Answer to Question #292081 in Biochemistry for Aadhavan

Question

Why uracil concentration increases in ornithine transcorbamylase deficiency?

Answer 1

Ornithine transcarbamylase (OTC) deficiency is the most common urea cycle defect. The enzyme catalyzes the condensation of carbamyl phosphate and ornithine to form citrulline. Deficiency of OTC  results in accumulation of carbamyl phosphate, which enters the cytoplasm and is available for de novo pyrimidine biosynthesis. As a result, orotic acid and uracil will be elevated and excreted into the urine. OTCD results in accumulation of carbamoyl phosphate in the mitochondria, which then leaks into the cytoplasm to be used as a substrate for pyrimidine biosynthesis resulting in increase in uracil. 

 Increased uracil is characteristic of enzyme deficiencies of pyrimidine metabolism. Uracil can accumulate in UCDs, due to shunting of carbamoylphosphate to pyrimidine synthesis