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Metabolic pathways include several long and complex molecular and chemical reactions including glycolysis and the citric acid cycle. These are present in all three domains of living things and were present in the last universal ancestor. The universal ancestor is the prokaryotic cell and is probably a methanogen that has extensive amino acid, nucleotide, carbohydrate and lipid metabolism.

Evolution of metabolism

Over centuries and time, the retention of these ancient pathways may be the result of these reactions being an optimal solution to their particular metabolic problems. For example, glycolysis and the citric acid cycle produce their end products highly efficiently and in a minimal number of steps. This economy and optimal situation has led to the evolution of these reactions over time.

Evolution of Kreb’s cycle or citric acid cycle

The evolutionary origin of the Krebs citric acid cycle (Krebs cycle) has long been a model case in the understanding of the origin and evolution of metabolic pathways. Although the chemical steps of the cycle are preserved intact throughout nature, diverse organisms make diverse use of its chemistry. In some cases organisms use only selected portions of the cycle.

The origins of key reactions are found in the more primitive anaerobic organisms of the past. Two branches of the Krebs cycle, the oxidative branch and the reductive branch can be linked by the 2-oxoglutarate oxidoreductase system.


More than one hypothesis has been proposed to explain the evolution of metabolic pathways. These include the sequential addition of novel enzymes to a much shorter earlier pathways as well as the recruitment of pre-existing enzymes and their assembly into a novel reaction pathway.

Genomic studies have shown that enzymes in a pathway are likely to have a shared ancestry, suggesting that many pathways have evolved in a step-by-step fashion. Along the development of the pathways novel functions were created from pre-existing steps in the pathway.

An alternative hypothesis comes from studies that trace the evolution of proteins' structures in metabolic networks. This shows that enzymes are pervasively recruited. This recruitment processes result in an evolutionary enzymatic mosaic.

There is also a possibility that some parts of metabolism might exist as "modules" that can be reused in different pathways and perform similar functions on different molecules. Some of the functions and parts of the pathways that are not essential for survival are lost along evolution as well.


  1. http://web.udl.cat/usuaris/pg193845/RARAGCMJES1.pdf
  2. http://ftp.ks.uiuc.edu/Publications/Papers/PDF/FORS99B/FORS99B.pdf
  3. www.stats.ox.ac.uk/__data/assets/file/0013/3343/giannoulatou.pdf
  4. http://www.pnas.org/content/87/1/200.full.pdf
  5. mywebspace.wisc.edu/…/NebertCYP450.pdf

Further Reading

  • All Metabolism Content
  • What is Anabolism?
  • What is Metabolism?
  • Science of Metabolism
  • Metabolism Key Biochemicals

Last Updated: Feb 26, 2019

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