Biochemistry of S-Adenosylmethionine
Nomenclature of S-Adenosylmethionine
S-adenosylmethionine is a molecule of adenosine (a nucleoside) attached to the sulfur atom ("S") of methionine (an amino acid). Technically, amino acids exist as either (D) or (L) mirror images, so the biochemically correct name is S-adenosyl-L-methionine. Unfortunately, some abbreviations of S-adenosylmethionine are confusing due to incorrect naming of methionine. The biochemical abbreviations for an amino acid can be written as either a one or three letter code. Thus, methionine can be abbreviated as either "M" or "Met". Similarly, adenosine/adenosyl can be abbreviated as "Ado". Based on these biochemical rules, abbreviations of S-adenosylmethionine that are used in scientific publications include SAM and AdoMet. In contrast, both SAMe and SAM-e are incorrect abbreviations because "Me" denotes a methyl group whereas "M-e" is purely jargon.
S-Adenosylmethionine (SAM) Methyl Cycle
SAM is the primary source of methyl groups (-CH3) that are transferred to chemical substrates, yielding methylated products. Enzymes known as methyltransferases first bind to a substrate and SAM and then transfer the methyl group from SAM to the substrate. Removal of the methyl group from SAM results in a molecule of S-adenosylhomocysteine. The biochemical pathway that is involved in regenerating SAM is shown below. It should be noted that activated forms of vitamins are required to regenerate SAM. Specifically, the conversion of methionine to homocysteine requires folic acid as a precursor to N5-methyltetrahydrofolate and vitamin B12 as a precursor to methylcobalamin.
There are several caveats for supplementing cellular levels of SAM. First, increasing the amount of SAM inside a cell above physiologic levels requires transport of SAM into a cell and trafficking to the correct cellular compartment. Although there is evidence that nucleoside transporters are involved in transport of SAM into a cell (1), the exact targets are unknown. Once inside a cell, SAM interacts with another transporter (2,3) to get into mitochondria. Second, increased levels of cellular SAM result in increased levels of the intermediate compounds S-adenosylhomocysteine, methionine, and (especially) homocysteine. Third, depending on the cell type and concentration of SAM, methylated products may include toxic compounds such as methanol, formaldehyde, and formic acid in addition to the wide range of physiologic compounds such as epinephrine/adrenaline (methylation of norepinephrine/noradrenaline).
References
(1) Chishty M, Reichel A, Abbott NJ, Begley DJ (2002) S-adenosylmethionine is substrate for carrier mediated transport at the blood-brain barrier in vitro. Brain Research 942:46-50.
(2) Marobbio CM, Agrimi G, Lasorsa FM, Palmieri F (2003) Identification and functional reconstitution of yeast mitochondrial carrier for S-adenosylmethionine. EMBO Journal 22:5975-5982.
(3) Agrimi G, Di Noia MA, Marobbio CM, Fiermonte G, Lasorsa FM, Palmieri F (2004) Identification of the human mitochondrial S-adenosylmethionine transporter: bacterial expression, reconstitution, functional characterization and tissue distribution. Biochemical Journal 379:183-190.
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