COMPARISON OF AMINOPEPTIDASE INHIBITION BY AMINO-ACIDS IN HUMAN AND PORCINE SKELETAL-MUSCLE TISSUES IN-VITRO

We compared the inhibitory action of individual amino acids in vitro o n the activities of alanyl-, arginyl-, leucyl- and pyroglutamyl aminop eptidases purified from human and porcine skeletal muscle tissues. The range of susceptibility to inhibition by individual amino acids (<25 mM) for different aminopeptidase types broadly paralleled that for the respective substrate specificities (in terms of relative rates of hyd rolysis of amino acyl-AMC derivatives) for these enzymes. Thus, alanyl aminopeptidase (which hydrolyses a broad range of aminoacyl-AMC subst rates) was inhibited by a correspondingly broad range of amino acids ( although the respective ranking order of amino acids was not identical in each case), whereas pyroglutamyl aminopeptidase (which hydrolyses only pyroglutamyl AMC as substrate) was inhibited by pyroglutamic acid only. The mode of inhibition (competitive/non-competitive) varied for different enzyme types, both within and between each species. For enz ymes purified from human muscle, alanyl, arginyl and leucyl aminopepti dases were inhibited by amino acids via the non-competitive mode (pyro glutamyl aminopeptidase via the competitive mode), whereas correspondi ng enzymes purified from porcine muscle were inhibited via the competi tive mode. The data obtained indicate that the same aminopeptidase typ es are present in human and porcine skeletal muscle tissues, with corr esponding enzymes having broadly similar assay characteristics and sus ceptibilities to inhibition by amino acids (although the mode of inhib ition for corresponding enzymes may differ in each species). Such data obtained in vitro may prove of value in devising experimental strateg ies to manipulate protein turnover/muscle deposition in vivo, via inhi bition of aminopeptidase action after administration of an appropriate admixture of amino acids. Copyright (C) 1996 Elsevier Science Inc.