) Gluconeogenesis (Pyruvate carboxylase & PEP carboxykinase)
3) TCA (PDH = pyruvate dehydrogenase)
4) Lactate (LDH)

Front 46

What are the cofactors of the Pyruvate dehydrogenase complex?

Back 46

TLC For No-one:

T - Thiamine (B1)
L - Lipoic acid
C - CoA (B5)
F - FAD (B2)
N - NAD (B3)

NOTE: same cofactors as α-ketogluterate dehydrogenase complex

Front 47

What are the major enzymes of the TCA?

Back 47

1) PDH = pyruvate dh (3C → 2C)
2) IDH = isocitrate dh (6C → 5C)
3) αDH = α-Ketoglutarate dh (5C → 4C)

NOTE: all generate CO2 & NADH

Front 48

What does each turn of the TCA generate (per pyruvate)?

Back 48

Pyr → A-CoA:
- 1 x CO2
- 1 x NADH

TCA cycle:
- 2 x CO2
- 3 x NADH
- 1 x FADH2
- 1 x GTP
- 12 x ATP

Front 49

What are the results and treatment of pyruvate dehydrogenase deficiency?

Back 49

Lactic acidosis (and buildup of pyruvate)

Findings = neurological defects

Tx = ↑ ketogenic nutrients
- high fat
- lysine
- leucine

Causes can be d/t B1 (thiamine deficiency) d/t:
- nutritional
- EtOH addiction

Front 50

What are pathology signs of G6PD deficiency?

Back 50

Heinz bodies = oxidized Hb
Bite cells = phagocytized removal of heinz bodies in spleen by macrophages

Front 51

What does G6PD do?

Back 51

Generates NADPH (reduces NADP+) which is used to regenerate oxidized glutathione that can convert H2O2 → H2O
(prevent oxidative damage)

Front 52

What are the drugs that can cause hemolytic anemia in someone w/ G6PD deficiency?

Back 52

Hemolysis IS PAIN:
I - INH
S - Sulfonamides
P - Primaquine
A - ASA
I - Ibuprofen
N - Nitrofurantoin (abx)

also: Fava beans and anti-TB's

Front 53

What are the symptoms of fructose inctolerance? What is the cause?

Back 53

Symptoms:
- Cirrhosis
- Jaundice
- Hypoglylcemia
- Vomiting

d/t Aldolase B deficiency
(FAB GUT)

Front 54

What are the symptoms of galactosemia? What is the cause?

Back 54

Symptoms:
- FTT (failure to thrive)
- Hepatomegaly
- Jaundice
- MR
- Cataracts (infantile)

d/t Uridyl-Transferase deficiency
(FAB GUT)