title: Inactivation of S-adenosyl-L-homocysteine hydrolase by cAMP results from dissociation of enzyme-bound NAD+.
abstract: S-Adenosyl-L-homocysteine hydrolase (EC 3.3.1.1) is inactivated by cAMP and also by 2'-deoxyadenosine, and in both cases, activity is restored by incubating the inactivated enzyme with NAD+. We have previously presented evidence that, despite these similarities, inactivation by these two ligands proceeds by different mechanisms. We have now used a fluorescence technique to quantitate enzyme-bound NAD+ and NADH on S-adenosyl-L-homocysteine hydrolase from Dictyostelium discoideum, and we have confirmed that cAMP and 2'-deoxyadenosine inactivate by different mechanisms. Whereas inactivation by 2'-deoxyadenosine is due to reduction of the enzyme-bound NAD+ to NADH, incubation of S-adenosyl-L-homocysteine hydrolase with cAMP results in dissociation of the enzyme-bound NAD+. The dissociation is reversible, and reactivation likely occurs by restoration of the initial NAD+ content. This reversible inactivation by cAMP may be a mechanism of controlling biological methylation reactions by adjusting intracellular concentrations of S-adenosyl-L-homocysteine through action of S-adenosyl-L-homocysteine hydrolase.
authors.forename: R J
authors.initials: RJ
authors.lastname: Hohman
authors.forename: M C
authors.initials: MC
authors.lastname: Guitton
authors.forename: M
authors.initials: M
authors.lastname: Veron
mesh_terms: D043383:Adenosylhomocysteinase; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000494:pharmacology*; D003839:Deoxyadenosines / Q000494:pharmacology; D004023:Dictyostelium / Q000201:enzymology; D006867:Hydrolases / Q000037:antagonists & inhibitors*; D007700:Kinetics; D009243:NAD / Q000378:metabolism*; D010084:Oxidation-Reduction; D011485:Protein Binding; D013050:Spectrometry, Fluorescence / Q000379:methods
chemical_list: D003839:Deoxyadenosines; D009243:NAD; D000242:Cyclic AMP; D006867:Hydrolases; D043383:Adenosylhomocysteinase