Biochem Exam 4 Diseases

Question 1

Celiac

Answer 1

gluten not fully digested–> autoimmune reaction

Question 2

cystinuria

Answer 2

defective membrane transporter in kindey glomeruli–> cysteine, arginine, citrulline, lysine excreted. excess cystine oxidized–> kidney stones

Question 3

Hartnups

Answer 3

defective tryp. transporter in kidney and intestins. Tryp used to make Niacin, B3 and NAD+. Dermatitis, dementia, diarrhea. Similar to pellagra (4 D’s)

Question 4

N-end rule

Answer 4

N-terminus affects half life of proteins. aminopeptidases do (N-terminal exopeptidase), carboxypeptidase do not (c-terminal exopeptidase)

Question 5

Kwashiorkor

Answer 5

lack protein–> flaky skin, bloated stomach = lost of albumin, loss of urea enzymes

Question 6

Ornithine Transcarbamoylase/OTC defect

Answer 6

X-linked is most common–> buildup of ornithine and carbamoyl phosphate in mitochondria.
Ornithine–> glutamic semi-aldehyde –> glutamate buildup
Carbamoyl phosphate in cytoplasm –> orotate and pyrimidine buildup

Question 7

HPV

Answer 7

E6 binds p53, recruits Ec ubiquitin ligase (defective in parkinsons). E7 sequesters Rb. HPV 16 and 18 involved with cervical cancer

Question 8

Parkinsons

Answer 8

parkin=E3 ubiquitin ligase. Lewy bodies= ubiquitin conjugation which depletes dopamine

Question 9

Orotic aciduria

Answer 9

pediatric. OMP decarboxylase or orotate phosphoribosyltranferase deficiency –> orotate buildup.
Tx- uridine nucleoside to make UMP

Question 10

PKU

Answer 10

dihydrobiopterin reductase (regenerates tetrahydrobiopterin) and phenylalanine hydroxylase deficiency’s –> phenylalanine buildup and tyrosine loss (it becomes and essential AA). Phenols excreted in urine

Question 11

Alcaptonuria

Answer 11

homogentisate oxidase deficiency. oxidation of homogentisate in joints–> arthritis and dark urine

Question 12

MSUD

Answer 12

Maple syrup urine disease

missing branched chain ketoacid DH–> VIM(T) buildup or Ile, Val, Leu + alpha-KB from Met and Thr

Question 13

Methylmalonic acidemia

Answer 13

defective methylmalonyl CoA mutase, lack B12/cobalamin, lack adenosyl B12, lack intrinsic factors
leads to ketoacidosis, muscular weakness, neurological defects (loss of myelin sheath)

Question 14

Albinism

Answer 14

tyrosinase defect–> no melanin, light skin/hair/eyes

blindness

Question 15

Homocysteinuria

Answer 15

defective cystathionine synthetase–> arterial, thrombotic disease, tall + thin, vision problems

Question 16

Homocysteinuria Tx

Answer 16

Folate, cystein, choline supplements
PLP/B6 supplements–> cystothionine synthetase
less Methionine–> less homocysteine produced
low protein diet

Question 17

Gout

Answer 17

high uric acid levels, crystal depositis in cartilage, joints, kidneys.

1) partial def. HGPRT => reduced IMP, GMP =>not feedback inhibited. +PRPP => de novo purine synthesis. 2) PRPP not sensitive to feedback inhibition => PRPP => de novo purine synthesis
3) def. glucose-6-phosphatase => increased pentose phosphate activity => ribose-5P => PRPP

Question 18

Lesch-Nyhan Syndrome

Answer 18

No HGPRT. self mutilation, mental illness (high HGPRT in brain normally), gout.

Question 19

Adenosine Deaminase Deficiency

Answer 19

Adenosine nucleoside buildup => increased dATP => inhibited ribonucleotide reductase => severe combined immunodeficiency (SCID) = no B or T cells

Question 20

Allopurinol (Treatment for gout)

Answer 20

ypoxanthine analogue => comp. inhibitor of xanthine oxidase = reduce uric acid level.

Question 21

Sulfonamide

Answer 21

p-aminobenzoate analogue => inhibit bacterial folate biosynthesis. (Folate is needed in thymidylate, methionine synthesis)

Question 22

6-Mercaptopurine

Answer 22

hypoxanthine analogue uses HGPRT => nucleotide analogue (decreased IMP) Uses up PRPP => Decreased de novo purine synthesis => decreased AMP/GMP

Question 23

Methotrexate

Answer 23

Folate analogue => irreversible binds dihydrofolate reductase => unable to regenerate THF Usage: childhood leukemia, psoriasis. Also kills rapidly dividing cells like bone marrow, intestine, hair?

Question 24

5-Fluorodeoxyuridine (suicide inhibitor)

Answer 24

thymidine kinase converts to nucleotide fdUMP (similar to AZT=>AZT triphosphates) fdUMP = dUMP analogue = binds/inhibits thymidylate synthetase => inhibited production of dTMP

Question 25

Hydroxyurea

Answer 25

binds tyrosyl radical => inhibit ribonucleotide reductase

Question 26

B-aminoisobutyrate

Answer 26

Thymine catabolism = soluble/urine = monitor DNA/cell destruction in chemotherapy

Question 27

Benzoate

Answer 27

conjugate glycine => excretion = remove excess nitrogen

Question 28

Phenylacetate/Phenylbutyrate

Answer 28

conjugate glutamine => excretion = remove excess nitrogen

Question 29

Biotin

Answer 29

Propionyl CoA carboxylase (Propionyl CoA =>D-methylmalonylCoA) Part of VIM(T) to succinyl CoA catabolic pathway

Question 30

Tetrahydrobiopterin

Answer 30

Phenylalanine hydroxylase (Phenylalanine => Tyrosine) Tyrosine hydroxylase (Tyrosine => Dopa)

Question 31

PLP/B6

Answer 31

Transaminases
Dopa Decarboxylase (Dopa => Dopamine)
Cystathione Synthetase (Homocysteine => Cystathione)

Question 32

Methyl B12

Answer 32

Methionine Synthase (5-methyl THF + homocysteine => THF + Methionine)
Deficiency => unable to regenerate THF from most reduced 5-methyl THF (folate trap/deficiency)

Question 33

Adenosine B12

Answer 33

Methylmalonyl CoA Mutase (L-methylmalonyl CoA => Succinyl CoA)
Deficiency => Methylmalonic acidemia