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Pathway · 6 proteins

Thiamine and pyridoxal

Support carbon-bond and amino-group chemistry.

How it works

  1. Thiamine phosphate synthase joins the thiazole and pyrimidine halves of the molecule. VF5 carries two annotated thiamine-phosphate synthase entries, one of them the YjbQ family, and thiamine-phosphate kinase converts the monophosphate to the active diphosphate.
  2. Pyridoxal 5'-phosphate is made through PdxA, a 4-hydroxythreonine-4-phosphate dehydrogenase, and pyridoxine 5'-phosphate synthase; a pyridoxamine 5'-phosphate oxidase family protein can recycle the amine form back to the aldehyde.
  3. Thiamine diphosphate and pyridoxal phosphate are the cofactors of carbon-bond chemistry and amino-group transfer respectively, so these routes supply transketolase, 2-oxoacid oxidoreductases and the aminotransferases used elsewhere in the atlas.

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
Pyridoxine 5'-phosphate synthase2.6.99.23-amino-2-oxopropyl phosphate + 1-deoxy-D-xylulose 5-phosphate = pyridoxine 5'-phosphate + phosphate + 2 H2O + H(+)1-deoxy-D-xylulose 5-phosphate242Step named
YjbQ family protein———134System only
YjbQ family protein———137System only
Thiamine-monophosphate kinase2.7.4.16thiamine phosphate + ATP = thiamine diphosphate + ADPMg(2+)306Step named
Thiamine-phosphate synthase 12.5.1.32-[(2R,5Z)-2-carboxy-4-methylthiazol-5(2H)-ylidene]ethyl phosphate + 4-amino-2-methyl-5-(diphosphooxymethyl)pyrimidine + 2 H(+) = thiamine phosphate + CO2 + diphosphateMg(2+)215Step named
4-hydroxythreonine-4-phosphate dehydrogenase1.1.1.2624-(phosphooxy)-L-threonine + NAD(+) = 3-amino-2-oxopropyl phosphate + CO2 + NADH—320Step named

Origins

Could thiamine (vitamin B1) and pyridoxal phosphate (vitamin B6) have been available before cells made them?

Naturalistic proposal

Essential coenzymes such as these have not been convincingly made under simulated prebiotic conditions. The books searched describe no prebiotic route to either.

Design analysis

Thiamine pyrophosphate controls its own supply through an RNA switch, the most widespread riboswitch known, found in many bacteria, fungi and some plants.

Pyridoxal phosphate is needed by many enzymes that make and convert amino acids, so the amino-acid pathways cannot run until it is made.

From the books: Garrett & Grisham, Biochemistry, p. 665; Nelson & Cox, Lehninger Principles of Biochemistry, p. 1133.

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 · Folate and pterin chemistry · Lipid and cofactor connections · Coenzyme A · Aspartate-family branches · Amino-acid connections · Folate-linked carbon transfer · 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