BIOCHEMISTRY: A TEXTBOOK FOR UNIVERSITIES - E. S. Severin - 2004

SECTION 10. NUCLEOTIDE METABOLISM

VI. Catabolism of pyrimidine nucleotides

As previously mentioned, cytidylyl NUCLEOTIDES can undergo hydrolytic deamination to form UMP. When inorganic phosphate and ribose are cleaved from UMP through the action of a nucleotidase (or phosphatase) and uridine phosphorylase, the remaining product is the nitrogenous base uracil. Deoxynucleotides are degraded in a similar manner: dCMP yields uracil, whereas dTMP yields thymine (Fig. 10-16).

Class="center">Fig. 10-16. Catabolism of pyrimidine bases. 1 — dihydropyrimidine dehydrogenase; 2 — dihydropyrimidinase (dihydropyrimidine cyclohydrolase); 3 — ureidopropionase.

In the presence of dihydropyrimidine dehydrogenase, pyrimidine bases add two hydrogen atoms across the double bond of the ring to form dihydrouracil or dihydrothymine. Both heterocycles can react with Water in a reaction catalyzed by dihydropyrimidinase (dihydropyrimidine cyclohydrolase), converting dihydrouracil to β-ureidopropionic acid and dihydrothymine to β-ureidoisobutyric acid. Both β-ureido derivatives are cleaved by a shared enzyme, ureidopropionase, to yield CO₂, NH₄⁺, and either β-Alanine or β-aminoisobutyric acid, respectively.

β-Alanine is found in Blood Plasma and numerous Tissues. In Muscle, it is utilized for the Synthesis of the dipeptides Carnosine and Anserine. Under the action of the intestinal bacterial microflora, β-alanine is incorporated into pantothenic acid, which is absorbed and utilized for CoA Biosynthesis.

Part of the β-alanine and β-aminobutyrate undergoes Transamination with α-ketoglutarate to yield malonate semialdehyde or methylmalonate semialdehyde, respectively. These intermediates are subsequently converted to malonyl-CoA and succinyl-CoA for use in corresponding metabolic pathways, or they are oxidized to CO₂ and Н₂О. A fraction of β-aminobutyrate is excreted in the urine.