Primary structure of histidine decarboxylase

The results of investigation of the primary structure of the Histidine Decarboxylase Micrococcus sp. n. are reported. A comparison of the primary structure of the Histidine Decarboxylase Micrococcus sp. n. with that of the Lactobacillus 30a enzyme suggests the alignment with a 52% identity. It is therefore highly probable that two proteins have evolved from common ancestry. The conservative amino acid sequences with residues (pyruvate, cysteine) of the active center have been found.     

A rapid histidine decarboxylase assay

Histidine decarboxylase (EC 4.1.1.22) catalyzes the conversion of histidine to histamine. Because current assays for enzyme activity are time consuming and require additional enzymes or large amounts of tissue, a rapid radioisotopic assay was devised. Using commercially available radioactive histidine (without additional purification), the enzyme mediates the formation of histamine. The product is resolved from precursor by paper electrophoresis in a formic acid-acetic acid solution for 15 min. After drying and ninhydrin staining, radioactive histamine is measured by liquid seintillation spectrometry. This assay procedure is sensitive enough to measure decarboxylase activity in milligram quantities of rat brain.     

A microassay for mammalian histidine decarboxylase.

This report describes a microassay procedure for mammalian histidine decarboxylase (HDC) based on the measurement of [¹⁴C]O₂ formed from l-[1-¹⁴C]histidine. This assay is particularly useful for quick measurement of HDC activity both in microgram quantities of cell or tissue extract and in tissues that contain significant levels of endogenous histamine.Using this assay, we have shown that the pH optimum, K_m and thermolability of HDC are similar for extracts prepared both from normal rat peritoneal mast cells and from the Furth mouse mastocytoma. HDC activity could be detected in homogenates prepared from 10⁵ rat mast cells, and it was expressed on a per cell basis. Mast cell HDC activity varied with the strain of rat from which the cells were obtained and with the season when they were assayed.     

Spectroscopic analysis of recombinant rat histidine decarboxylase

Mammalian histidine decarboxylases have not been characterized well owing to their low amounts in tissues and instability. We describe here the first spectroscopic characterization of a mammalian histidine decarboxylase, i.e. a recombinant version of the rat enzyme purified from transformed Escherichia coli cultures, with similar kinetic constants to those reported for mammalian histidine decarboxylases purified from native sources. We analyzed the absorption, fluorescence and circular dichroism spectra of the enzyme and its complexes with the substrate and substrate analogues. The pyridoxal-5'-phosphate-enzyme internal Schiff base is mainly in an enolimine tautomeric form, suggesting an apolar environment around the coenzyme. Michaelis complex formation leads to a polarized, ketoenamine form of the Schiff base. After transaldimination, the coenzyme-substrate Schiff base exists mainly as an unprotonated aldimine, like that observed for dopa decarboxylase. However, the coenzyme-substrate Schiff base suffers greater torsion than that observed in other L-amino acid decarboxylases, which may explain the relatively low catalytic efficiency of this enzyme. The active center is more resistant to the formation of substituted aldamines than the prokaryotic homologous enzyme and other L-amino acid decarboxylases. Characterization of the similarities and differences of mammalian histidine decarboxylase with respect to other homologous enzymes would open new perspectives for the development of new and more specific inhibitors with pharmacological potential.     

Mice lacking histidine decarboxylase exhibit abnormal mast cells

Histidine decarboxylase (HDC) synthesizes histamine from histidine in mammals. To evaluate the role of histamine, we generated HDC-deficient mice using a gene targeting method. The mice showed a histamine deficiency and lacked histamine-synthesizing activity from histidine. These HDC-deficient mice are viable and fertile but exhibit a decrease in the numbers of mast cells while the remaining mast cells show an altered morphology and reduced granular content. The amounts of mast cell granular proteases were tremendously reduced. The HDC-deficient mice provide a unique and promising model for studying the role of histamine in a broad range of normal and disease processes.     

Mammalian histidine decarboxylase: from structure to function

Histamine is a multifunctional biogenic amine with relevant roles in intercellular communication, inflammatory processes and highly prevalent pathologies. Histamine biosynthesis depends on a single decarboxylation step, carried out by a PLP-dependent histidine decarboxylase activity (EC 4.1.1.22), an enzyme that still remains to be fully characterized. Nevertheless, during the last few years, important advances have been made in this field, including the generation and validation of the first three-dimensional model of the enzyme, which allows us to revisit previous results and conclusions. This essay provides a comprehensive review of the current knowledge of the structural and functional characteristics of mammalian histidine decarboxylase.     

Reaction of Lactobacillus histidine decarboxylase with L-histidine methyl ester

L-Histidine methyl ester inactivates histidine decarboxylase in a time-dependent manner. The possibility was considered that an irreversible reaction between enzyme and inhibitor occurs [Recsei, P. A., & Snell, E. E. (1970) Biochemistry 9, 1492-1497]. We have confirmed time-dependent inactivation by histidine methyl ester and have investigated the structure of the enzyme-inhibitor complex. Upon exposure to either 8 M guanidinium chloride or 6% trichloroacetic acid, unchanged histidine methyl ester is recovered. Formation of the complex involves Schiff base formation, most likely with the active site pyruvyl residue [Huynh, Q. K., & Snell, E. E. (1986) J. Biol. Chem. 261, 4389-4394], but does not involve additional irreversible covalent interaction between inhibitor and enzyme. Complex formation is a two-step process involving rapidly reversible formation of a loose complex and essentially irreversible formation of a tight complex. For the formation of the tight complex, Ki = 80 nM and koff = 2.5 X 10(-4) min-1. Time-dependent inhibition was also observed with L-histidine ethyl ester, L-histidinamide, and DL-3-amino-4-(4-imidazolyl)-2-butanone. No inactivation was observed with glycine methyl ester or histamine. We propose that in the catalytic reaction the carboxyl group of the substrate is in a hydrophobic region. The unfavorable interaction between the carboxylate group and the hydrophobic region facilitates decarboxylation [Crosby, J., Stone, R., & Liehard, G. E. (1970) J. Am. Chem. Soc. 92, 2891-2900]. With histidine methyl ester this unfavorable interaction is no longer present; hence, there is tight binding.(ABSTRACT TRUNCATED AT 250 WORDS)