Home > Flashcards > Print Preview
The flashcards below were created by user
on FreezingBlue Flashcards. What would you like to do?
Auto R. No nucleotide excision repair -- of thymidine dimers. Dry skin w/melanoma & other cancers.
Adenosine deaminase deficiency
Can't do adenosine --> inosine for purine breakdown, so adenosine goes back up to AMP --> nucleic acids: inhibits de novo nucleic acid synthesis. Most severe cause of SCID.
DNA bond formation: the enzyme used & energy source
DNA ligase. The 5' end of incoming nucleotide bears the triphosphate.
Disorder of purine metabolism: mad because you can't "climb up the ladder." Absent HGPRT, so can't do hypoxanthine --> IMP or guanine --> GMP. Excess uric acid --> gout, aggression, retardation.
- Can't do homocysteine --> cystathionine (via cystathionine synthase), which eventually gives you cysteine.
- Tall, hunchback man w/osteoporosis (but it's auto recessive inheritance) with lens subluxation, mental retardation, atherosclerosis.
- Defective renal tubular transporters, so lots of cysteine excreted in urine (plus ornithine, lysine, & arginine).
- Cysteine kidney stones; treat by alkalinizing urine.
Maple syrup urine disease
Deficient Alpha-ketoacid dehydrogenase, so no breakdown of branched-chain AA's (Isoleucine, Leucine, Valine = I Love Vermont maple syrup).
Maple syrup-smelling urine, feeding problems/vomit, mental retardation, CNS deficits, death.
- Black urine, CT, & pigmented sclerae; also, arthralgias. Usually asymptomatic until ~age 40!
- Defective tyrosine breakdown, via homogentisic acid oxidase... so more tyrosine --> dopa --> melanin.
- Defective phenylalanine --> tyrosine (done by phenylalanine hydroxylase). Eczema, fair skin, mental & growth retardation, musty body odor, seizures. Not observable right away at birth, but they do testing.
- Tx: dec'd phenylalanine (in NutraSweet).
Ornithine transcarbamoylase deficiency
Can't do carbamoyl P + ornithine --> citrulline. X-linked recessive. Hyperammonemia sx (slurred speech, blurred vision, tremor, somnolence), plus excess carbamoyl P --> orotic acid in blood & urine.
Tyrosine --> dopa --> melanin, so albinism = defective tyrosine transporter or tyrosinase. Can be due to lack of neural crest cell migration. Variable inheritance patterns, but ocular albinism = X-linked recessive.
Urea cycle mnemonic
Ordinarily, careless crappers are also frivolous about urination. (Aspartate = the first A)
- Megaloblastic anemia. Causes of excess carbamoyl P:
- 1) Urea cycle: ornithine transcarbamoylase deficiency: can't do carbamoyl P + ornithine --> citrulline, so excess carbamoyl P --> converted to orotic acid.
- 2.) De novo pyrimidine synthesis: you're supposed to have carbamoyl P --> orotic acid, but then it's supposed to go orotic acid --> OMP --> UMP. Deficiency in orotic acid phosphoribosyltransferase or orotidine 5'-P decarboxylase.
Difference between the 2: only #1 has hyperammonemia.
- Hexosaminidase A deficiency --> accumulation of GM2 ganglioside in lysosomes.
- Confusion, blind/deaf (cherry-red spots on macula), developmental delay, death by age 4-5. Lysosomes have onion-skinning.
Blind/deaf (cherry-red spots on macula), hepatosplenomegaly (unlike Tay-Sachs). Sphingomyelinase deficiency in lysosomes, so sphingomyelinase accumulates. Foam cells w/zebra bodies, progressive neurodegeneration.
The only 2 lysosomal storage diseases that aren't autosomal recessive
Fabry's & Hunter's (both X-linked recessive)
Lots of organ systems: cardiovascular, renal, GI, peripheral neuropathy, eyes (angiokeratomas, corneal dystrophy). Deficient alpha-galactosidase A (think "alpha-males"); ceramide trihexoside accumulates. X-linked recessive inheritance.
- The most common lysosomal storage disease. Bones: aseptic necrosis of femur, bone crises, Gaucher's cells (macrophages look like crumpled tissue paper = get gifts when you break bones). Hepatosplenomegaly, too. Almost all present in adulthood.
- Deficient B- glucocerebrosidase. Accumulate glucocerebroside.
Crabbiness = cerebral, so galactocerebrosidase deficiency (accumulate galactocerebroside). Peripheral neuropathy, optic atrophy, developmental delay, globoid cells.
- Demyelination -- both central & peripheral. Ataxia, dementia, death age 5-10.
- Deficient arylsulfatase A, accumulate cerebroside sulfate.
Both glucose --> sorbitol and galactose --> galctitol... both cause eye probs.
Glucogenic + ketogenic amino acids
PITT: Phe, Isoleucine, Tryptophan, Threonine
Deficient in maple syrup urine disease (can't break down branched-chain AA's: ILV -- isoleucine, leucine, valine)
Airway obstruction, corneal clouding, gargoylism, developmental delay, hepatosplenomegaly. Enzyme deficient: alpha-L-iduronidase. Accumulated substrate: heparan & dermatan sulfate
Mild Hurler's + aggressive behavior & no corneal clouding. Deficiency of iduronate sulfatase. Accumulated heparan & dermatan sulfate.
- Helps to detach RNA polymerase from RNA after transcription ends.
- RNA polymerase 1 = rRNA, 2 = mRNA, 3 = tRNA