BIOCHEMISTRY - L. Stryer - 1984

VOLUME 2

PART II GENERATION AND STORAGE OF METABOLIC ENERGY

CHAPTER 18. AMINO ACID DEGRADATION AND THE UREA CYCLE

Summary

Excess Amino Acids are utilized as metabolic fuel. The degradation of most excess amino acids begins with the removal of the α-amino group via Transamination with an α-keto acid. Pyridoxal phosphate serves as the coenzyme for all transaminases. Amino groups are transferred to α-ketoglutarate to yield glutamate, which then undergoes Oxidative Deamination catalyzed by Glutamate dehydrogenase, producing NН+4 and α-ketoglutarate. NAD⁺ or NADР⁺ acts as the electron acceptor in this reaction. In terrestrial vertebrates, NН4+ is converted into urea via The Urea Cycle. Urea is formed through the Hydrolysis of Arginine. Subsequent Reactions of the urea cycle synthesize arginine from Ornithine, another product of the hydrolysis reaction. First, ornithine is carbamoylated to citrulline with the participation of carbamoyl phosphate. Citrulline then condenses with aspartate to form argininosuccinate, which is cleaved into arginine and fumarate. The carbon atom and one nitrogen atom of urea derive from carbamoyl phosphate, which is synthesized from СO₂, NH₄⁺, and АТР. The other nitrogen atom of urea originates from aspartate. Four high-energy phosphate bonds are consumed in the synthesis of a single urea molecule.

The carbon atoms of degraded amino acids are converted into Pyruvate, acetyl-CoA, acetoacetate, or intermediates of The Tricarboxylic Acid Cycle. Most amino acids are exclusively glucogenic, one is strictly ketogenic, and several are both Ketogenic and Glucogenic. The breakdown of Alanine, Serine, Cysteine, Glycine, and Threonine yields pyruvate. Asparagine and aspartate are converted into oxaloacetate. α-Ketoglutarate serves as an entry point into the tricarboxylic acid cycle for glutamate and four Other Amino Acids (glutamine, Histidine, Proline, and arginine) that can be converted into glutamate. Succinyl-CoA serves as an entry point for carbon atoms from four additional amino acids (Methionine, isoleucine, threonine, and valine), whose degradation proceeds via methylmalonyl-CoA. The isomerization of methylmalonyl-CoA to succinyl-CoA requires deoxyadenosylcobalamin, a vitamin B₁₂ derivative. Leucine is degraded to acetoacetyl-CoA and acetyl-CoA. The aromatic rings of Tyrosine and phenylalanine are cleaved by the action of oxygenases. Phenylalanine hydroxylase, a monooxygenase, utilizes tetrahydrobiopterin as a reductant. Some carbon atoms of Phenylalanine and Tyrosine are converted into fumarate, whereas others appear in acetoacetate.