Peptide inhibition of mammalian histidine decarboxylase.

The hypothesis that N-terminal histidine peptides might act as inhibitors to histidine decarboxylase was investigated. A murine mastocytoma was utilized as enzyme source. The crude extract of this tissue exhibits high rates of decarboxylation of both histidine and DOPA and was used to establish the specificity in the effect of the compounds tested. For kinetic analyses a highly purified histidine decarboxylase fraction was used. The effect of some representative peptides on both enzyme activities were recorded. Histidine decarboxylase exclusively was inhibited by N-terminal histidine peptides. None of the other peptides investigated interfered negatively with this enzyme. This inhibition was consistent in the purified preparation and appeared to be more pronounced with increasing hydrophobicity in the second amino acid. Histidyl-phenylalanine was found to be about 100-fold as potent as the commonly used specific histidine decarboxylase inhibitor alpha-methyl histidine. It is concluded that small peptides with histidine as the N-terminal amino acid might act as specific inhibitors for mammalian histidine decarboxylase. An analog effect of small tyrosyl or phenylalanyl peptides was not seen for the DOPA decarboxylase.