Dihydroorotase (DHO)

Dihydroorotase is a zinc-dependent metalloenzyme that catalyzes the reversible interconversion of carbamoyl aspartate and dihydroorotate, an essential step in the de novo biosynthesis of pyrimidine nucleotides[1][2][3][4][5][6][7]. This enzyme is highly conserved across bacteria, yeast, and multicellular eukaryotes. In many organisms, including humans, the dihydroorotase activity is part of a multifunctional protein complex (CAD protein), which combines the first three steps in pyrimidine biosynthesis[7]. Structurally, dihydroorotase uses a binuclear zinc active site to activate water and mediate amide bond hydrolysis[2][3][4][5]. The enzyme plays a critical role in cellular nucleotide metabolism and is regulated by allosteric feedback from downstream nucleotides such as UTP and UMP[7]. Dihydroorotase has been investigated as a potential drug target in anticancer and antimicrobial drug development due to its central role in nucleotide synthesis and the differences observed between human and microbial enzymes[6].

Other names

DHODihydroorotate amidohydrolaseDihydroorotate hydrolaseOrotic acid hydrolase

Inhibition of Dihydroorotase blocks pyrimidine nucleotide biosynthesis, leading to antiproliferative effects, particularly in rapidly dividing cells such as cancer or pathogens