24.5. Pyrimidine Catabolism
The pyrimidine nucleotides are converted to their respective nucleosides by the action of 5´-Nucleotidase.
Cytidine (nucleoside) is converted to uridine (nucleoside) by the action of Cytidine deaminase.
Ribose is removed from uridine by the enzyme Uridine Phosphorylase to release the free base uracil, and it is removed from thymidine by the action of thymidine phosphorylase to release the free base thymine.
The enzyme dihydrouracil dehydrogenase reduces the bases uracil and thymine to dihydrouracil and dihydrothymine, respectively.
These two compounds are then acted upon by the enzyme. Dihydropyrimidinase to form uridopropionate or uridoisobutyrate.
The enzyme Uridopropionase hydrolytically removes NH4+ and HCO3– from these compounds to form β-alanine (from uracil) and β-aminoisobutyrate (from thymine).
An aminotransferase (Transaminase) converts β-alanine into malonic semialdehyde and converts β-aminoisobutyrate into methylmalonic semialdehyde.
A dehydrogenase complex oxidizes malonic semialdehyde and couples it to coenzyme A to form malonyl-CoA. The malonyl-CoA can enter fatty acid biosynthesis or more likely it is decarboxylated by malonyl-CoA decarboxylase to acetyl-CoA. and the acetyl-CoA oxidized for energy (ATP).
The same or a similar dehydrogenase complex oxidizes methylmalonic semialdehyde and couples it to CoA forming D-methylmalonyl-CoA. D-methylmalonyl-CoA is an intermediate in the metabolism of odd chain length fatty acids and the amino acids, Met, Val, Thr, and Ile. D-methylmalonyl-CoA is ultimately converted to succinyl-CoA as described previously.
After the base is phosphorylytically released from the deoxyribose by nucleoside Phosphorylase or thymidine phosphorylase the phosphate is moved from C-1 to C-5 by phosphopentose mutase to form deoxyribose-5-phosphate. The deoxyribose-5-phosphate is cleaved to ethanal and glyceraldehyde-3-phosphate by 2-deoxyribose-5-phosphate Aldolase. Carbon 1 & 2 becomes the ethanal and 3, 4, &5 become glyceraldehyde-3-phosphate. The glyceraldehyde-3-phosphate enters glycolysis or gluconeogenesis depending upon the tissue and blood glucose levels. Ethanal is oxidized to acetate by aldehyde dehydrogenase and then the acetate is coupled to Coenzyme A by Acetyl-CoA Synthetase. Acetyl-CoA enters any of the pathways that utilizes Acetyl-CoA, most likely the TCA cycle.