S-Adenosylhomocysteine hydrolase in human and rat liver is localized to the cytosol fraction of the tissue homogenate.

S-Adenosylhomocysteine (SAH) is formed from S-adenosylmethionine (SAM) upon transmethylation using SAM as a methyl donor [ 11. SAH is a potent inhibitor to a wide group of methyl-transfer reactions and has been suggested to be a regulator of biological methylations [2-71. The tissue level of SAH is regulated by the enzyme S-adenosylhomocysteinase (EC 3.3 .I. 1). This enzyme catalyzes the reversible synthesis of SAH from adenosine and L-homocysteine and the equilibrium of the reaction is far in the direction of condensation [8]. The metabolic flow has been suggested to be in the hydrolytic direction [9] and the enzyme catalyzes the first step in the degradation of SAH. No study has been devoted to the subcellular localization of S-adenosylhomocysteinase. Data have been presented [lo] suggesting that the post-microsomal supernatant fraction contains almost all of the S-adenosylhomocysteine synthase activity, but a substantial amount was associated with the ‘nuclear’ fraction. This finding seems interesting in the light of the finding that SAH is a potent inhibitor of DNA methylation in isolated rat liver nuclei [ 1 I]. However, in this report data are presented showing that S-adenosylhomocysteine hydrolase activity is localized exclusively to the soluble fraction of tissue homogenates from human and rat liver.