Carnosine-synthetase inhibition of beta-alanine analogues

A number of beta-alanine analogues were tested for their ability to inhibit carnosine-synthetase from rat and chick skeletal muscle. Of the analogues tested, 3-aminopropane-sulfonic acid (APS) was the most effective inhibitor of enzyme from either source. 5-Aminovaleric acid (5-AV) also inhibited the enzyme from rat, but did not inhibit the enzyme from chick. 2-Aminoethylphosphonic acid and o-phosphoethanolamine had a small amount of inhibitory activity on both rat and chick enzymes, while 3-aminopropanephosphonic acid, aminooxyacetic acid and nipecotic acid had a small amount of inhibitory activity on the rat enzyme only. None of the analogues tested acted as substrates for either enzyme under our conditions. Kinetic data indicated that the inhibition by APS was competitive with respect to beta-alanine for both rat and chick enzymes. Inhibition of the rat enzyme by 5-AV was non-competitive with respect to beta-alanine for both rat and chick enzymes. Inhibition of the rat enzyme by 5-AV was noncompetitive with respect to beta-alanine. APS and 5-AV were also shown to inhibit carnosine-synthetase from rat brain and heart. Chronic injections of either APS or 5-AV failed to produce significant changes in carnosine levels in rat skeletal muscle or brain; however preliminary results indicate that APS injections may produce a lowering of carnosine levels in rat heart.