L26: Nitrogen Excretion

Question 1

LO1: Name the four major end points of nitrogen metabolism and describe the pathways that give rise to these compounds

Answer 1

1. Urea, from urea cycle (86%)
2. Creatinine, from creatine (4.5%)
3. Ammonium ion, breakdown of glutamine (2.8%)
4. Uric acid, purine metabolism (1.7%)

Question 2

LO2: Describe the two enzymatic reactions required for renal ammoniagenesis

Answer 2

1. glutaminase removes the amide roup of the side chain of glutamine
2. glutamate dehydrogenase removes the alpha-amino group of glutamate

Question 3

LO3: Relate ammoniagenesis to acidosis and proton excretion, and predict two abnormalities of metabolism that would result in increased ammoniagenesis

Answer 3

• excretion of protons requires a buffer to reduce urine volume and maintain functional proton gradient
• ammoniagenesis increases during acidosis so that chloride is excreted instead of Na+/K+ to preserve them

-metabolic abnormalities that cause acidosis will increase ammoniagenesis, as will ketoacidosis

Question 4

LO4: Explain how increases in renal ammoniagenesis can result in increased renal gluconeogenesis

Answer 4

• when kidney creates alpha-ketoglutarate from glutamine, NH3 and NADH are also formed
• NADH is part of the TCA cycle and is a substrate for gluconeogenesis and will increase the reaction

Question 5

LO5: Compare and contrast the reactions that give rise to creatine and creatINine

Answer 5

CREATINE
arginine+glycine+SAM—->creatine
-enzyme mediated

CREATININE
creatinine—–spontaneous cyclization or creatine phosphate—>creatinine

Question 6

LO6: Name the end product of purine catabolism and describe the general strategy used by mammalian cells to degrade purines

Answer 6

-humans can’t open up the purine ring system to degrade it, so its substituents are removed and the ring’s carbon atoms are oxidized to make the ring soluble

Purine (A/G)—loss of P—>nucleoside—-loss of sugar—>purine base—->xanthine—>uric acid (via xanthine oxidase)

-purines can also be recycled by condensation with PRPP (catalyzed by HGPRT), but some uric acid is produced due to inefficiency of recycling

Question 7

LO7: Name three enzyme defects that result in overproduction of uric acid

Answer 7

too much uric acid=gout

1. deficiency in HGPRT, including Lesch-Nyhan syndrome
2. excessive activity of PRPP synthethase
3. Glucose-6-phosphatase deficiency (due to excess production of purines and impaired uric acid excretion)

Question 8

LO8: Provide a biochemical rationale for the use of allopurinol to treat gout

Answer 8

• allopurinol=hypoxanthine analog
• rapidly converted to oxypurinol, which inhibits xanthine oxidase
• uric acid synthesis is lowered and xanthine/hypoxanthine levels are increased (more soluble than uric acid and are less likely to form crystals/trigger immune response)
• hypoxanthine can then enter the recycling pathway