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Updated: Jun 17, 2026

Metabolic Pathway Confirmation and Discovery Through 13C-labeling of Proteinogenic Amino Acids
Published on: January 26, 2012
Analysis of the intermediary metabolism of a reductive chemoautotroph
Vijayasarathy Srinivasan1, Harold J Morowitz
1Krasnow Institute for Advanced Studies, George Mason University, Fairfax, Virginia 22030, USA. vsriniva@gmu.edu
Abstract:
All extant life forms depend, directly or indirectly, on the autotrophic fixation of the dominant elements of the biosphere: carbon, hydrogen, nitrogen, oxygen, phosphorus, and sulfur. We have earlier presented the canonical network of reactions that constitute the anabolism of a reductive chemoautotroph. Separating this network into subgraphs reveals several empirical generalizations: (1) acetate (acetyl-CoA), pyruvate, phosphoenol pyruvate, oxaloacetate, and 2-oxoglutarate serve as universal starting points for all pathways leading to the universal building blocks-20 amino acids and 4 ribonucleotide triphosphates; (2) all pathways are anabolic; (3) all reactions operate by complete utilization of outputs with no molecules left behind as waste, ensuring conservation of information; (4) the core metabolome of 120 compounds is acidic, consisting of compounds containing phosphoric or carboxylic acid or both; and (5) the core network is both brittle-vulnerable to a single break-and robust-having persisted for 4 billion years. Preliminary analysis of the chemical reactions and resultant structures reveals (a) a sparseness among possible molecular structures; (b) subdomains in the network; and (c) restriction of anabolism to a small set of rudimentary organic reactions with limited diversity in chemical mechanisms. These generalizations have implications for biogenesis and trophic ecology.
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