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Pathway · 12 proteins

Heme and quinones

Supply redox-active components to respiratory enzymes.

How it works

  1. Haem branches from uroporphyrinogen III. Uroporphyrinogen-III synthase and a C-methyltransferase build the intermediates, uroporphyrinogen decarboxylase removes four carboxylates, and ferrochelatase inserts iron to give haem.
  2. VF5 also carries a precorrin-2 dehydrogenase/sirohydrochlorin ferrochelatase family protein, which routes the same branch toward sirohaem rather than haem, so the two products compete for shared intermediates.
  3. Menaquinone is built through the futalosine route, marked here by aminofutalosine synthase MqnE and cyclic dehypoxanthinyl futalosine synthase, a bacterial variant that does not start from chorismate. Haem and quinones are the redox cofactors of the respiratory chains in system 3.

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
Chorismate dehydratase4.2.1.151chorismate = 3-[(1-carboxyvinyl)-oxy]benzoate + H2O—236Step named
precorrin-2 dehydrogenase1.3.1.76precorrin-2 + NAD(+) = sirohydrochlorin + NADH + 2 H(+)—187Step named
Uncharacterized protein aq_1612———486Step named
Uroporphyrinogen-III synthase4.2.1.75hydroxymethylbilane = uroporphyrinogen III + H2O—250Step named
Coproporphyrinogen III oxidase1.3.3.15coproporphyrinogen III + 3 O2 = coproporphyrin III + 3 H2O2—436Step named
uroporphyrinogen-III C-methyltransferase2.1.1.107——244Step named
Delta-aminolevulinic acid dehydratase4.2.1.242 5-aminolevulinate = porphobilinogen + 2 H2O + H(+)Zn(2+), Mg(2+)330Step named
Oxygen-independent coproporphyrinogen III oxidase1.3.98.3coproporphyrinogen III + 2 S-adenosyl-L-methionine = protoporphyrinogen IX + 2 5'-deoxyadenosine + 2 L-methionine + 2 CO2[4Fe-4S] cluster456Step named
Uroporphyrinogen decarboxylase4.1.1.37uroporphyrinogen III + 4 H(+) = coproporphyrinogen III + 4 CO2—338Step named
Aminodeoxyfutalosine synthase2.5.1.1203-[(1-carboxyvinyl)-oxy]benzoate + S-adenosyl-L-methionine + H2O = 6-amino-6-deoxyfutalosine + hydrogencarbonate + L-methionine + H(+)[4Fe-4S] cluster371Step named
Cyclic dehypoxanthine futalosine synthase1.21.98.1dehypoxanthine futalosine + S-adenosyl-L-methionine = cyclic dehypoxanthinylfutalosinate + 5'-deoxyadenosine + L-methionine + H(+)[4Fe-4S] cluster361Step named
Ferrochelatase4.98.1.1heme b + 2 H(+) = protoporphyrin IX + Fe(2+)Fe cation309Step named

Origins

Could heme and the quinones that carry electrons have been available before these pathways existed?

Naturalistic proposal

Porphyrins, the ring systems of heme, have not been convincingly made under simulated prebiotic conditions. A major review of prebiotic chemistry leaves porphyrins, flavins and quinones aside for lack of detailed results.

Design analysis

In bacteria the heme pathway starts from glutamate attached to a transfer RNA, the same activated form used to make proteins. Heme production thus draws on the translation machinery, while translation and energy production in turn need heme-containing proteins.

Twelve proteins of the minimal set serve this pathway.

From the books: Garrett & Grisham, Biochemistry, p. 665; Ruiz-Mirazo et al., Prebiotic Systems Chemistry, PDF p. 5; Zubay, Origins of Life on Earth and in the Cosmos, p. 542.

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

Sources

Other pathways in this group: 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 · 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