title: AMP activation of snake muscle fructose 1,6-bisphosphatase at alkaline pH.
abstract: AMP, an allosteric inhibitor at neutral pH, activates snakes muscle fructose 1,6-bisphosphatase at pH 9.2. The activation is virtually unique for the snake muscle enzyme: activation was not observed for the enzymes from either human and rabbit liver or porcine kidney. The activation is Mg(2+)-dependent but was not observed until the concentration of Mg2+ reaches 1 mM. It is known that subtilisin, trypsin, or lysosomal proteases hydrolyse the N-terminal loop of fructose-1,6-bisphosphatase in the vicinity of amino acid residue 60 generating a form of the enzyme with a pH optimum at 9.2. In the presence of AMP, the pH profile of the native snake muscle enzyme resembles that of the alkaline form and modification of the highly reactive sulfhydryl group abolishes AMP activation. The fact that AMP has a dual function at different pH levels suggests that pH might be an important factor in regulating the activity of the enzyme upon binding of AMP at the allosteric site. Indeed, the mode of AMP binding to the allosteric site may differ at neutral and alkaline pH levels. A residue that ionizes with a pKa of 8.9 might be involved in this process.
authors.affiliation: Shanghai Institute of Biochemistry, Academia Sinica, China.
authors.forename: F K
authors.initials: FK
authors.lastname: Zhao
authors.forename: S Q
authors.initials: SQ
authors.lastname: Xu
authors.forename: G J
authors.initials: GJ
authors.lastname: Xu
mesh_terms: D000249:Adenosine Monophosphate / Q000031:analogs & derivatives / Q000494:pharmacology*; D000468:Alkalies; D000494:Allosteric Regulation; D000818:Animals; D003545:Cysteine / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation; D006597:Fructose-Bisphosphatase / Q000187:drug effects*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D009132:Muscles / Q000201:enzymology*; D010446:Peptide Fragments / Q000378:metabolism; D011817:Rabbits; D012911:Snakes; D013045:Species Specificity; D013439:Sulfhydryl Reagents; D013552:Swine
chemical_list: D000468:Alkalies; D010446:Peptide Fragments; D013439:Sulfhydryl Reagents; D000249:Adenosine Monophosphate; D006597:Fructose-Bisphosphatase; D003545:Cysteine