Resolution by graphical methods of the equations for allosteric competitive inhibition and activation in Michaelian enzyme and transport systems. Application to the competitive inhibition of glucose transport in brain by phlorizin and phloretin.
A brief exposition of the theory of competition in systems conforming to simple Michaelis-Menten kinetics is given. Emphasis is placed on an operational distinction between: 10 True competition between substrate and inhibitor for a single, common binding site: fully competitive inhibition, type IA. 20 False competition between S and I for two separate sites that are associated allosterically: pseudocompetitive inhibition, type Ib. 30 A simple graphical test is presented that differentiates between the two types of inhibitor and permits calculation of the four dissociation constants governing the partial reactions of a two-site allosteric model. This test is equally applicable to certain cases of activation: affinity-type activation, type Ib. 40 The usefulness of the proposed test is illustrated using data from the literature, dealing with the effect of phlorizin and phloretin on the D-glucose transport system in brain.
D000495:Allosteric Site / Q000187:drug effects; D000818:Animals; D001667:Binding, Competitive; D001692:Biological Transport / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D004285:Dogs; D004798:Enzymes / Q000378:metabolism; D005947:Glucose / Q000378:metabolism*; D007700:Kinetics; D008954:Models, Biological; D010693:Phloretin / Q000494:pharmacology*; D010695:Phlorhizin / Q000494:pharmacology*
D004798:Enzymes; D010695:Phlorhizin; D005947:Glucose; D010693:Phloretin