Amino acid metabolism II. The urea cycle

Figures:

Lehninger-4ed; chapter: 18

Stryer-5ed; chapter: 23

Overview of amino acid catabolism in mammals

Excretory forms of nitrogen

In ureotelic organisms, the NH3 deposited in the mitochondria of

hepatocytes is converted to urea in the urea cycle.

This pathway was discovered by Hans Krebs (citric acid cycle)

and Kurt Henseleit.

Urea production occurs almost exclusively in the liver and

is the fate of most of NH3 channeled there.

Urea → bloodstream → kidneys → urine

Possible sources of ammonia

● Amino acid degradation in every organ, especially in the liver

and muscles

● Ammonia secretion (5-10% of whole N turnover) in kidney tubules

from glutamine (Chinese Restaurant)

● Nucleotide (pyrimidine) degradation

● Intestinal bacteria produce it from amino acids and urea

Ammonia is very toxic → cerebral edema, increased cranial pressure

(depletion of ATP in brain cells?)

Links between the urea cycle and citric acid cycle

The energetic cost of urea synthesis

2NH4+ + HCO3

¯ + 3ATP + H2O →

urea + 2ADP + 4Pi + AMP + 2H+

● requires 4 high-energy phosphate groups

● NADH is produced in the malate dehydrogenase reaction

(urea cycle ↔ citric acid cycle)

● NADH = 2.5 ATP (mitochondrial respiration)

The overall energetic cost of urea synthesis is reduced!

Regulation of the urea cycle