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Pathway · 1 proteins

Folate-linked carbon transfer

One-carbon units support multiple biosynthetic reactions.

How it works

  1. The glycine cleavage system is annotated in full: GcvPA and GcvPB form the aminomethyl-transferring dehydrogenase, GcvT is the aminomethyltransferase, and GcvH is the lipoate-bearing carrier that hands the methylamine between them.
  2. The reaction releases CO2 and ammonia and transfers a methylene unit to tetrahydrofolate, so glycine cleavage is simultaneously a catabolic step and a one-carbon source.
  3. FolD and methylenetetrahydrofolate reductase then distribute those units between biosynthesis and methyl transfer. This is why the module sits inside central carbon: it is the junction between carbon skeletons and folate chemistry.

Grouped by the atlas’s curated pathway map. The table order is not a proven reaction order.

Its proteins

ProteinECReaction (UniProt)Metal or clusterAmino acidsCertainty
Probable glycine dehydrogenase (decarboxylating) subunit 21.4.4.2N(6)-[(R)-lipoyl]-L-lysyl-[glycine-cleavage complex H protein] + glycine + H(+) = N(6)-[(R)-S(8)-aminomethyldihydrolipoyl]-L-lysyl-[glycine-cleavage complex H protein] + CO2—482Step named

Also part of this pathway

These proteins are described under another pathway, but also take part here.

ProteinECReaction (UniProt)Metal or clusterAmino acidsCertainty
Probable glycine dehydrogenase (decarboxylating) subunit 1Home: Folate-linked carbon transfer1.4.4.2N(6)-[(R)-lipoyl]-L-lysyl-[glycine-cleavage complex H protein] + glycine + H(+) = N(6)-[(R)-S(8)-aminomethyldihydrolipoyl]-L-lysyl-[glycine-cleavage complex H protein] + CO2—439Step named
AminomethyltransferaseHome: Folate-linked carbon transfer2.1.2.10N(6)-[(R)-S(8)-aminomethyldihydrolipoyl]-L-lysyl-[protein] + (6S)-5,6,7,8-tetrahydrofolate = N(6)-[(R)-dihydrolipoyl]-L-lysyl-[protein] + (6R)-5,10-methylene-5,6,7,8-tetrahydrofolate + NH4(+)—350Step named
5,10-methylenetetrahydrofolate reductaseHome: Folate and pterin chemistry1.5.1.54(6S)-5-methyl-5,6,7,8-tetrahydrofolate + NAD(+) = (6R)-5,10-methylene-5,6,7,8-tetrahydrofolate + NADH + H(+)—296Step named
Bifunctional protein FolDHome: Folate and pterin chemistry1.5.1.5; 3.5.4.9(6R)-5,10-methylene-5,6,7,8-tetrahydrofolate + NADP(+) = (6R)-5,10-methenyltetrahydrofolate + NADPH—291Step named

Origins

How could single carbon atoms have been carried and added before folate existed?

How it was discovered

  1. 1940sFolate is first isolated, from green leaves, liver and yeast.Horton et al., Principles of Biochemistry, p. 291
Naturalistic proposal

None of the books searched describes a prebiotic route to folate or to its one-carbon chemistry.

Design analysis

Formyl-tetrahydrofolate supplies two of the carbon atoms of the purine ring, so making DNA and RNA letters depends on this cofactor. Folate itself is a complex molecule built by its own pathway.

From the books: Horton et al., Principles of Biochemistry, p. 291; Zubay, Origins of Life on Earth and in the Cosmos, p. 226.

The wider question for this part of the cell: origins for manufacturing cofactors and vitamins.

Sources

Other pathways in this group: Heme and quinones · Biotin and lipoate · NAD and flavins · Thiamine and pyridoxal · Folate and pterin chemistry · Lipid and cofactor connections · Coenzyme A · Aspartate-family branches · Amino-acid connections · Serine, glycine and sulfur · Folate biosynthesis · Oxidative phosphorylation · Thiamine metabolism · Pantothenate and CoA biosynthesis · Glycine, serine and threonine metabolism · Riboflavin metabolism · Nicotinate and nicotinamide metabolism · Biotin metabolism · Cysteine and methionine metabolism · Porphyrin metabolism · Pyruvate metabolism · Not yet placed in a pathway