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Pathway · 3 proteins

Aspartate-family branches

Routes connect aspartate chemistry to several amino acids.

How it works

  1. Oxaloacetate connects central carbon metabolism to aspartate formation.
  2. Aspartate-family routes branch through activated and reduced intermediates. Lysine synthesis proceeds through diaminopimelate-related chemistry in the selected bacterial example; threonine production uses homoserine-related steps.
  3. Methionine, lysine and threonine are different endpoint branches, not consecutive products of one linear pathway. Homologous enzymes can have different substrate ranges, so annotations need pathway-specific confirmation.

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
Diaminopimelate decarboxylase4.1.1.20meso-2,6-diaminopimelate + H(+) = L-lysine + CO2—420Step named
LL-diaminopimelate aminotransferase2.6.1.83(2S,6S)-2,6-diaminopimelate + 2-oxoglutarate = (S)-2,3,4,5-tetrahydrodipicolinate + L-glutamate + H2O + H(+)—387Step named
Threonine synthase4.2.3.1O-phospho-L-homoserine + H2O = L-threonine + phosphate—409Step named

Also part of this pathway

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

ProteinECReaction (UniProt)Metal or clusterAmino acidsCertainty
AspartokinaseHome: Aspartate-family branches2.7.2.4L-aspartate + ATP = 4-phospho-L-aspartate + ADP—415Step named
Homoserine kinaseHome: Aspartate-family branches2.7.1.39L-homoserine + ATP = O-phospho-L-homoserine + ADP + H(+)—297Step named
Homoserine dehydrogenaseHome: Aspartate-family branches1.1.1.3L-homoserine + NADP(+) = L-aspartate 4-semialdehyde + NADPH + H(+)—435Step named
Diaminopimelate epimeraseHome: Aspartate-family branches5.1.1.7(2S,6S)-2,6-diaminopimelate = meso-2,6-diaminopimelate—279Step named
Aspartate-semialdehyde dehydrogenaseHome: Aspartate-family branches1.2.1.11L-aspartate 4-semialdehyde + phosphate + NADP(+) = 4-phospho-L-aspartate + NADPH + H(+)—340Step named
UDP-N-acetylmuramoyl-L-alanyl-D-glutamate--2,6-diaminopimelate ligaseHome: Peptidoglycan precursors6.3.2.13UDP-N-acetyl-alpha-D-muramoyl-L-alanyl-D-glutamate + meso-2,6-diaminopimelate + ATP = UDP-N-acetyl-alpha-D-muramoyl-L-alanyl-gamma-D-glutamyl-meso-2,6-diaminopimelate + ADP + phosphate + H(+)Mg(2+)482Step named

Origins

Could aspartate and the amino acids made from it have been available before these branches existed?

Naturalistic proposal

Aspartic acid can be produced under simulated prebiotic conditions and is counted among the amino acids that could have been available first. Zubay discusses how carbohydrates could have supplied carbon skeletons for many amino acids on the early Earth.

Design analysis

From aspartate the cell makes lysine, methionine, threonine and isoleucine. In E. coli the first step is carried out by three versions of the same enzyme, each switched off by a different end product, so that one product cannot shut down the supply of the others.

From the books: Rogers, Integrated Molecular Evolution, p. 91; Zubay, Origins of Life on Earth and in the Cosmos, p. 283; Nelson & Cox, Lehninger Principles of Biochemistry, p. 872.

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 · 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