Folate biosynthesis is a pathway by which pterin and pABA precursors form tetrahydrofolate, an essential cofactor that takes part in various enzymatic reactions as a carrier for one-carbon units. Although tetrahydrofolate is synthesized in the mitochondrial matrix, the pterin and pABA branches occur in the cytosol and the chloroplast, respectively. The first reaction in the pABA branch is catalyzed by aminodeoxychorismate synthase (ADCS) whereby chorismate and L-glutamine is converted to aminodeoxychorismate and L-glutamic acid. The second reaction in the pABA branch is catalyzed by aminodeoxychorismate lyase (ADCL) whereby aminodeoxychorismate is converted to pABA, pyruvic acid, and a hydrogen ion. pABA then diffuses out of the chloroplast and into the mitochondrial matrix to be used in folate biosynthesis. From the pterin branch, hydroxymethyldihydropterin (HMDHP) is pumped into the mitochondria by a yet to be discovered HMDHP transporter. The bifunctional enzyme hydroxymethyldihydropterin pyrophosphokinase-dihydropteroate synthase (HPPK-DHPS), which requires magnesium as a cofactor, catalyzes consecutive steps that unites the pABA and pterin branches. 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. Next, dihydrofolate (DHF) synthase catalyzes the ATP hydrolysis powered conversion of dihydropteroate and L-glutamic acid to dihydrofolate. Finally, the DHFR domain of the bifunctional enzyme dihydrofolate reductase-thymidylate synthase (DHFR-TS) reduces dihydrofolate to tetrahydrofolate with the help of NADPH and a hydrogen ion.

Folate Biosynthesis References