The interaction and inhibition of muscle lactate dehydrogenase by the alkaloid caffeine.
Kinetic analysis showed that the alkaloid caffeine is a competitive inhibitor of the enzyme lactate dehydrogenase with respect to substrate pyruvate, and a non-competitive inhibitor with respect to the coenzyme NADH. The inhibitor constant Ki is 0,54 mM. Scatchard analysis determined the dissociation constant for a single independent binding site of the ternary lactate dehydrogenase - NADH - caffeine complex (KE-NADH-CAFFEINE) and the number of binding sites to be 0,14 mM and 3,83 respectively. Caffeine binds to a hydrophobic domain in the substrate binding site. Alternate nucleophilic - electrophilic functionalities within the inhibitor molecule are proposed to be the fundamental reason for the inhibition.
D000818:Animals; D001665:Binding Sites; D001667:Binding, Competitive; D002110:Caffeine / Q000378:metabolism / Q000494:pharmacology*; D007700:Kinetics; D007770:L-Lactate Dehydrogenase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D009132:Muscles / Q000201:enzymology*; D009243:NAD / Q000378:metabolism; D011773:Pyruvates / Q000378:metabolism; D019289:Pyruvic Acid; D011817:Rabbits
D011773:Pyruvates; D009243:NAD; D002110:Caffeine; D019289:Pyruvic Acid; D007770:L-Lactate Dehydrogenase