Biochem Exam 4 Diseases Flashcards
Celiac
gluten not fully digested–> autoimmune reaction
cystinuria
defective membrane transporter in kindey glomeruli–> cysteine, arginine, citrulline, lysine excreted. excess cystine oxidized–> kidney stones
Hartnups
defective tryp. transporter in kidney and intestins. Tryp used to make Niacin, B3 and NAD+. Dermatitis, dementia, diarrhea. Similar to pellagra (4 D’s)
N-end rule
N-terminus affects half life of proteins. aminopeptidases do (N-terminal exopeptidase), carboxypeptidase do not (c-terminal exopeptidase)
Kwashiorkor
lack protein–> flaky skin, bloated stomach = lost of albumin, loss of urea enzymes
Ornithine Transcarbamoylase/OTC defect
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
HPV
E6 binds p53, recruits Ec ubiquitin ligase (defective in parkinsons). E7 sequesters Rb. HPV 16 and 18 involved with cervical cancer
Parkinsons
parkin=E3 ubiquitin ligase. Lewy bodies= ubiquitin conjugation which depletes dopamine
Orotic aciduria
pediatric. OMP decarboxylase or orotate phosphoribosyltranferase deficiency –> orotate buildup.
Tx- uridine nucleoside to make UMP
PKU
dihydrobiopterin reductase (regenerates tetrahydrobiopterin) and phenylalanine hydroxylase deficiency’s –> phenylalanine buildup and tyrosine loss (it becomes and essential AA). Phenols excreted in urine
Alcaptonuria
homogentisate oxidase deficiency. oxidation of homogentisate in joints–> arthritis and dark urine
MSUD
Maple syrup urine disease
missing branched chain ketoacid DH–> VIM(T) buildup or Ile, Val, Leu + alpha-KB from Met and Thr
Methylmalonic acidemia
defective methylmalonyl CoA mutase, lack B12/cobalamin, lack adenosyl B12, lack intrinsic factors
leads to ketoacidosis, muscular weakness, neurological defects (loss of myelin sheath)
Albinism
tyrosinase defect–> no melanin, light skin/hair/eyes
blindness
Homocysteinuria
defective cystathionine synthetase–> arterial, thrombotic disease, tall + thin, vision problems
Homocysteinuria Tx
Folate, cystein, choline supplements
PLP/B6 supplements–> cystothionine synthetase
less Methionine–> less homocysteine produced
low protein diet
Gout
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
Lesch-Nyhan Syndrome
No HGPRT. self mutilation, mental illness (high HGPRT in brain normally), gout.
Adenosine Deaminase Deficiency
Adenosine nucleoside buildup => increased dATP => inhibited ribonucleotide reductase => severe combined immunodeficiency (SCID) = no B or T cells
Allopurinol (Treatment for gout)
ypoxanthine analogue => comp. inhibitor of xanthine oxidase = reduce uric acid level.
Sulfonamide
p-aminobenzoate analogue => inhibit bacterial folate biosynthesis. (Folate is needed in thymidylate, methionine synthesis)
6-Mercaptopurine
hypoxanthine analogue uses HGPRT => nucleotide analogue (decreased IMP) Uses up PRPP => Decreased de novo purine synthesis => decreased AMP/GMP
Methotrexate
Folate analogue => irreversible binds dihydrofolate reductase => unable to regenerate THF Usage: childhood leukemia, psoriasis. Also kills rapidly dividing cells like bone marrow, intestine, hair?
5-Fluorodeoxyuridine (suicide inhibitor)
thymidine kinase converts to nucleotide fdUMP (similar to AZT=>AZT triphosphates) fdUMP = dUMP analogue = binds/inhibits thymidylate synthetase => inhibited production of dTMP
