Biochem Flashcards
Fabry’s disease
lysosomal storage disease
a-galactosidase A def->ceramide trihexoside
peripheral neuropathy, cardiovascular/renal disease
angiokeratomas on butt
Gaucher’s disease
lysosomal storage glucocerebrosidase def->glucocerebroside most common hepatosplenomegally, aseptic necrosis, anemia, thrombocytopenia Gaucher's cells (macrophages)
Niemann-Pick disease
lysosomal storage
phingomyelinase->sphingomyelin
progressive neurodegeneration, cherry red spot on macular foam cells
thrombocytopenia and worsening cognitive decline
Tay-Sachs
lysosomal
hexosaminidase A->GM2 ganglioside
progressice neurodegeneration, cheey red spot on macula, lysosomes with onion skin,
no hepatosplenomegaly
Krabbe’s disease
lysosomal
galactocerebrosidase->galactocerebroside
peripheral neuropathy, optic atrophy
affects myelin sheaths and occurs in very young
Metachromatic leukodystrophy
lysosomal
arylsulfatase A->cerebroside sulfate
central and peripheral demyelination with ataxia and dementia
Hurler’s syndrome
lysosomal
a-L-iduronidase->heparin sulfate, dermatan sulfate
gargoylism, corneal clouding
resembles dwarfism
Hunter’s syndrome
lysosomal
iduronate sulfatase->heparan sulfate, dermatan sulfate
mild Hurler’s and aggressive behavior, no corneal clouding
Von Gierkes (type I)
glycogen storage
glucose-6-phosphatase
severe fasting hypoglycemia, increased glycogen in liver and increased blood lactate
Pompe’s (type II)
glycogen
lysosomal a-1,4-glucosidase
cardiomegaly (Pompe’s trashes the pump)
Cori’s (type III)
glycogen debranching enzyme (a-1,6-glucosidase) milder form of type I with normal blood lactate
McArdle’s (type IV)
glycogen
skeletal muscle glycogen phosphorylase
increased glycogen in muscle, painful muscle cramps
5 substances needed to make a purine
glycine, aspartate, glutamine (GAG AAs)
tetrahydrofolate, CO2
purines are Pure As Gold (A, G)
4 substances needed to make a pyrimidine
aspartate, glutamate, CO2 and ATP (last 3 from carbamoyl phosphate)
CUT the PY
what is the rate limiting step in purine synthesis
carbamoyl phophate synthetase II
what is the rate limiting step in pyrimidine synthesis
glutamine PRPP amidotransferase
what are the carbon sources in purine and pyrimidine synthesis
purine: glycine, tetrahydrofolate, CO2
pyrimidine: aspartate and CO2
inhibits ribonucleotide reductase in purine synthesis
hydroxyurea
inhibits dihydrofolate reductase in purine synthesis
methotrexate and trimethoprim
inhibits thymidylate synthase in purine synthesis
5-fluorouracil
inhibits inosine monophosphate dehydrogenase in pyrimidine syntheses if guanine
mycophenolate
inhibits PRPP amidotransferase in pyrimidine synthesis
6-mercaptopurine
characteristic findings in orotic aciduria
inability to convert orotic acid to UMP
increase orotic acid in urine
no increase in ammonia (no hyperammonemia)
failure to thrive
megaloblastic anemia that cannot be corrected with B12 or folate
Tx: oral uridine administration
a boy with self mutilating behavior, intellectual disability and gout
Lesch-Nyhan syndrome
deficiency in HGPRT that increases uric acid
TX: allopurinol