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An In Vitro Characterization of γ‐Glutamylhistamine Synthetase: A Novel Enzyme Catalyzing Histamine Metabolism in the Central Nervous System of the Marine Mollusk, Aplysia californica
Author(s) -
Stein Cathy,
Weinreich Daniel
Publication year - 1982
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.1982.tb10873.x
Subject(s) - biochemistry , histamine , biology , glutamine synthetase , glutamate receptor , enzyme , aplysia , glutamine , amino acid , endocrinology , receptor , evolutionary biology
The properties of the histamine metabolizing enzyme, γ‐glutamylhistamine synthetase (γ‐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, γ‐glutamylhistamine (γ‐GHA). γ‐GHA synthetase is a soluble enzyme with an apparent K m of 653 μ m for histamine and 10.6 m m for l ‐glutamate. Synthesis of‐γ‐GHA is energy ‐dependent, having an absolute requirement for ATP. Magnesium ions and di‐thiothreitol are also essential for activity. Of a variety of γ‐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‐γ‐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 <10% of that in ganglia. Differences in substrate specificity and effect of inhibitors distinguish ‐γ‐GHA synthetase from ‐γ‐glutamyl transpeptidase, glutamine synthetase, and carnosine synthetase.