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Pathway · 4 proteins

Nitrogen assimilation

Glutamate and glutamine connect nitrogen supply to biosynthesis.

How it works

  1. Carbon metabolism supplies 2-oxoglutarate and other carbon skeletons. Usable nitrogen must be incorporated into organic molecules.
  2. Glutamine synthetase uses glutamate, ammonium and ATP to form glutamine. Glutamate synthase can transfer glutamine nitrogen to 2-oxoglutarate, producing glutamate.
  3. Glutamate and glutamine then donate nitrogen to multiple biosynthetic reactions. The exact route and enzyme requirements depend on growth conditions.

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
Glutamine synthetase6.3.1.2L-glutamate + NH4(+) + ATP = L-glutamine + ADP + phosphate + H(+)Mg(2+)469Step named
Glutamate synthase [NADPH] large chain1.4.1.132 L-glutamate + NADP(+) = L-glutamine + 2-oxoglutarate + NADPH + H(+)FMN, [3Fe-4S] cluster1493Step named
Glutamate synthase small subunit gltD———476Step named
Protease I———167System only

Also part of this pathway

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

ProteinECReaction (UniProt)Metal or clusterAmino acidsCertainty
tetrahydrofolate synthaseHome: Folate and pterin chemistry6.3.2.17(6S)-5,6,7,8-tetrahydrofolyl-(gamma-L-Glu)(n) + L-glutamate + ATP = (6S)-5,6,7,8-tetrahydrofolyl-(gamma-L-Glu)(n+1) + ADP + phosphate + H(+)Mg(2+)410Step named

Origins

How could nitrogen have entered organic molecules before there were enzymes to capture ammonia?

How it was discovered

  1. 1953Stanley Miller, working in Harold Urey's laboratory, makes amino acids from a simulated early atmosphere, the start of experimental prebiotic chemistry.Zaikowski & Friedrich (eds.), Chemical Evolution across Space and Time, p. 285
Naturalistic proposal

Before the 1950s, organic syntheses from simple compounds were studied to understand nitrogen assimilation and carbon dioxide fixation in plants, not the origin of life, because the first living things were assumed to be plant-like. Miller's 1953 experiment changed the question: amino acids could form from simple gases and an energy source.

Design analysis

In the cell, ammonia is captured by glutamine synthetase and glutamate synthase. Glutamate synthase passes ammonia from one active site to another through an internal tunnel, which keeps the reactive intermediate away from side reactions. The minimal set needs four proteins for this step alone.

From the books: Zaikowski & Friedrich (eds.), Chemical Evolution across Space and Time, p. 285; Garrett & Grisham, Biochemistry, p. 912.

The wider question for this part of the cell: origins for making the twenty amino acids.

Sources

Other pathways in this group: Aromatic amino acids · Branched-chain amino acids · Aspartate-family branches · 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