Pterin biosynthesis is a pathway located in the cytosol by which GTP becomes hydroxymethyldihydropterin (HMDHP), the pterin precursor of folate biosynthesis. Firstly, GTP cyclohydrolase (GCH) catalyzes the conversion of GTP and water to dihydroneopterin triphosphate, formic acid, and water. Secondly, nudix hydrolase from the Nudix (NUcleotide DIphosphates linked to some moiety X) protein family of phosphohydrolases uses water to eliminate a pyrophosphate from dihydroneopterin phosphate and releases a hydrogen ion in the process. However, this enzyme is non-specific for this reaction, and therefore the true dihydroneopterin triphosphate diphosphatase may yet to be found. Thirdly, dihydroneopterin phosphate phosphatase (Pase) dephosphorylates dihydroneopterin phosphate to 7,8-dihydroneopterin. This enzyme has not yet been identified in any organism, but it is possible that reaction is carried out by a nonspecific phosphatase. The fourth reaction is catalyzed by the enzyme dihydroneopterin aldolase (DHNA) whereby 7,8-dihydroneopterin is cleaved to form HMDHP and glycolaldehyde is released. The second function of DHNA is epimerizing 7,8-dihydroneopterin to form 7,8-dihydromonapterin. DHNA can also use 7,8-dihydromonapterin as a substrate to form HMDHP. HMDHP has two fates. It can either be pumped into the mitochondria by a yet to be discovered HMDHP transporter for use in folate biosynthesis, or be acted upon by cytosolic hydroxymethyldihydropterin pyrophosphokinase-dihydropteroate synthase (HPPK-DHPS). HPPK-DHPS is a bifunctional enzyme that requires magnesium as a cofactor and catalyzes consecutive steps in the pterin and folate biosynthesis pathways. The HPPK domain uses ATP to diphosphorylate HMDHP to HMDHP pyrophosphate, releasing AMP and a hydrogen ion in the process. The DHPS domain incorporates pABA, diffused out from the chloroplast, to form dihydropteroate and a diphosphate.

Pterin Biosynthesis (Folate Precursor) References