Carnosinase; an enzyme of swine kidney.

Since it was shown in a previous report (1) that certain peptidases were capable of hydrolyzing peptides containing @alanine, the present investigation was undertaken to determine the possible metabolic fate of the naturally occurring peptide, carnosine. Although this substance, /3-alanyl-Lhistidine, has long been known and is one of the most abundant of the non-protein nitrogenous constituents of muscle, little is known regarding its metabolism or function (2). However, in the past few years it has been observed (3) that crude preparations of certain tissues, particularly kidney, spleen, and liver, can hydrolyze carnosine, but this peptide is not split by muscle tissue; nor is the autolysis of muscle affected by the addition of carnosine (4). This work suggests that the first step in the metabolism of carnosine is its hydrolysis into the constituent amino acids. This is also indicated by the work of du Vigneaud, Sifferd, and Irving (5), who found that the histidine of carnosine is available for the growth of animals on a histidine-deficient diet. We have utilized the excellent procedure of Sifferd and du Vigneaud (6) for the synthesis of carnosine. It has been found that certain tissues can hydrolyze this peptide, and we have named the responsible enzyme carnosinase, since its properties are distinct from those of any previously described protease. The carnosinase of hog kidney has been partially purified and has been shown by inhibition and activation studies to be a metalenzyme like other exopeptidases. The specificity of this enzyme has also been studied by its action on synthetic substrates.