Nitrogen Metabolism

Question 1

What substrates are affected by hartnup disease

Answer 1

Neutral amino acids

[defective transporter]

Question 2

Common treatment for hartnup

Answer 2

Supplement with niacin or nicotinic acid (B3) to increase production of NAD or NADP (bc Trp is a precursor to those)

Question 3

Individual substrates affected in Cystinuria

Answer 3

COAL - dibasic amino acids

Cystine, ornithine, arginine, lysine

Question 4

Major clinical manifestation of cystinuria

Answer 4

Cystine nephrolithiasis

Question 5

Of the individual substrates affected in Cystinuria, ______ is a non-protein amino acid which is a substrate in the urea cycle

Answer 5

Ornithine

Question 6

Why are cystinuria and hartnup considered double-whammy diseases

Answer 6

Malabsorption in intestinal lumen AND decreased reabsorption from filtrate (bc defective transporters in intestine and kidney!)

Question 7

Rate limiting step of urea cycle

Answer 7

Conversion of ammonia to carbamoyl phosphate by CPSase I and NAG activation

Question 8

What is the carbon skeleton for urea cycle transamination reactions?

Answer 8

Aspartate

Question 9

What is the first step of nitrogen removal from the body?

Answer 9

Oxidative deamination by glutamate dehydrogenase

Question 10

What enzyme is affected in PKU

Answer 10

Phenylalanine hydroxylase

Question 11

Difference between classic and non-classic PKU

Answer 11

Classic = deficiency in PAH

Non-classic = THB deficiency, a necessary cofactor for PAH

[note that THB is also necessary for NO production from Arg, it is regenerated from NADPH-dependent reduction of BH2]

Question 12

What IEM results in musty urine odor and is the most common IEM?

Answer 12

PKU

Question 13

PKU is treated dietarily and with supplementation of ____. metabolic control improves with treatment with _____

Answer 13

Tyr

THB

Question 14

Which type of tyrosinemia is most common, what are the symptoms

Answer 14

Type 1 - cabbage smelling urine, severe liver failure (need transplant), inhibition of heme biosynthesis

Question 15

What type of tyrosinemia is a defective tyrosine aminotransferase and presents as photophobia and skin lesions on palms+soles?

Answer 15

Type II

Question 16

What type of tyrosinemia is characterized by intermittent ataxia?

Answer 16

Type III

Question 17

What enzyme is affected by alkaptonuria and what is the characteristic triad of this disease?

Answer 17

Homogentisate oxidase (involved in tyr degradation)

Homogentisic aciduria + ochronosis + arthritis

Question 18

Difference between primary and secondary hyperuricemia (gout)

Answer 18

Primary = overproduction of uric acid

Secondary = underexcretion of uric acid (most cases)

Question 19

Diagnostic marker and treatment options for gout

Answer 19

Diagnostic marker = uric acid levels in blood

Allopurinol = inhibits xanthine oxidase, increasing levels of more soluble purines in the blood like hypoxanthine and guanine

Colchicine = decreases movement of granulocytes to the area

Question 20

Varying presentations of hyperammonemia

Answer 20

Orotic aciduria
Citrullinemia
Argininosuccinate aciduria

Question 21

X-linked form of hyperammonemia

Answer 21

Defective ornithine transcarbamoylase - causes excess carbamoyl phosphate which can spill into cytoplasm and get metabolized by pyrimidine synthesis pathway to orotic acid which accumulates –> orotic aciduria

(Often accompanied by decreased BUN)

Question 22

Compare CPSase I with CPSase II

Answer 22

CPSase I = urea cycle, mitochondrial, NAG-activated

CPSase II = pyrimidine synthesis, cytosolic, PRPP activated

Question 23

Difference between direct and indirect bili

Answer 23

Direct = conjugated to glucuronate, soluble, reacts with Diazo

Indirect = unconjugated, insoluble, made soluble by methanol

Question 24

How would you measure indirect bili in a serum sample

Answer 24

React with diazo + methanol to get total bili

React with diazo ONLY to get direct bili

Difference between these = indirect