BIOCHEMISTRY - Textbook - Ostapchenko L. I. - 2012

Chapter 10. NUCLEIC ACID METABOLISM

10.3. Catabolism of Pyrimidine Bases

The breakdown of pyrimidine bases (uracil, cytosine, thymine) begins with the reduction of the pyrimidine ring, which is subsequently cleaved hydrolytically. In The First stage, the degradation of cytosine and methylcytosine is accompanied by deamination, leading to The formation of uracil and thymine, respectively (Fig. 10.4). This conversion occurs via hydrolytic deamination. Next, in the presence of dihydropyrimidine dehydrogenases and NADPH, thymine and uracil add two hydrogen atoms across the double bond of the ring to form dihydrothymine and dihydrouracil. Both heterocycles react with Water in a reaction catalyzed by dihydropyrimidine cyclohydrolase, converting dihydrothymine into β-ureidoisobutyric acid and dihydrouracil into β-ureidopropionic acid. Subsequently, the pyrimidine ring of the thymine and uracil dihydro derivatives is opened by the action of ureidopropionase, an enzyme common to both, yielding CO2, NH3, and β-aminoisobutyric acid or β-Alanine, respectively.

Ammonia and carbon dioxide resulting from the degradation of thymine and uracil are utilized for the synthesis of urea, which is excreted in the urine. The β-aminoisobutyrate and a portion of the β-alanine undergo Transamination with α-ketoglutarate to yield methylmalonyl semialdehyde or malonyl semialdehyde, respectively, which are then converted into succinyl-CoA and malonyl-CoA to be used in corresponding metabolic pathways or oxidized to CO₂ and Н₂О.

Most of the β-alanine remains in a free state, present in many Tissues and Blood Plasma, or is utilized in Muscles for the Synthesis of the dipeptides Carnosine and Anserine. Bacterial Cells use β-alanine for the synthesis of pantothenic acid, which is a component of HS-CoA.