Part of the cell · Amino-acid biosynthesis
Making the twenty amino acids
On the cell picture: Amino acid biosynthesis
Proteins are chains of amino acids, and the medium supplies none of them. The cell has to manufacture all twenty from scratch.
THE BIG PICTURE
Follow the amino-acid map
Start with a carbon skeleton. Add nitrogen. Trace what happens next.
A teaching overview, not a complete reaction map. Biosynthetic branches reflect the Aquifex aeolicus atlas; catabolic entry points summarize core biochemistry, and routes vary among organisms. Pathway links open the detailed pages below.
Proteins in the model: 107
Part of the model's 1051 proteins. Each group below is a book group, counted in the working count after the repeats and non-first-cell groups were removed. The proteins are not yet matched gene by gene.
| Group | Proteins |
|---|---|
| Methionine cycle and SAM/SAH metabolism | 3 |
| Serine biosynthesis | 3 |
| Glycine cleavage system | 4 |
| Serine and sulfide to cysteine | 2 |
| Lysine biosynthesis via diaminopimelate | 6 |
| Alanine metabolism | 2 |
| Valine biosynthesis | 4 |
| Leucine biosynthesis | 6 |
| Isoleucine biosynthesis | 5 |
| Histidine biosynthesis | 9 |
| Tryptophan biosynthesis | 5 |
| Tyrosine biosynthesis | 3 |
| Phenylalanine biosynthesis | 3 |
| Aspartate metabolism | 4 |
| Asparagine metabolism | 2 |
| Methionine biosynthesis | 4 |
| Threonine biosynthesis | 5 |
| Glutamate-related essential group | 5 |
| Expanded glutamate-related | 9 |
| Ornithine and arginine biosynthesis | 4 |
| Ornithine and proline metabolism | 5 |
| Amino acid synthesis regulation | 8 |
| Additional regulation | 1 |
| Urea cycle | 5 |
Its pathways
- Aromatic amino acidsatlas pathway11
- Branched-chain amino acidsatlas pathway8
- Aspartate-family branchesatlas pathway5
- Nitrogen assimilationatlas pathway4
- RNA maturationatlas pathway4
- Folate-linked carbon transferatlas pathway2
- Arginine biosynthesisKEGG map6
- Cysteine and methionine metabolismKEGG map6
- Histidine metabolismKEGG map6
- Lysine biosynthesisKEGG map3
- Arginine and proline metabolismKEGG map3
- Phenylalanine, tyrosine and tryptophan biosynthesisKEGG map3
- Not yet placed in a pathwayto sort31
If it fails
One amino acid goes missing, so protein synthesis stops at the first place that residue is needed — which is fatal within one or two generations.
Starves of a building block · 1–2 generations
What it depends on
- Building carbon into moleculesCentral metabolism provides carbon skeletons for amino acid biosynthesis.Book pp. 498–500
- Manufacturing cofactors and vitaminsCofactors support amino-group transfer, reduction, and other amino acid biosynthetic reactions.Book pp. 498–500
- Turning hydrogen into usable energyATP and reducing power drive energy-requiring amino acid biosynthesis.Book pp. 499–500
- Pulling nutrients in from outsideUptake supplies nitrogen, sulfur, or other environmental substrates needed by the selected biosynthetic routes.Book pp. 500, 502–503
What it supplies
- Manufacturing cofactors and vitaminsAmino-acid-derived precursors contribute to pathways such as SAM and other cofactor biosynthesis.Book pp. 498–500
- Making DNA and RNA lettersAmino acids donate nitrogen and other atoms to purine and pyrimidine biosynthesis.Book pp. 499–500
- Reading genes into RNA, Building proteins and folding themAmino acids are the building blocks loaded onto tRNAs and joined into proteins.Book pp. 500–502
- Loading metals into enzymesCysteine supplies sulfur to selected Fe–S cluster assembly systems.Book pp. 412–414, 500, 505
Dependencies are curated from the book at the level of the map’s systems and are not measured protein contacts. See all systems together.
How it is built and controlled
Counts from UniProt annotations of this group’s proteins.
Its place in the control layer
Information
- Epigenetic information: ,
From the control-layer pages. Which genes a regulator controls is mostly inferred from related bacteria, because Aquifex has no genetic system for testing it directly.
Origins
What needs to be explained
How did sufficiently selective amino-acid production, activation and coded incorporation become integrated?
What needs explaining. Explain amino-acid availability, stereochemical biases and connection to a coding-dependent synthesis system without assuming modern biosynthesis at the outset.
Hurdles
- H-AA-1Supply of all twentyThe problem. Proteins are built from twenty amino acids. Aquifex makes all twenty itself, through pathways of several dozen enzymes.Why it is hard. Experiments and meteorites yield mainly the simplest amino acids, mixed with many that life does not use; tryptophan and the basic amino acids are rare or absent.Chemistry before lifeStage 1: Ingredients made under plausible early-Earth conditionsShown: Spark-discharge experiments and meteorites both give a mixture of amino acids.In the books: 98 open problems on amino acid metabolism ↗
- H-AA-2Chemical compatibilityThe problem. Amino acids must accumulate in one place at useful concentrations, alongside the other building blocks.Why it is hard. In open water they are diluted, and they react with sugars, aldehydes and other molecules present in the same mixtures, which consumes them.Chemistry before lifeStage 0: Not yet addressed by experimentShown: not yet addressed by experiment.In the books: 98 open problems on amino acid metabolism ↗
- H-AA-3One-handednessThe problem. Proteins use only left-handed (L) amino acids. A single right-handed residue disrupts the regular folds proteins depend on.Why it is hard. Chemical syntheses give equal amounts of both hands. Meteorites show only small excesses of one hand, far from the purity proteins require.Chemistry before lifeStage 1: Ingredients made under plausible early-Earth conditionsShown: Meteorites carry small excesses of one handedness; how a full preference became established is not shown.In the books: 98 open problems on amino acid metabolism ↗
- H-AA-4Joining into functional chainsThe problem. Useful proteins are chains of about a hundred or more amino acids in a specific order. In cells they are joined on the ribosome, at the cost of energy for every bond.Why it is hard. Forming a peptide bond in water is uphill, and chains made without a template have random order, so a specific working sequence is not reproduced.Molecular machinesStage 2: One step shown on its ownShown: Wet–dry cycles give short peptide-like chains, without control of sequence (Forsythe et al. 2015).In the books: 98 open problems on amino acid metabolism ↗
- H-AA-5Sequence specificationThe problem. A working protein sequence has to be specified and made again in every generation. In cells the sequence is read from a gene through the genetic code.Why it is hard. Without coded information each chain is a one-off: there is no way to make the same useful sequence a second time.Information and controlStage 0: Not yet addressed by experimentShown: not yet addressed by experiment.In the books: 98 open problems on amino acid metabolism ↗
Scope. The first peptide-forming chemistry need not have used today’s complete twenty-amino-acid set or modern biosynthetic routes.
Experimental progress. A reconstructed biosynthetic network connects carbon assimilation with amino acid, nucleotide, and cofactor production. This provides a systems view of shared chemical inputs; a reconstruction is not an experimental demonstration of the first cell.
What would strengthen a natural account. Steps shown to work together under plausible early-Earth conditions, without a chemist choosing the reagents, purifying the products or changing conditions between steps, would strengthen a natural account of origins in proportion to what they explain. Loss of a claimed dependency or discovery of functional alternatives would weaken the corresponding design argument. Gaps in the record do not supply a numerical likelihood for either explanation.
Observations. Ordered enzyme reactions convert precursors into amino acids used in protein synthesis. Carbon skeletons, nitrogen, cofactors and energy connect this supply to other systems.
Hallmarks that apply.
- H26 Preprogrammed production lines: Ordered enzyme reactions convert precursors into amino acids used in protein synthesis.
- H24 Metabolic integration: Carbon skeletons, nitrogen, cofactors and energy connect this supply to other systems.
- H27 Material selection: Catalysts distinguish substrates and stereochemical products; tRNA charging adds another selection step.
The author’s conclusion. The coordinated features give the author a positive reason to consider design within the wider cellular architecture. For this local system alone, they do not establish that design is uniquely the best historical explanation. The conservative inference is that the system contributes to a cumulative design case, with its weight conditional on the comparative evidence and on how much plausible natural pathways explain.
From the book article Amino Acid Metabolism, with its scientific references.
How it was discovered
- 1953Stanley Miller passes electric sparks through a mixture of gases and obtains several amino acids.Miller, Science 117:528–529 (1953)
- 1956Edwin Umbarger finds that the end product of a pathway can switch off its first enzyme: feedback inhibition in amino acid synthesis.Umbarger, Science 123:848 (1956)
- 1970Amino acids are found in the Murchison meteorite, showing that they can form outside living things.Kvenvolden et al., Nature 228:923–926 (1970)
- 1997Cronin and Pizzarello report a small excess of left-handed forms among some Murchison amino acids.Cronin & Pizzarello, Science 275:951–955 (1997)
- 2008A re-analysis of Miller’s stored samples from a volcanic-style experiment finds more than 20 amino acids.Johnson et al., Science 322:404 (2008)
- 2015Repeated wetting and drying joins amino acids into short peptide-like chains through ester intermediates.Forsythe et al., Angewandte Chemie 54:9871–9875 (2015)
Each hurdle above is sorted by kind and by how far experiments have got (see “How hurdles are sorted” at the top).
All parts of the cell side by side: origins hub. The book articles:
- Amino Acid Metabolism: system page · full description · origins
Sources
- UniProt proteome UP000000798
- KEGG: Aquifex aeolicus
- Alberts et al., Molecular Biology of the Cell, 7th ed., Chapter 2 (Cell Chemistry and Bioenergetics) and Panel 3–1 (The 20 Amino Acids Found in Proteins).
- Nelson & Cox, Lehninger Principles of Biochemistry, 6th ed., Chapters 18 and 22: amino-acid oxidation and biosynthesis.