title: Regulation of human lymphocyte S-adenosylmethionine synthetase by product inhibition.
abstract: A steady-state kinetic analysis of human S-adenosylmethionine synthetase indicates that the reaction is Bi Ter with ordered addition of ATP and L-methionine and release of S-adenosylmethionine as the first product. Pyrophosphate and phosphate are then released randomly. I-Parabolic inhibition by phosphate with respect to ATP indicates that this product must bind to more than one site. A model in which phosphate binds to the pyrophosphate site gives a rate equation that is consistent with the kinetic data. Values have been determined for those constants in the equation that are large enough to evaluate, and the in vitro kinetic behavior of S-adenosylmethionine synthetase can be predicted at substrate and product concentrations that are expected intracellularly. Inhibition by combinations of products, especially pyrophosphate and phosphate, is synergistic. Of particular interest is the ability of pyrophosphate and phosphate to increase the sensitivity of the enzyme to inhibition by S-adenosylmethionine. This phenomenon may play a role in regulating steady-state cellular concentrations of S-adenosylmethionine.
authors.affiliation: Department of Medicine, Duke University Medical Center, Durham, NC.
authors.forename: M
authors.initials: M
authors.lastname: Kotb
authors.forename: N M
authors.initials: NM
authors.lastname: Kredich
mesh_terms: D011756:Diphosphates / Q000378:metabolism / Q000494:pharmacology; D006706:Homeostasis; D006801:Humans; D007700:Kinetics; D008214:Lymphocytes / Q000201:enzymology*; D008433:Mathematics; D008716:Methionine Adenosyltransferase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D008962:Models, Theoretical; D010710:Phosphates / Q000378:metabolism / Q000494:pharmacology; D012436:S-Adenosylmethionine / Q000378:metabolism / Q000494:pharmacology; D014166:Transferases / Q000378:metabolism*
chemical_list: D011756:Diphosphates; D010710:Phosphates; D012436:S-Adenosylmethionine; D014166:Transferases; D008716:Methionine Adenosyltransferase