L-tryptophan. A non-allosteric organ-specific uncompetitive inhibitor of human placental alkaline phosphatase.
l-Tryptophan, but not d-tryptophan, inhibits human placental and intestinal alkaline phosphatases, but not those of liver and bone. The nature of this stereospecific organ-specific inhibition has been elucidated. Thus, from a study of the effect of substrate concentration on inhibition in which double-reciprocal plots of 1/v versus 1/s at various inhibitor concentrations were made, this inhibition is judged to be ;uncompetitive'. That the inhibition is non-allosteric is an opinion based on (1) hyperbolic curves obtained from plotting the percentage inhibition against inhibitor concentration; (2) the independence of the inhibition to heat denaturation and urea treatment; (3) the relatively low value of entropy change; and (4) a value close to unity for n, the number of l-tryptophan molecules that combine with one molecule of enzyme. Finally, a homosteric mechanism is further postulated for the inhibition by l-tryptophan based on the increase of optimum temperature for maximum velocity and the decrease of this inhibition with increasing temperature. The mechanism of this inhibition is discussed.
D000469:Alkaline Phosphatase / Q000037:antagonists & inhibitors*; D001665:Binding Sites; D001842:Bone and Bones / Q000201:enzymology; D005260:Female; D006358:Hot Temperature; D006801:Humans; D007422:Intestines / Q000201:enzymology; D007700:Kinetics; D008099:Liver / Q000201:enzymology; D009928:Organ Specificity; D010920:Placenta / Q000201:enzymology*; D011247:Pregnancy; D011489:Protein Denaturation; D013237:Stereoisomerism; D013816:Thermodynamics; D014364:Tryptophan / Q000494:pharmacology*; D014508:Urea
D014364:Tryptophan; D014508:Urea; D000469:Alkaline Phosphatase