Pathway · 8 proteins
Branched-chain amino acids
Pyruvate-linked chemistry supplies valine, leucine and isoleucine branches.
How it works
- Pyruvate supplies branched-chain amino-acid chemistry. Valine and leucine share intermediates, while isoleucine requires an appropriate precursor route.
- The Aquifex discussion includes a citramalate route toward isoleucine precursors; the common threonine-deamination route must not automatically be assigned to VF5.
- Condensation, rearrangement, dehydration and amino-group transfer contribute to the branches. Leucine synthesis extends a ketoacid intermediate through additional reactions.
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 |
|---|---|---|---|---|---|
| Ketol-acid reductoisomerase (NADP(+)) | 1.1.1.86 | (2R)-2,3-dihydroxy-3-methylbutanoate + NADP(+) = (2S)-2-acetolactate + NADPH + H(+) | Mg(2+) | 333 | Step named |
| 3-isopropylmalate dehydratase small subunit | 4.2.1.33 | (2R,3S)-3-isopropylmalate = (2S)-2-isopropylmalate | — | 168 | Step named |
| Acetolactate synthase small subunit | 2.2.1.6 | 2 pyruvate + H(+) = (2S)-2-acetolactate + CO2 | — | 192 | Step named |
| 2-isopropylmalate synthase | 2.3.3.13 | 3-methyl-2-oxobutanoate + acetyl-CoA + H2O = (2S)-2-isopropylmalate + CoA + H(+) | Mn(2+) | 520 | Step named |
| 3-isopropylmalate dehydrogenase | 1.1.1.85 | (2R,3S)-3-isopropylmalate + NAD(+) = 4-methyl-2-oxopentanoate + CO2 + NADH | Mg(2+), Mn(2+) | 364 | Step named |
| (R)-citramalate synthase | 2.3.3.21 | pyruvate + acetyl-CoA + H2O = (3R)-citramalate + CoA + H(+) | — | 528 | Step named |
| Dihydroxy-acid dehydratase | 4.2.1.9 | (2R)-2,3-dihydroxy-3-methylbutanoate = 3-methyl-2-oxobutanoate + H2O | Mg(2+), [2Fe-2S] cluster | 555 | Step named |
| 3-isopropylmalate dehydratase large subunit | 4.2.1.33 | (2R,3S)-3-isopropylmalate = (2S)-2-isopropylmalate | [4Fe-4S] cluster | 432 | Step named |
Also part of this pathway
These proteins are described under another pathway, but also take part here.
| Protein | EC | Reaction (UniProt) | Metal or cluster | Amino acids | Certainty |
|---|---|---|---|---|---|
| Acetolactate synthaseHome: Pantothenate and CoA biosynthesis | 2.2.1.6 | 2 pyruvate + H(+) = (2S)-2-acetolactate + CO2 | Mg(2+) | 585 | Step named |
Origins
Could valine, leucine and isoleucine have been supplied before the pathways that make them existed?
Valine is among the amino acids that can form under simulated prebiotic conditions, and is listed among those thought to be available first.
The first enzyme on the way from threonine to isoleucine is switched off by isoleucine itself. It was one of the first examples of feedback inhibition ever found: the end of the pathway controls its beginning.
Leucine, isoleucine and valine share several enzymes, so supply of each must be balanced against the others.
From the books: Rogers, Integrated Molecular Evolution, p. 91; Nelson & Cox, Lehninger Principles of Biochemistry, p. 872.
The wider question for this part of the cell: origins for making the twenty amino acids.
Sources
- Atlas pathway grouping from the VF5 reference-genome system map (Deckert et al. 1998; Braakman & Smith 2014)
Other pathways in this group: Aromatic amino acids · Aspartate-family branches · Nitrogen assimilation · RNA maturation · Folate-linked carbon transfer · Arginine biosynthesis · Cysteine and methionine metabolism · Histidine metabolism · Lysine biosynthesis · Arginine and proline metabolism · Phenylalanine, tyrosine and tryptophan biosynthesis · Not yet placed in a pathway