Nitrogen Metabolism Flashcards
What is the first step of nitrogen removal? What enzyme?
Oxidative deamination via glutamate dehyrogenase
What are three ways to get ammonia in the mitochondria?
Glutamate, Glutamine and Alanine
What is the enzyme that converts ammonia to carbamoyl phosphate (the rate limiting step)
carbamoyl phosphate synthetase
Who is the star of nitrogen flow?
glutamate (liver) and supporting is glutamine (other tissue)
What is the general cause of hartnup disease and cystinuria?
inborn error of metabolism of amino acid resorption; deficiency in membrane transporters (intestinal and renal)
Where in the kidneys does the reabsorption of AAs and glucose occur?
the proximal convoluted tubule
What causes hartnup disease? How would you detect it?
defective transport of neutral/nonpolar amino acids (mostly tryptophan) for reabsorption; lab findings of elevated alanine, serine, threonine, valine, leucine, isoleucine, phenylalanine, tyrosine, tryptophan, glutamine, asparagine, and histidine in urine
What causes Cystinuria? How would you detect it?
defective transport of dibasic amino acids (cystine, onithine, arginine, lysine) for reabsorption; cystine crystals in the kidneys identified by a positive nitroprusside test and patients present with abdominal pain (renal colic)
What three things is tryptophan a precursor for?
serotonin, melatonin, and niacin (NAD)
What is the treatment for hartnup disease?
niacin repletion and nicotinamide supplementation
What is phenylketonuria caused by?
defective phenylalanine hydroxylase (PAH) which converts Phe to Tyr
What is secondary PKU caused by?
tetrahydrobiopterin (TBH) deficiency (a cofactor of PAH)
What is tyrosinemia?
elevated blood levels of tyrosine
What is tyrosinemia type 1 and what is it caused by?
defect in fumarylacetoacetate hydrolase, which converts tryosine to fumarate; infants with this develop liver failure
What is tyrosinemia type II caused by?
defective tyrosine aminotransferase which converts tyrosine to p-hydroxyphenylpyruvate
What is tyrosinemia type III caused by?
defective p-hydroxyphenylpyruvate oxidase which converts p-hydroxyphenylpyruvate to homogentisate
What is alkaptonuria? What is it caused by?
black urine disease; due to defective homogentisate oxidase
What is ammonia toxicity?
excessive ammonia due to disorders in the urea cycle or liver failure can cause highly toxic effects on the brain and CNS
What is gout caused by?
overproduction of uric acid (primary) or underexcretion of uric acid (secondary)
What is hyperammonemia caused by?
defects in any of the six enzymes associated with the urea cycle (carbamoyl phosphate synthetase, ornithine transcarboxylase, arginosuccinate synthetase, arginosuccinate lyase, NAG synthase)
What is the role of carbamoyl phosphate synthetase II in pyrimidine metabolism?
Carbamoyl phosphate synthetase II is involved in the first step of de novo pyrimidine synthesis and converts glutamine to carbamoyl phosphate
What is the role of UDP glucuronyl transferase?
it conjugates bilirubin to become more soluble
What is the difference between direct and indirect bilirubin?
direct bilirubin is conjugated while indirect is unconjugated
Why does juandice occur in newborns?
during gestation, the placenta removes bilirubin and so after birth, the baby’s liver must take over. premature babies are more likely to have jaundice because of underdeveloped kidneys; pathologic jaundice due to SC anemia, hemolysis, etc.
