Cyclohydrolases

Cyclohydrolases are enzymes that catalyze hydrolytic reactions involving cyclic substrates, typically converting a cyclic molecule into a product with a different ring structure or a linear form. They participate in the biosynthesis and turnover of several cofactors, pigments, and secondary metabolites. The term encompasses diverse enzymes that share the common theme of ring-opening or ring modification through hydrolysis, rather than simple bond cleavage.

Mechanistically, cyclohydrolases often act by adding water across a ring bond, yielding a linear or rearranged product. They can be metal-dependent hydrolases or rely on acid-base catalysis; their active sites are adapted to the specific cyclic substrates they encounter in metabolism. The exact mechanism varies among families and substrates.

One well-studied example is GTP cyclohydrolase I, which initiates the biosynthesis of tetrahydrobiopterin, a cofactor for several hydroxylases and decarboxylases. GTP cyclohydrolase II also exists and functions in riboflavin (vitamin B2) biosynthesis, converting GTP into a pyrimidine derivative used further in the pathway. Other cyclohydrolases participate in pterin and folate-related metabolisms.

Because cyclohydrolases play roles in essential cofactor biosynthesis and in secondary metabolism, defects or regulation of these enzymes can impact cellular redox balance, neurotransmitter production, and microbial growth. They are of interest in biochemistry, nutrition, and microbiology, as well as in drug discovery targeting bacterial cyclohydrolases.