and its one-carbon derivatives, collectively termed folates, are essential cofactors for one-carbon transfer reactions in the biosynthesis of certain amino acids, pantothenate, purines, and thymidylate (Hanson et al.
In PAH, PASMCs proliferation maximizes the usage of methionine for protein synthesis which might reduce the methionine level (choline dehydrogenase: CHDH; methylene tetrahydrofolate
dehydrogenase: MTHFD), although methionine is the metabolic production of betaine.
He attributes this inability to having inherited a variant in the DHFR (dihydrofolate reductase) gene that lowers the ability of DHFR to reduce dihydrofolate into tetrahydrofolate
(BH4), which is essential for breaking down histidine, from which histamine is synthesized.
In folate pathway mechanism deoxythymidine monophosphate (dTMP) (dTMP) is produced from deoxyuridine monophosphate (dUMP) by oxidation of tetrahydrofolate
to dihydrofolate catalysed by dihydrofolate reductase (DHFR) (Hyde 2005; Abali et al.
8] Methotrexate is a folic acid antagonist that inhibits dihydrofolate reductase, which reduces folic acid to tetrahydrofolate
, essential in the synthesis of DNA and RNA.
In this type, rapid deterioration in the course of dependence has been linked to genetic factors involving methyl tetrahydrofolate
reductase (MTHF) function, which may be amenable to intervention.
1]) 5G/5G polymorphism, a heterozygous methyl tetrahydrofolate
reductase (MTHFR) polymorphism, and a normal prothrombin 20210A gene structure.
methyl groups) are transferred from folate or, more specifically, its derivative tetrahydrofolate
, to other molecules.
As a potent inhibitor of dihydrofolate reductase, the rate-limiting enzyme in the production of tetrahydrofolate
, it decreases the de novo production of purines and pyrimidines and interferes with DNA synthesis.
One is methionine synthase (MS), by which Hcy react with 5-methyl tetrahydrofolate
(5mTHF) to become Met.
However, some people with sulfite sensitivity find that supplementation with molybdenum (it is in many multi-vitamin formulations), vitamins B-12, B-6, and B-l, and the coenzyme tetrahydrofolate
to be helpful.
Some of these "dark horses" are Wilson disease, X-linked adrenoleukodystrophy, disorders of creatine metabolism, remethylation disorders (for example, methylene tetrahydrofolate
reductase deficiency), familial hypercholesterolemia, and Friedreich ataxia, just to name a few.