The mechanism of end product inhibition of serine biosynthesis. V. Mechanism of serim inhibition of phosphoglycerate dehydrogenases.
The reduction of enzyme-bound DPN constitutes a half-reaction of phosphoglycerate dehydrogenase and has been investigated fluorometrically. Serine was found to inhibit the half-reaction to the same extent and with the same degree of cooperation as the steady state reaction. This finding identifies the ternary complex conversion as the point in the reaction sequence at which serine inhibition occurs. Delta H determinations for the half-reaction showed no difference whether serine was or was not present and led to the conclusion that the inhibitory effect of serine could only manifest itself through the delta S term in the expression for the formation of the activated transition state complex. DL-3-P[2-2H]glyceric acid showed no primary isotope effect in the half-reaction. This result excludes hydrogen transfer as the rate-limiting step in the half-reaction and confirms that an isomerization step, affected by serine, exists in the ternary complex conversion scheme. The deuterated 3-P-glyceric acid shows an isotope effect of 2 in the steady state reaction.
D000429:Alcohol Oxidoreductases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D003903:Deuterium; D004926:Escherichia coli / Q000201:enzymology; D005988:Glyceric Acids / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D009243:NAD; D009943:Organophosphorus Compounds; D011485:Protein Binding; D012694:Serine / Q000096:biosynthesis / Q000494:pharmacology*; D013816:Thermodynamics
D005988:Glyceric Acids; D009943:Organophosphorus Compounds; D009243:NAD; D012694:Serine; D003903:Deuterium; D000429:Alcohol Oxidoreductases