Tetrahydromethanopterin (THMPT, ) is a

coenzyme A cofactor is a non-protein chemical compound or metallic ion that is required for an enzyme's role as a catalyst (a catalyst is a substance that increases the rate of a chemical reaction). Cofactors can be considered "helper molecules" that ass ...

in methanogenesis. It is the carrier of the C1 group as it is reduced to the methyl level, before transferring to the

coenzyme M Coenzyme M is a coenzyme required for methyl-transfer reactions in the metabolism of archaeal methanogens, and in the metabolism of other substrates in bacteria. It is also a necessary cofactor in the metabolic pathway of alkene-oxidizing bacteri ...

. Tetrahydrosarcinapterin (THSPT, ) is a modified form of THMPT, wherein a

glutamyl Glutamic acid (symbol Glu or E; the ionic form is known as glutamate) is an α-amino acid that is used by almost all living beings in the biosynthesis of proteins. It is a non-essential nutrient for humans, meaning that the human body can synt ...

group linked to the 2-hydroxy

glutaric acid Glutaric acid is the organic compound with the formula C3H6(COOH)2 . Although the related "linear" dicarboxylic acids adipic and succinic acids are water-soluble only to a few percent at room temperature, the water-solubility of glutaric acid is ...

terminus.

THMPT is the main platform for C1 transformations

N-Formyl

methanofuran Methanofurans are a family of chemical compounds found in methanogenic archaea. These species feature a 2-aminomethylfuran linked to phenoxy group. At least three different end groups are recognized: R = tricarboxyheptanoyl (methanofuran), gluta ...

donates the C1 group to the N5 site of the

pterin Pterin is a heterocyclic compound composed of a pteridine ring system, with a "keto group" (a lactam) and an amino group on positions 4 and 2 respectively. It is structurally related to the parent bicyclic heterocycle called pteridine. Pterins, ...

to give the formyl- THMPT. The formyl group subsequently condenses intramolecularly to give methenyl- , which is then reduced to methylene- THMPT. Methylene- MPT is subsequently converted, using coenzyme F₄₂₀ as the electron source, to methyl- THMPT, catalyzed by F₄₂₀-dependent methylene-THMPT reductase. Methyl- THMPT is the methyl donor to

, a conversion mediated by methyl-THMPT:coenzyme M methyltransferase.

Comparison with tetrahydrofolic acid

THMPT is related to the better known

tetrahydrofolic acid Tetrahydrofolic acid (THFA), or tetrahydrofolate, is a folic acid derivative. Metabolism Human synthesis Tetrahydrofolic acid is produced from dihydrofolic acid by dihydrofolate reductase. This reaction is inhibited by methotrexate. It is conv ...

(THFA, ). The most important difference between THMPT and THFA is that THFA has an electron-withdrawing carbonyl group on the phenyl ring. As a consequence, methenyl- THMPT is more difficult to reduce than methenyl- THFA. Reduction is effected by a so-called iron-sulfur cluster free hydrogenase. The cumbersome name distinguishes this hydrogenase from the so-called Fe-only

hydrogenase A hydrogenase is an enzyme that catalyses the reversible oxidation of molecular hydrogen (H2), as shown below: Hydrogen uptake () is coupled to the reduction of electron acceptors such as oxygen, nitrate, sulfate, carbon dioxide (), and fumarat ...

s that do contain Fe-S cluster.

References

{{Enzyme cofactors Coenzymes Pteridines