MetaCyc Enzyme: γ-glutamylhistamine synthetase

Species: Aplysia californica

This enzyme has been characterized in extracts of ganglia from the marine mollusk Aplysia californica [Stein82]. Its cellular distribution in neuronal cell types was determined by activity assays. Activity was found in C2 cells and all other single nerve cell bodies tested. The results supported the hypothesis that γ-glutamylation by this enzyme functions in the inactivation of neuronally released histamine [Stein83].

The enzyme was primarily found in ganglia and nerve trunks of nerve tissue and in the connective tissue sheath surrounding the ganglion. Relatively low amounts of activity were found in aorta, heart, buccal muscle and hemolymph [Stein82].

Locations: cytosol

Gene-Reaction Schematic

Gene-Reaction Schematic

GO Terms:
Cellular Component:
GO:0005829 - cytosol [Stein82]

Created 26-Mar-2009 by Fulcher CA, SRI International

Enzymatic reaction of: γ-glutamylhistamine synthetase

Inferred from experiment

Synonyms: γ-glutamylhistamine synthase, γ-GHA synthetase, L-glutamate:histamine ligase

EC Number:

histamine + L-glutamate + ATP → N-α-γ-L-glutamylhistamine + ADP + phosphate + H+

The direction shown, i.e. which substrates are on the left and right sides, is in accordance with the direction in which it was curated.

The reaction is physiologically favored in the direction shown.

The enzyme was assayed by measuring the incorporation of 14C histamine into 14C N-α-γ-L-glutamylhistamine and identification of the product by micro-column ion-exchange chromatography, high-voltage paper electrophoresis, thin-layer chromatography and HPLC [Stein82].

Maximal in vitro synthesis of N-α-γ-L-glutamylhistamine required L-glutamate, ATP, L-dithiothreitol and Mg2+ [Stein82].

Cofactors or Prosthetic Groups: Mg2+ [Stein82]

Activators (Allosteric): serotonin [Stein82] Inhibitors (Unknown Mechanism): octopamine [Stein82], (R)-noradrenaline [Stein82], dopamine [Stein82], N-acetyl-serotonin [Stein82], tyramine [Stein82], 4-methylhistamine [Stein82], 2-methylhistamine [Stein82], 2-pyridylethylamine [Stein82], butylamine [Stein82]Kinetic Parameters:
Substrate Km (μM) Citations
L-glutamate 10600.0 [Stein82]
histamine 653.0 [Stein82]

T(opt): 41 °C [Stein82]

pH(opt): 8 [Stein82]


Stein82: Stein C, Weinreich D (1982). "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." J Neurochem 38(1);204-14. PMID: 6125565

Stein83: Stein C, Weinreich D (1983). "Metabolism of histamine in the CNS of Aplysia californica: cellular distribution of gamma-glutamylhistamine synthetase." Comp Biochem Physiol C 74(1);79-83. PMID: 6132775

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Please cite the following article in publications resulting from the use of MetaCyc: Caspi et al, Nucleic Acids Research 42:D459-D471 2014
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