Pathway · 6 proteins
NAD and flavins
Generate redox and electron-transfer cofactors.
How it works
- NAD can be reached from nicotinate through nicotinate phosphoribosyltransferase, or from quinolinate made by quinolinate synthase NadA; both routes converge on nicotinate mononucleotide.
- Nicotinate-nucleotide adenylyltransferase converts the mononucleotide into NAD, and the module also carries a carboxylating nicotinate-nucleotide diphosphorylase.
- Riboflavin is assembled by riboflavin synthase and then converted to FMN and FAD by a bifunctional riboflavin kinase/FAD synthetase. These cofactors reappear as the prosthetic groups of the dehydrogenases, reductases and oxidoreductases described in other systems.
Grouped by the atlas’s curated pathway map. The table order is not a proven reaction order.
Its proteins
| Protein | EC | Reaction (UniProt) | Metal or cluster | Amino acids | Certainty |
|---|---|---|---|---|---|
| Probable nicotinate-nucleotide adenylyltransferase | 2.7.7.18 | nicotinate beta-D-ribonucleotide + ATP + H(+) = deamido-NAD(+) + diphosphate | — | 168 | Step named |
| Nicotinate phosphoribosyltransferase | 6.3.4.21 | 5-phospho-alpha-D-ribose 1-diphosphate + nicotinate + ATP + H2O = nicotinate beta-D-ribonucleotide + ADP + phosphate + diphosphate | — | 426 | Step named |
| Riboflavin biosynthesis protein | 2.7.1.26; 2.7.7.2 | FMN + ATP + H(+) = FAD + diphosphate | — | 314 | Step named |
| Riboflavin synthase | 2.5.1.9 | 2 6,7-dimethyl-8-(1-D-ribityl)lumazine + H(+) = 5-amino-6-(D-ribitylamino)uracil + riboflavin | — | 207 | Step named |
| Quinolinate synthase | 2.5.1.72 | iminosuccinate + dihydroxyacetone phosphate = quinolinate + phosphate + 2 H2O + H(+) | [4Fe-4S] cluster | 322 | Step named |
| Probable nicotinate-nucleotide pyrophosphorylase [carboxylating] | 2.4.2.19 | nicotinate beta-D-ribonucleotide + CO2 + diphosphate = quinolinate + 5-phospho-alpha-D-ribose 1-diphosphate + 2 H(+) | — | 274 | Step named |
Origins
Could NAD and the flavins, which carry electrons in almost every pathway, have been available before cells?
Adenine forms readily when ammonia and hydrogen cyanide condense, and the nicotinamide part of NAD can be reached by several routes from plausibly prebiotic chemicals (Friedmann et al. 1971; Cleaves and Miller 2001).
Making a part is not making the whole cofactor: the books report no prebiotic synthesis of complete NAD or FAD.
In the cell these cofactors are built and recycled by six proteins in this group alone, and nearly every other pathway depends on them.
From the books: Ribas de Pouplana (ed.), The Genetic Code and the Origin of Life, p. 67; Atkins, Gesteland & Cech (eds.), RNA Worlds, p. 48; Alberts et al., Molecular Biology of the Cell, p. 76.
The wider question for this part of the cell: origins for manufacturing cofactors and vitamins.
Sources
- Atlas pathway grouping from the VF5 reference-genome system map (Deckert et al. 1998; Braakman & Smith 2014)
Other pathways in this group: Heme and quinones · Biotin and lipoate · 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