one-carbon metabolism activated methyl cycle S-adenosylmethionine cycle UPa:UPA00450 SAM cycle The activated methyl donor involved in most biosynthetic methylation is usually S-adenosylmethionine (SAM). SAM is synthesized by the transfer of an adenosyl group from ATP to the sulfur atom of methionine. The methyl group of the methionine unit is activated by the positive charge on the adjacent sulfur atom, which makes the molecule much more reactive than N5-methyltetrahydrofolate. The synthesis of S-adenosylmethionine is unusual in that the triphosphate group of ATP is split into pyrophosphate and orthophosphate; the pyrophosphate is subsequently hydrolyzed to two molecules of Pi. S-Adenosylhomocysteine is formed when the methyl group of S-adenosylmethionine is transferred to an acceptor. S-Adenosylhomocysteine is then hydrolyzed to homocysteine and adenosine. Methionine can be regenerated by the transfer of a methyl group to homocysteine. [Stryer, Biochemistry, 2002]. GO:0033353 pathway