Amino Acid Catabolism Overview

Study Notes

Amino acid catabolism is the process of breaking down amino acids.
Nitrogen enters the body through dietary protein.
Nitrogen leaves the body as urea, ammonia, and other products derived from amino acids.
The amino acid pool refers to the total amount of free amino acids in the body.
Protein turnover is the continuous breakdown and synthesis of proteins.

Ammonia Formation:
- All amino acids are first transaminated to glutamate.
- Glutamate is then deaminated, forming ammonia.
Ammonia Trapping:
- Ammonia is highly toxic, especially to the central nervous system.
- Intracellular ammonia is trapped by glutamic acid to form glutamine.
- Glutamine is non-toxic and can be transported to the liver via the bloodstream.
Final Disposal of Ammonia:
- Glutamine is cleaved by glutaminase in the liver, releasing ammonia and glutamic acid.
- Ammonia is detoxified in the liver by conversion to urea.
- Urea is excreted in the urine.

Formation of Carbamoyl Phosphate:
- One molecule of ammonia condenses with CO2 in the presence of two molecules of ATP to form carbamoyl phosphate.
- This reaction is catalyzed by carbamoyl phosphate synthetase I (CPS-I).
- CPS-I is the rate-limiting step in urea formation.
Cleavage of Argininosuccinate:
- Argininosuccinate is cleaved to arginine and fumarate by argininosuccinate lyase.
- Fumarate is hydrated to malate, linking the urea cycle to other metabolic pathways.

Urea diffuses from the liver to the kidneys, where it is filtered and excreted in the urine.
Some urea diffuses from the blood to the intestines, where it is cleaved by bacterial urease to CO2 and NH3.
This ammonia is partially lost in feces or reabsorbed into the blood.

Kidney Failure: Plasma urea levels are elevated in patients with kidney failure. Ammonia levels also increase due to the action of intestinal bacterial urease.
Hepatic Encephalopathy: Patients with hepatic encephalopathy may benefit from lactulose, which decreases intestinal ammonia production and absorption.
Antibiotics: Neomycin can be administered orally to patients with kidney failure to reduce the number of intestinal bacteria and decrease ammonia production.