Nitrogen Metabolism Flashcards
first step of nitrogen removal and enzyme involved
oxidative deamination via glutamate dehydrogenase
key player in AA metabolism
glutamate
source of carbon skeletons for urea cycle generated from transamination reactions
aspartate
nitrogen sources for the urea cycle
Glu/Gln
inborn errors of AA resorption (2)
hartnup - nonpolar AA
Cystinuria - dibasic AA
AA are resorbed in which portion of the nephron
proximal convoluted tubule
cystinuria is characterized by defective ________ enzyme in what tissue
shared dibasic-cystine transporter in the proximal renal tubule and JEJUNAL MUCOSA
what picks up the slack for the shared dibasic-cystine transporter in the small intestines?
a peptide transporter
hartnup is characterized by a defective ________ enzyme in what tissue
neutral AA transporter in the proximal renal tubule and jejunal mucosa
most important AA that is ineffectively resorbed in the PCT in patients with hartnup is
tryptophan, precursor for neurotransmitters
dibasic AA
COAL Cystine Ornithine Argnine Lysine
neutral AA transporter deficiency
Ala, Ser, Thr, Val, Leu, Ile, Phe, Tyr, Trp, Gln, Asn
hartnup disease
Trp is the precursor for what molecules
serotonin
melatonin
niacin (which is a precursor for NAD) - note niacin deficiency
manifestations of Hartnup disease
failure to thrive, nystagmus, intermittent ataxia, tremor and photosensitivity
pellagra like dermatosis
attacks triggered by sunlight, drugs, physical stress
treatment for hartnup
nicotinic acid
niacin repletion and high protein diet, daily nicotinamide supplementation
nitroprusside test indicates
cystinuria
cystinuria can dissolve kidney stones by changing their diet to be more
alkalinic
phenylketonuria is caused by deficient
Phenylalanine hydroxylase (PAH) most common IEM
PKU symptoms can be limited by
dietary limitation of Phe and supplementation of Tyr
secondary PKU is characterized by
Tetrahydrobiopterin deficiency
THB is a key coenzyme in phenylalanine hydroxylase
defect in synthesis/regeneration of B4
PKU babies must be treated before _____ of age
Dietary restrictions begin if blood Phe levels are greater than _____
some patients with milder forms can increase their metabolic control with supplementation with _______
2 weeks of age
6mg/dL
improved metabolic control when treated with THB
Tetrahydriobiopterin is a cofactor for what enzyme
phenylalanine hydroxylase
synthetic THB treats what IEM
secondary PKU
tyrosinemias are characterized by
elevated blood levels of tyrosine
deficient fumarylacetoacetate hydrolase results in what form of tyrosinemia and what does the enzyme do
Type I
converts tyrosime to fumarate
type I tyrosinemia is characterized by deficient
fumarylacetoacetate hydrolase
Type I tyrosinemia babies have a _____ like smell and excrete ______, which is toxic to liver and kidneys, interferes with the TCA cycle, causes renal tubule dysfunction and inhibits biosynthesis of heme
cabbage
secrete succinylacetone
type II tyrosinemia is characterized by
defective tyrosine aminotransferase
results in photophobia/skin lesions
type III tyrosinemia is characterized by
defective p-hydroxyphenylpyruvate oxidase and results in intermittent ataxia
what type of tyrosinemia is most common and used to require a liver transplant?
type I
deficient fumarylacetoacetate hydrolase
buildup of succinylacetone
defective homogentisate oxidase, an enzyme in tyrosine degradation pathway, results in black urine and bones is termed
alkaptonuria
a buildup of homogentistic acid is due to what enzyme in alkaptonuria
homogentisate oxidase
NH3 toxicity MoA
permeates membranes
pH imbalance, swelling of astrocytes in the brain –> cerebral edema/intracranial hypertension
enzyme that catalyzes the oxidative deamination of glutamate to alpha-ketoglutarate
glutamate dehydrogenase
ammonia depletes what NT
glutamate
gout is a buildup of
uric acid in the blood and deposition of sodium urate crystals
primary hyperuricemia –> overproduction of uric acid
Secondary hyperuricemia –> underexcretion of uric acid
diets rich in ________ along with what other foods/drinks trigger gout
purines
alcohol, meat, seafood
treatments of gout
colchicine decreases the movement of granulocytes to the affected areas
use of allopurinol inhibits xanthine oxidase
hyperammonemia is caused by defects in what enzymes
six enzymes of the urea cycle or 3 specific transporters
mitochondrial ornithine carriers, mitochondrial Asp/Glu carrier, dibasic AA transporter
more severe cases of hyperammonemia are due to defects in what enzymes
3 specific transporters
mitochondrial ornithine carriers, mitochondrial Asp/Glu carrier, dibasic AA transporter
ornithine transcarbamoylase deficiency results in what condition
hyperammonemia
defects cause excess carbamoyl phosphate which can spill out into cytoplasm
metabolized by pyrimidine synthesis pathway to orotic acid then accumulates/excreted in the urine (orotic aciduria) –> decreases BUN
first step of de novo pyrimidine synthesis is mediated by what enzyme
carbamoyl phosphate synthetase II - cytosol
unique from mitochondrial isoform
carbamoyl phosphate synthetase I
urea cycle
mitochondrial
NAG activated
Carbomyl phosphate synthetase II
pyrimidine synthesis
cytosolic
PRPP activated
Carbamoyl phosphate synthetase I is the rate limiting step for what process
urea cycle
deficiency == hyperammonemia
creates carbamoyl phosphate which is used added to ornithine to make citrulline (allows urea to exit the mitochondria)
bilirubin is conjugated with
glucuronic acid
by UDP glucuronyl transferase
unconjugated bilirubin is trasnported to the liver from the spleen using
albumin?
heme is broken down to bilirubin in the
macrophage
unconjugated bilirubin is water ______ while conjugated bilirubin is water _______
insoluble
soluble
jaundice is common in newborns because
placenta handles removal of bilirubin, after birth babies liver must take over the job
