File:Transport of folate compounds from the intestine to the brain and competitive inhibition of 5-MTHF transport by folic acid.png

English: Transport of folate compounds from the intestine to the brain and competitive inhibition of 5MTHF transport by FA. Conversion of FA to 5MTHF is limited in the intestine and is mainly handled by DHFR in the liver, although its enzymatic activity is low in humans. In contrast, folinic acid is efficiently metabolized to 5MTHF in the intestine and liver. When an excess amount of FA is taken, it cannot be fully reduced by DHFR in the liver and unmetabolized FA appears in the plasma. Because FA has higher affinity to FR1 expressed at the choroid plexus than 5MTHF, it can act as a competitive inhibitor against 5MTHF transport from the plasma to the CSF. In addition, FA cannot be metabolized to 5MTHF efficiently in the brain with extremely low DHFR activity. Thus, excess FA intake may lead to a less effective supply of 5MTHF to the brain compared with that of folinic acid supplementation. Dashed arrows indicate more than one-step enzymatic reactions. 5MTHF, 5-methyltetrahydrofolic acid; CSF, cerebrospinal fluid; DHFR, dihydrofolate reductase; FA, folic acid; FR1, folate receptor 1; MTHFR, methylenetetrahydrofolate reductase; THF, tetrahydrofolate