S‐Adenosylmethionine

George D Markham, The Institute for Cancer Research, Philadelphia, Pennsylvania, USA

Published online: April 2010

DOI: 10.1002/9780470015902.a0000662.pub2

S-adenosylmethionine is one of the few sulfonium ions found in nature and it plays essential roles in the metabolism of all known organisms. The positively charged sulfonium centre endows S-adenosylmethionine with a chemical versatility matched by few other biochemicals, perhaps exceeding even adenosine triphosphate (ATP). S-adenosylmethionine is used in a multitude of metabolic pathways, and the types of chemical reactions in which it partakes are highly varied, ranging from alkylation to free-radical formation. S-sdenosylmethionine is methyl donor in many biosynthetic reactions, whereas methylation of both deoxyribonucleic acid(DNA) and proteins is part of the epigenetic control of cell growth and development. In other pathways, the propylamine moiety is incorporated into the pervasive polyamines spermidine and spermine. Unusual reactions consume S-adenosylmethionine in the formation of plant growth factor ethylene, of cyclopropane fatty acids and in sulfur insertion in the biosynthesis of biotin, lipoic acid and thiamine. S-adenosylmethionine appears to be one of the molecules required for life.

Key concepts:

  • S-adenosylmethionine is a branch point compound with components from purine, amino acid and reduced sulfur metabolism, and thus is potentially able to coordinate these three areas of metabolism. S-adenosylmethionine appears to be required for life.
  • The sulfonium centre of S-adenosylmethionine is able to transfer any of the three attached alkyl groups, providing a metabolic versatility matched by few other biological molecules.
  • S-adenosylmethionine is a progenitor of free radicals that occur as protein-bound reaction intermediates in unusual chemical transformations catalysed by the ‘Radical SAM’: family of enzymes.
  • S-adenosylmethionine metabolism is commonly disrupted in liver disease, and hereditary defects have been found in a few patients with abnormal sulfur metabolism.
  • S-adenosylmethionine is under investigation as a potential drug in treatment of depression, arthritis and liver disease.

Keywords: coenzymes and cofactors; methylation; free radicals; nucleosides; quorum sensing; polyamines

Figure 1. Structure of S-adenosylmethionine (AdoMet or SAM). The sulfur of l-methionine is connected in a sulfonium linkage to the carbon 5¢ of 5¢-deoxyadenosine that is derived from ATP. The stereochemical configuration at the sulfur in enyzmatically formed S-adenosylmethionine is (S); however S-adenosylmethionine spontaneously racemises to the inactive (R)-isomer over a period of a few days. The carbons attached to the positively charged sulfur are electrophilic and readily transferred to basic compounds.
Figure 2. Illustration of metabolic roles of S-adenosylmethionine. The predominant sulfur-containing products of biosynthesis are S-adenosylhomocysteine (SAH) and 5¢-methylthioadenosine (MTA), which have important roles in metabolic regulation as well as the cellular conservation and interconversion of reduced sulfur.
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Related Sub-Topics:

Basic Cell Biology, Protein, RNA and DNA | Chromosomes and Chromatin Modifications | Other Biomolecules: Structure, Function, Metabolism
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Article Title: S‐Adenosylmethionine
 
How to Cite close
Markham, George D(Apr 2010) S‐Adenosylmethionine. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0000662.pub2]