BIOL 304 - Amino Acid Catabolism

Essential amino acids

amino acids that cannot be synthesized and must be acquired in the diet

Protein digestion begins in the

stomach, acidic environment denatures proteins

pepsin

primary proteolytic enzyme of the stomach

Free amino acids, dipeptides, and tripeptides are transported into

intestinal cells

Absorbed amino acids are released into the blood by

Na+-amino acid antiporters

Protein turnover

the degradation and resynthesis of proteins

Ubiquitin

a small (76 aa) protein that tags proteins for destruction

attaches by its carboxyl-terminal Gly residue to the ε-amino groups of 1+ Lys residues on the target protein

ubiquitin-activating enzyme (E1)

adenylate ubiquity and transfers it to a sulfhydryl group of a Cys reside of E1

ubiquitin-conjugating enzyme (E2)

transfers ubiquitin to one of its own sulfhydryl groups

ubiquitin-protein ligase (E3)

transfers ubiquitin from E2 to an e-amino group on the target protein

brings E2 and target protein together

degron

a specific sequence of amino acids that indicates a protein should be degraded

important signal for degradation for E3

N-degron

1st way this amino-terminal residue is exposed

exposed after proteolytic cleavage

2nd way this amino-terminal residue is exposed

may be added after protein synthesis

3rd way this amino-terminal residue is exposed

may require other modification

proteasome (26S)

a large, ATP-driven protease complex that digests ubiquitinated proteins

Contain ubiquitin receptors that bind specifically to polyubiquinated chains

1st step of amino acid degradation

removal of nitrogen

2nd step in amino acid degradation

glutamate is oxidatively deaminated in the liver to yield NH4+

aminotransferases

catalyze the transfer of an alpha-amino acid to an alpha-ketoacid

glutamate dehydrogenase

a mitochondrial enzyme that converts the nitrogen atom in glutamate to a free ammonia ion by oxidative deamination

NH4+ is converted into

urea

Carbamoyl phosphate synthetase I

catalyzes the coupling of ammonia with bicarbonate to form carbamoyl phosphate

Carbamoyl phosphate synthetase I requires

N-acetylglutamate

Ornithine transcarbomoylase

catalyzes the transfer of the carbamoyl group of carbamoyl phosphate to ornithine forming citrulline

Argininosuccinate synthetase

catalyzes the condensation of citrulline and aspartate to form argininosuccinate

Argininosuccinase

cleaves argininosuccinate into arginine and fumarate

Arginase

hydrolyzes arginine to generate urea and ornithine