8. Nitrogen Metabolism

Question 1

What is the key enzyme and the rate limiting step to take out nitrogen from urea?

Answer 1

carbamoyl phosphate synthase I (CPSI) (converts ammonia to carbamoyl phosphate)

Question 2

What are the 3 mains sources of nitrogen and where do they come from?

Answer 2

glutamate from the liver
glutamine from outside the liver
Alanine from muscle

Question 3

What is the first step of nitrogen removal?

Answer 3

oxidative deamination

Question 4

Glomerular filtration is the process by which the kidneys filter the blood removing excess wastes and fluids. What is associated with hartnups disease and cystinuria?

Answer 4

hartnups is a defect in reabsorption of nonpolar AA
cystinuria is a defect in the reabsorption of dibasic AA
this can occur in both the small intestine and kidney

Question 5

Where does rabsorption of AA and glucose occur?

Answer 5

in the proximal convoluted tubule (PCT)

Question 6

hartnups diesase is characterized by a defective transport of neutral/nonpolar AAs. What is the most common one?

Answer 6

tryptophan

Question 7

Cystinuria is the defective transport of dibasic aminos acids such as?

Answer 7

cystine, lysine, agrinine and ornithine

Question 8

Hartnups is an AR disorder, affecting TRP*, Ala, ser, thr, val, leu, ile, phe, tyr, gln, and asn. Trp is a precursor for serotonin, melatonin and _____ which is a precursor for NAD.

Answer 8

NIACIN

Question 9

What are some presentations of Hartnups and what is the common treatment plan?

Answer 9

presents with failure to thrive, eye movement, photosensistivity triggered by sunlight (period of poor nutrition)
commonly treated withniacin repletion an high protein diet

Question 10

What is niacin (made from Trp) a coenzyme for?

Answer 10

NAD/NADP

Question 11

What is the most common treatment for hartnups disease?

Answer 11

supplementing with niacin (nicaotinic acid/VitB3)

Question 12

Cystinuria is the defect in the uptake system of dibasic/dimeric amino acid cystine, along with Arg Lyz and ornithine (COAL) which is AR. What does it result in and what forms?

Answer 12

results in partient presenting with renal colic and cystine crystals forming in the kidneys (+nitroprusside test)

Question 13

Phenylketonuria (PKU), the classic form is caused by a deficiency in phenylalanine hydroxylase (PAH). While secondary non-classical PKU is caused by a deficiency/defect in?

Answer 13

tertahydrobiopterin (THB) which is the cofactor to make phenyalanine into tyrosine

Question 14

Phenylketonuria can be tested via guthrie test and will have a musty odor in the urine due to phenylacetate. What is the most concerning problem with this?

Answer 14

leads to brain damage

can avoid symptoms by limiting Phe consumption in diet

Question 15

So neurological affects of PKU do not occur, the babe should be tested before the child is 2 weeks, and the levels should not be greater than 360umol/L. Some mild forms are treated with?

Answer 15

THB 5-20mg per day

Question 16

There are three types of tyrosinemias, type 1 2 and 3. What does a tyrosinemia mean?

Answer 16

elevated blood levels of tyrosine

Question 17

Tyrosinemia type 1 (most common) occurs due to a deficiency in fumarylacetoacetate hydrolase which converts fumarylacetoacetate into? what side effects are seen?

Answer 17

fumarate

severe liver failure

Question 18

Tyrosinemia type II occurs due to a defect in tyrosine aminotransferease which converts Tyrosine into? what side effects are seen?

Answer 18

glutamate and p-hydroxyphenylpyruvate

photophobia and skin lesions on palms

Question 19

Tyrosinemia type III occurs due to defect p-hydroxyphenylpyruvate oxidase which coverts p-hydroxyphenylpyruvate into? what side effects are seen?

Answer 19

homogentisate

intermitent ataxia

Question 20

Alkaptonuria is due to defective homogentisate oxidase which is an enzyme involved in converting homogentisate into? what side effects are seen?

Answer 20

maleylacetoacetate

black urine, black spots on eyes, black skin lesions

Question 21

Gout is characterized as high levels of uric acid in the blood. primary is overproduction and secondary hyperuricemia is under excretion of uric acid. Diets rich in what can trigger this? (4)

Answer 21

purines such as beans spinach lentils
alcohol
meats
seafood

Question 22

What is the main treatment for gout?

Answer 22

allopurinol which inhibits xanthine oxidase so uric acid will not form and accumulate

Question 23

Hyperammonemia can occur with any of the 6 enzymes (such as NAG synthase) or the 3 transporters that are associated with?

Answer 23

the urea cycle

Question 24

Defects in mitochondrial trasnporters results in severe hyperammonemia. Which enzyme is Xlinked recessive?

Answer 24

ornithine transcarbamoylase

Question 25

ornithin transcarbamoylase is xlinked recessive mutation which cause orotic aciduria. It causes what?

Answer 25

excess carbamoyl phosphate, which is processed by the pyrimidine synthesis to orotic acid and accumulates to orotic aciduria and hyperammonemia
(treat w low protein and promoting excretion)

Question 26

carbamoyl phosphate synthetase II, which is different from the mitochondrial isoform that functions in the urea cycle. It is involved in the first step of pyrimidine synthesis which is stimulated by PrPP and inhibited by?

Answer 26

UTP

An AR defect in UMP synthase can lead to accumulation of orotic acid and lead to orotic aciduria, not accompanied with hyperammonemia

Question 27

What are the three characteristics of CPSase I?

Answer 27

in urea cycle
mitochondiral location
NAG-activated

Question 28

What are the three charcteristics of CPSase II?

Answer 28

In pyrimidine synthesis
cytosolic location
PRPP-activated

Question 29

What is the enzyme used to go from unconjugated to conjugated bilirubin?

Answer 29

UDP glucuronyl transferase

Question 30

Why does a baby usually have fetal jaundice?

Answer 30

because the mother conjugates for the baby via fetal placenta and when it is born it has to conjugate with its own liver, so takes time (7-10 days)

Question 31

unconjugated bilirubin is fairly water insoluble while conjugated bilirubin is?

Answer 31

water soluble

Question 32

Normal bilirubin in infants is 1-12mg/dL. severe jaundice may occur if there is an increase need to replace the number of RBCs such as sickle cell anemia, hemolysis, and what other problems?

Answer 32

cephalohematoma, high levels of RBCs, infection, premature birth, and hemolytic anemias