Orotic

Orotic refers to orotic acid and its salts, collectively called orotate. Orotic acid is an organic carboxylic acid that serves as a key intermediate in the de novo synthesis of pyrimidine nucleotides. The term also covers the salts and esters of orotate, which appear in biological systems and in laboratory contexts as reagents and substrates for nucleotide synthesis studies.

Biochemical role: In the pyrimidine biosynthesis pathway, orotate is formed from carbamoyl phosphate and aspartate through a series of enzymatic steps. It is then activated by orotate phosphoribosyltransferase (and, in many organisms, a bifunctional enzyme that also contains orotidine-5'-phosphate decarboxylase) to form uridine monophosphate (UMP), which is subsequently converted to other pyrimidine nucleotides. Orotate metabolism thus links basic carbon and nitrogen metabolism to nucleotide production.

Clinical and diagnostic aspects: Orotic aciduria is a rare inherited metabolic disorder caused by deficiency of the UMPS enzyme, leading to accumulation of orotate and excretion in urine, along with megaloblastic anemia, growth retardation, and developmental delay. Urinary orotic acid is a diagnostic marker. Treatment typically involves supplementation with uridine or uridine monophosphate to bypass the metabolic block and restore pyrimidine nucleotide synthesis.