Nitrogen Metabolism

Question 1

What is the one x-linked defective urea cycle enzyme?

what does it cause?

Answer 1

ornithine transcarbamoylase (converts ornithine to citruline)
causes orotic aciduria if defective

Question 2

What is the importance of carbamoyl phophate synthetase II?

Answer 2

Unique from the mitochondrial isoform that functions in the urea cycle
involved in the first step of de novo pyrimidine synthesis
cytosolic, and PRPP-activated

Question 3

What is gout?

Answer 3

primary hyperuricemia = overproduction of uric acid
secondary hyperuricemia = underexcretion of uric acid
extremely painful sodium urate deposits in joints
bc of diets rich in purines
Tx: diet chx, colchicine that decreases movement of granulocytes, allopurinol that inhibits xanthine oxidase –> more soluble hypoxanthine and guanine

Question 4

What is the first step of nitrogen removal?

Answer 4

oxidative deamination

Question 5

What is the main shuffler of nitrogen, especially in the liver?

Answer 5

glutamate

Question 6

What is Alkaptonuria

Answer 6

“black urine disease”
defective homogentisate oxidase (can’t do Homogentisate –> maleylacetoacetate)
characteristic triad of homogentisic aciduria, ochronosis, and arthritis

Question 7

What are the urine-derived metabolites associated with heme metabolism?

Answer 7

Conjugated bilirubin is excreted
UDP glucoronyl transferase conjugates bilirubin in the liver
before liver = unconjugated bilirubin
after liver = conjugated

Question 8

What is the main shuffler of nitrogen outside the liver?

Answer 8

glutamine

Question 9

How does ammonia toxicity occur?

Answer 9

from disorders in the urea cycle or liver failure
NH3+ is the toxic agent vs NH4+ due to its ability to permeate membranes
causes pH imbalance, swelling of astrocytes –> cerebral edema and intracranial hypertension
depletion of glutamate –> disruption of is NT activity (key precursor to GABA)

Question 10

What is type III tyrosinemia?

Answer 10

defective p-hydroxyphenylpyruvate oxidase (can’t do p-HPP –> homogentisate)
causes intermittent ataxia

Question 11

Why does jaundice occur in newborns?

Answer 11

during gestation, the placenta removes bilirubin
after birth, baby must start to do it, but just have to get their liver and UDP glucoronyl transferase going to conjugate bilirubin
blue fluorescent light helps conversion of bilirubin

Question 12

What is the difference btw direct and indirect bilirubin?

Answer 12

direct bilirubin = conjugated; water soluble; reacts w/ diazo reagent
unconjugated bilirubin = indirect, water insoluble

Question 13

What is Hartnup disease?

Answer 13

defective transport of neutral amino acids
especially tryptophan, a precursor of serotonin, melatonin, and niacin
niacin deficiency also noted
symptoms = nystagmus, intermittent ataxia, tremor, and pellagra-like dermatitis
Tx: niacin repletion, high-protein diet

Question 14

What is PKU?

Answer 14

defect in phenylalanine hydroxylase (PAH)
can’t metabolize Phenylalanine to Tyrosine –> buildup of phe –> phenylpyruvate –> phenyllactate (musty odor in urine) –> phenylacetate
causes impairment of brain function
Tx: dietary limit Phe and supplement Tyrosine
Tested by Guthrie Test

Question 15

What is the order of breakdown of phenylalanine?

Answer 15

phe –> Tyr –> p-hydroxyphenylpyruvate –> homogentisate –> maleylacetoacetate –> fumarylacetoacetate –> fumarate

Question 16

How does hyperammonemia occur?

Answer 16

defect in any of 6 enzymes in urea cycle or w/ 3 transporters:
mitochondrial ornithine carriers, mitochondrial Asp/Glu carrier, dibasic AA transporter
defects in transporters result in more severe form
Tx: limiting protein consumption and use of agents that can conjugate excessive components and promote excretion

Question 17

What is Cystinuria

Answer 17

defective transporter of dibasic amino acids in renal tubule and small intestines
COAL
cystine, ornithine, arginine, lysine deficiency
results in cystine crystals formed in kidneys ID’d by positive nitroprusside test

Question 18

What is Type I Tyrosinemia?

Answer 18

most common form
defect in fumarylacetoacetate hydrolase (can’t convert Fumarylacetoacetate –> fumarate)
will excrete succinylacetone which is toxic to liver and kidneys, interferes w/ TCA, and inhibits heme synthesis
infant has a cabbage-like smell and will dev severe liver failure w/out treatment
Tx: nitisinone (prevents formation of fumarylacetoacetate)

Question 19

In what disease do you give niacin supplementation?

What vitamin is this?

Answer 19

hartnup dx

Vitamin B3