Biochem

Question 1

Pt presents with self mutilation, mental retardation, dystonia, and gout.
What is elevated in blood stream?
What is mechanism?

FA 64

Answer 1

Results in excess uric acid production and de novo purine synthesis.

Defective purine salvage due to absent HGPRT:
converts Hypoxanthine into IMP
converts Guanine into GMP

X-linked recessive. Lesch-Nyhan syndrome

Question 2

Pt with joint pain and hematuria has rhomboid crystals are in urine as well as hyperuricemia.
How to treat the urine crystals?
How would you treat the pt’s joint pain that they are having and what’s its mechanism?

Answer 2

Uric acid precipitates at acidic / low pH. Treatment is alkalinization of urine. (FA 544)

Treat gout with allopurinol which blocks xanthine oxidase to stop hypoxanthine from being converted into uric acid (FA 64)

Question 3

Child is found to have cherry-red spots on macula as well as progressive neurodegeneration, hepatosplenomegaly, and foam cells.
What is the enzyme deficiency?

Answer 3

Classic presentation with Cherry red macula of either Tay-Sachs or Niemann-Pick (FA 624)

Niemann-Pick has hepatosplenomegaly and lipid-laden macrophages.
Enzyme deficiency is sphingomyelinase resulting in accumulation of sphingomyelin.

Question 4

Cherry-red spot on macula found.

What is differentiation symptom between Niemann-Pick and Tay-Sachs disease?

Answer 4

Niemann-Pick has hepatosplenomegaly (sphingomyelinase deficiency) (FA 111)

Question 5

Pt with developmental delay, gargoylism, and hepatosplenomegaly is found to have abnormal urine sample.
What is in urine sample / is the accumulated substance?
What could be the two diseases?

Answer 5

Heparan sulfate and dermatan sulfate. (FA 111)

Hurler syndrome
vs
Hunter syndrome (no corneal clouding)

Question 6

Child boy with gargoylism, hepatosplenomegaly, and no corneal clouding is found to have elevated heparan sulfate and dermatain sulfate.

Enzyme deficiency? Inheritance?

Answer 6

Hunter syndrome: Iduronate sulfatase deficiency.

X-linked recessive. (FA 111)

Question 7

Draw out diagram of lysosomal storage diseases

at top: GM2

Answer 7

FA 111

Question 8

Classical symptoms of Gaucher disease.

Enzyme deficiency?

Answer 8

FA 111, 625
10 y/o pt with:
Hepatosplenomegaly
Pancytopenia (anemia, leukocytopenia)
osteoporosis 
aseptic necrosis of femur ('flask' looking)
Bone section taken and histo slide is shown: Shows crumpled tissue paper macrophages
Enz: Glucocerebrosidase

Question 9

Findings of Fabry

Enzyme deficiency

Answer 9

Peripheral neuropathy of hands/feet
angiokeratomas
cardiovascular/renal disease 
alpha - galactosidase A
FA 111

Question 10

10 y/o pt with angiokeratomas, peripheral neuropathy of hands and feet, and heart problems.
What enzyme deficiency?
Accumulated substrate?

Answer 10

alpha galactosidase A
ceramide trihexosidase
FA 111

Question 11

Classic presentation of Niemann-Pick disease

enzyme deficiency

Answer 11

sphingomyelinase deficiency
child pt with hepatosplenomegaly
foam cells (lipid-laden macrophages)
cherry red spot on macula
FA 111, 626

Question 12

Hereditary nonpolyposis colorectal cancer
enzyme deficiency
what part of cell cycle

Answer 12

defective mis match repair enzymes
G2
FA 67, p 113

Question 13

Colorectal cancer arises de novo (not from adenomatous polyp), young age, and on right side

Answer 13

defective mismatch repair enzyme, G2
hereditary nonpolyposis colorectal cancer
FA 67, p113

Question 14

Rifampin

Answer 14

inhibits prokaryotic RNA polymerase

FA 68

Question 15

Amanita phalloides

Answer 15

death cap mushroom
alpha amanitin toxin which inhibits RNA polymerase II
hepatotoxicity
FA 68

Question 16

Actinomycin D

Answer 16

inhibits RNA polymerase in both prokaryotes and eukaryotes
chemotherapeutic
FA 68

Question 17

Pt with butterfly rash, endocarditis, fever, arthritis.

antibody testing is done. what are these antibodies specific against and what is its role?

Answer 17

anti smith antibodies are specific against spliceosomal snRNP’s.
these remove introns as Lariat-shaped bodies
FA 69

Question 18

What is on the 3’ end of tRNA? (aminoacyl end)

what direction is the anticodon?

Answer 18

CCA on 3’ end, and amino acid is added here by aninoacyl-tRNA synthetase. 5’-CCA-3’
anticodon is 3’-5’ match to the 5’-3’ codon
FA 70

Question 19

mRNA start codon

what does it code for

Answer 19

AUG
codes for methionine in eurkaryotes
codes for fMet (N formylmethionine) in prokaryotes)

Question 20

mRNA stop codons

Answer 20

UGA, UAA, UAG
U Go away
U are away 
U are gone 
FA 67

Question 21

mRNA start codon for prokaryotes

what is special about it

Answer 21

AUG codes for fMet
this is a neutrophil chemotaxic agent
FA 67

Question 22

genetic difference between duchenne’s and becker’s muscular dystrophy

Answer 22

duchenne is frameshift insertion mutation of dystrophin gene
becker’s is non-frameshit insertion
fA 85

Question 23

Child pt has calf psuedohypertrophy and has gower’s sign

Inheritance?

Answer 23

Frameshift mutation (not divisible by 3)
X-linked recessive
Duchenne’s Muscular Dystrophy, mutation of dystrophin gene
FA 624, 85, 66

Question 24

Shigella and enterohemorrhagic E. coli (EHEC) release what toxins?
what is mechanism of these toxins?

Answer 24

Shiga toxin and shiga-like toxin
inactivate 60S ribosome by removing adenine from rRNA
FA 124,

Question 25

symptoms of shigella? Toxin? What is the mechanism?

Answer 25

GI mucosal damage -> dysenterry enhances cytokine release, causing hemolytic uremic syndrome (HUS) Findings: schistocytosis, renal insufficiency (thrombi), fever, thrombocytopenia with increased bleeding time, NL PT/PTT, megakaryocytes on BM biopsy poma 33, FA 124

Question 26

Mechanism of diphtheriae toxin

Answer 26

inactivates elongation factor (EF-2) via ADP-ribosylation of EF-2 Ribosome moves peptidyl tRNA to P-site (translocation) during elongation FA 124, 71

Question 27

Mechansim of exotoxin A | what bacteria releases it?

Answer 27

ADP-ribosylation of EF-2 Ribosome moves peptidyl tRNA to P-site (translocation) during elongation FA 124, 71

Question 28

Neomycin is used for bowel surgery. what type of bacteria is it used against? What is the mechanism?

Answer 28

gram-negative rods | bctericidal; irreversible inhibition of initiation complex thru binding of 30s subunit

Question 29

child presents with coarse facial features, clouded corneas, and restricted joint movement. Suspect Hurler's, but urine does not show ________ or ______ and blood result is high in lysosomal enzymes enzyme defect? mechansim?

Answer 29

Hurler: heparan sulfate, dermatan sulfate in urine Enz: N-acetylclugosaminyl-1-phosphotransferase Golgi cannot phosphorylate mannose residues (decreased mannose-6-phosphate) on glycoproteins FA 73, FA 111

Question 30

High glycine content in fibroblasts suggests synthesis of what?

Answer 30

collagen; Gly-X-Y wound repair fa 76

Question 31

Swollen gums, mucosal bleeding, poor wound healing, petechiae

Answer 31

Scurvy vitamin C deficiency; cannot hydroxylate proline/lysine for collagen synth FA 628, 76, 93

Question 32

Blue scera, multiple fractures in child | what organelle

Answer 32

``` osteogenesis imperfect (AD) defect in collagen I synthesis glycosylation in rough endoplasmic reticulum FA 624, 76, 75 ```

Question 33

Ehlers danlos Clinical presentation deficiency in what

Answer 33

elastic skin, hypermobility of joints, increased bleeding tendency collagen type V deficiency (III in vascular type) FA 625, 77

Question 34

elastic skin, hypermobility of joints what heart defect? could lead to what vascular emergency?

Answer 34

Mitral valve prolapse (MVP) Ehlers-Danlos (defective collagen synthesis / cross-linking, AD or AR) berry and aortic aneurysm FA 77, 625

Question 35

kinky hair, growth retardation, hypotonia what gene protein defect? mechanism?

Answer 35

Marfan, XLR ATP7A - can't absorb Cu2+, necessary for lysyl oxidase and cross-linkage of collagen FA 77

Question 36

Type IV collagen where is it found? What diseases?

Answer 36

Basement membrane, basal lamina, Lens. Alport syndrome (XLR mutation) FA 541 Goodpasture's (autoantibody, leading to what? FA 541) FA 75

Question 37

Hereditary nephritis, sensorineural hearing loss, cataracts

Answer 37

``` Alport syndrome (collagen IV mutation) FA 626, 75, 541 ``` "can't seen can't pee, can't hear a buzzing bee"

Question 38

Adrenoleukodystrophy

Answer 38

XLR. Disrupted metabolism of very-long chain fatty acids -> build up in nervous system, adrenal gland, testes long term coma/death and adrenal gland crisis FA 489