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
Methanogenesis or biomethanation is the formation of methane coupled to energy conservation by microbes known as methanogens. Organisms capable of producing methane for energy conservation have been identified only from the domain Archaea, a group ...
. It is the carrier of the C1 group as it is reduced to the
methyl
In organic chemistry, a methyl group is an alkyl derived from methane, containing one carbon atom bonded to three hydrogen atoms, having chemical formula . In formulas, the group is often abbreviated as Me. This hydrocarbon group occurs in many ...
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 bacteria. ...
.
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
In organic chemistry, a methyl group is an alkyl derived from methane, containing one carbon atom bonded to three hydrogen atoms, having chemical formula . In formulas, the group is often abbreviated as Me. This hydrocarbon group occurs in many ...
donor to
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 bacteria. ...
, 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