Histidine decarboxylase function

Ohtsu, H. Watanabe, T. (2003). New functions of histamine found in histidine decarboxylase gene knockout mice. Biochem. Biophys. Res. Commun. 305, 443-7. 

Inhibition by Inactivation or Displacement of the Co-enzyme The function of pyridoxal phosphate as the co-enzyme of histidine decarboxylase depends on the ability of the aldehyde group to react with the a-amino group of histidine. However, the aldehyde group also reacts with a wide variety of amino acids, amines and carbonyl reagents. The specificity of the holo-enzyme-substrate interaction is therefore due to the apo-enzyme. The co-enzyme attached to the active centre is presumably in equilibrium with free co-enzyme in the surrounding solution. 

Merely to state that the physiological function of the histidine decarboxylases is the conversion of histidine to histamine is to evade the problem of the function of histamine itself. A compromise will therefore be adopted so that due aecount can be taken of the ways in which the search for possible roles for histamine in physiological processes has shed light on the function of the enzymes by which histamine is formed. 

The first question to arise is whether the two main classes of mammalian histidine decarboxylase, the specific and non-specific enzymes, are of equal importance in relation to the physiological function of histamine. Consideration of the values of the Michaelis eonstant, approximately 10 m for the specific, and 10 % for the non-specific, enzyme Table 4.6), indicates that the specific histidine decarboxylase has the greater affinity for histidine. This might be taken to imply that the specific enzyme is the more important source of histamine in the body . 

Such considerations do not, however, exclude the participation of the nonspecific enzyme as a source of body histamine. The non-specific histidine decarboxylase of guinea-pig kidney is known to have a high affinity for DOPA and 5-HTP, but a low affinity for histidine and phenylalanine . At first sight, then, it would appear that this enzyme is more likely to produce dopamine and 5-hydroxytryptamine than to form histamine or / -phenyl-ethylamine. It must be remembered, however, that the substrates DOPA and 5-HTP are not normally detectable in blood or tissues, while histidine and phenylalanine are present in amounts which compensate for the low affinity of the enzyme for these two amino acids. In terms of the capacity to form the corresponding amines, therefore, there is no reason to suppose that the decarboxylation of histidine is a less important function of the non-specific enzyme than is the decarboxylation of its other substrates. 

The above considerations emphasize that the rate at which histamine is formed by a tissue is of greater significance than the amount of histamine actually present in that tissue. Thus, the determination of histidine decarboxylase activity represents a dynamic approach to the elucidation of the physiological function of histamine, in contrast to the earlier static approach based on measurements of the histamine content of tissues . 

The specific histidine decarboxylase of mast cells apparently produces histamine for local storage within the mast cell itself. This may be the primary function of the mast celP . 

The function of the non-specific histidine decarboxylase of rabbit- or guinea-pig liver and kidney remains to be clarified. However, in view of its wide substrate specificity [Table 4.3), this enzyme may rather be a general aromatic L-amino acid decarboxylase, the purpose of which is to produce other physiologically important amines in addition to histamine. 

Pyruvyl-dependent amino acid decarboxylases are mechanistically analogous to the PLP-dependent amino acid decarboxylases wherein a pyruvyl group in amido linkage to the amino terminus of the protein functions in place of PLP. The formation of a Schiff base linkage between the a-amino function of the amino acid and the ketonic carbonyl of the pyruvyl moiety is supported by the results of borohydride trapping experiments with L-histidine decarboxylase Lactobacillus 30a) in the presence of substrate (265). Evidence could not be found for a reducible internal aldimine in the absence of substrate. 

De las Rivas, B., Rodriguez, H., Carrascosa, A. V., Munoz, R. (2008). Molecular cloning and functional characterization of a histidine decarboxylase from Staphylococcus capitis. Journal of Applied Microbiology, 104, 194—203. http //dx.doi.org/10.llll/ J.1365-2672.2007.03549.X. 

Rashkovetskii, L. G., Prozorovskii, V. N. (1983). Kinetic properties and functional role of domains of Micrococcus sp.n histidine decarboxylase. Biokhimiia, 48, 297-304. 

Hepatitis 12 Histaminase 19, 20 Histamine human brain 60 kidney function, 74, 80 localization 4, 5 metabolism 17, 19 microcirculation 84 ff, 86 occurrence 49 ff pharmacology 70, 71 production 8 respiratory metabolism 89 turnover 23, 24 Histamine headache 126 Histamine-A-methyltransferase 17 Histidine decarboxylase 2, 7 Homoprotocatechuic acid see 3,4-Dihy-droxyphenylacetic acid Homovanillic acid see 3-Methoxy-4-hy-droxyphenylacetic acid 5-Hydroxindole acetic acid excretion 11, 12 microcirculation 86 occurrence 46 ff... 

The ECL cells comprise approximately one-third of the endocrine cells in the oxyntic (acid-secreting) mucosa of most vertebrates. They are small, 8- to 10-pmdiameter cells that contain numerous electron-translucent cytoplasmic vesicles, many of which have an electron-dense core. ECL cells store histanrrine and contain histidine decarboxylase (HDC), the enzyme required for histamine synthesis. The obvious role of the ECL cells is to release histamine, which acts as a paracrine agent to stimulate the parietal cells. It has been demonstrated that the vesicles contain other regulatory compounds, such as chronxigranin and pancreastatin, but neither the specific compounds nor their functional significance has been defined. 

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