An in vitro characterization of gamma-glutamylhistamine synthetase: a novel enzyme catalyzing histamine metabolism in the central nervous system of the marine mollusk, Aplysia californica.
The properties of the histamine metabolizing enzyme, gamma-glutamylhistamine synthetase (gamma-GHA synthetase) were studied in Aplysia ganglia in vitro. This enzyme catalyzes the incorporation of histamine into peptide linkage with L-glutamate to form a peptidoamine, gamma-glutamylhistamine (gamma-GHA). gamma-GHA synthetase is a soluble enzyme with an apparent Km of 653 microM for histamine and 10.6 mM for L-glutamate. Synthesis of gamma-GHA is energy-dependent, having an absolute requirement for ATP. Magnesium ions and dithiothreitol are also essential for activity. Of a variety of gamma-glutamyl compounds and glutamate analogs tested, only L-glutamate was effectively incorporated into peptide linkage with histamine. Similarly, the enzyme has a higher affinity for histamine than for numerous imidazole analogs. In addition, 3,4-dihydroxyphenylethylamine (dopamine), 5-hydroxytryptamine, octopamine, and several other amines tested are effective inhibitors of gamma-GHA synthesis. Ganglia, nerve trunks, and the capsule surrounding the ganglion had the highest synthetase activity. The specific activity of the enzyme in muscle, heart, and hemolymph was less than 10% of that in ganglia. Differences in substrate specificity and effect of inhibitors distinguish gamma-GHA synthetase from gamma-glutamyl transpeptidase, glutamine synthetase, and carnosine synthetase.
D000588:Amines / Q000494:pharmacology; D000596:Amino Acids / Q000494:pharmacology; D001048:Aplysia / Q000201:enzymology*; D005974:Glutamate-Ammonia Ligase / Q000378:metabolism; D006632:Histamine / Q000031:analogs & derivatives / Q000096:biosynthesis / Q000378:metabolism*; D010453:Peptide Synthases / Q000378:metabolism*; D011970:Receptors, Histamine H2 / Q000378:metabolism; D013329:Structure-Activity Relationship; D014018:Tissue Distribution; D005723:gamma-Glutamyltransferase / Q000378:metabolism
D000588:Amines; D000596:Amino Acids; D011970:Receptors, Histamine H2; C013541:gamma-glutamylhistamine; D006632:Histamine; D005723:gamma-Glutamyltransferase; D005974:Glutamate-Ammonia Ligase; D010453:Peptide Synthases; C035550:gamma-glutamylhistamine synthetase; C019844:carnosine synthetase