Histidine decarboxylated product

Most people have heard of antihistamines, even if they have little concept of the nature of histamine. Histamine is the decarboxylation product from histidine, and is formed from the amino acid by the action of the enzyme histidine decarboxylase. The mechanism of this pyridoxal phosphate-dependent reaction will be studied in more detail later (see Section 15.7). 

Dopamine is the decarboxylation product of DOPA, dihydroxyphenylalanine, and is formed in a reaction catalysed by DOPA decarboxylase. This enzyme is sometimes referred to as aromatic amino acid decarboxylase, since it is relatively non-specific in its action and can catalyse decarboxylation of other aromatic amino acids, e.g. tryptophan and histidine. DOPA is itself derived by aromatic hydroxylation of tyrosine, using tetrahydrobiopterin (a pteridine derivative see Section 11.9.2) as cofactor. 

Histamine (Figure 6.110) is the decarboxylation product from histidine and is often involved in human allergic responses, e.g. to insect bites or pollens. Stress stimulates the action of the enzyme histidine decarboxylase and histamine is released from mast cells (Figure 6.110). Topical antihistamine creams are valuable for pain relief, and oral antihistamines are widely prescribed for nasal allergies such as hay-fever. Major effects of histamine include dilation of blood vessels, inflammation and swelling of tissues, and narrowing of airways. In serious cases, life-threatening anaphylactic shock may occur, caused by a dramatic fall in in blood pressure. 

Decarboxylation, or loss of the a-carboxyl group as C02, is another reaction common to most amino acids. It, too, requires pyridoxal phosphate as a coenzyme. Decarboxylation reactions are irreversible. For example, see Figure 20.5, which shows the decarboxylation of histidine to produce histamine. Table 20.6 lists transamination and decarboxylation products of some representative amino acids. 

Opuntiaficus-indica (Cactaceae), Spinacia oleracea (Chenopodiaceae), Drosera spp. (Droseraceae), Senna obtusfolia (Fabaceae), Musa sapientam (banana) (Musaceae), Nepenthes spp. (Nepenthaceae), Sarracenia sp. (Sarraceniaceae), Urtica dioica (Urticaceae) animals decarboxylation product of Histidine... 

The activity of histidine decarboxylase preparations can be measured by determining either of the decarboxylation products of histidine, i.e. histamine or carbon dioxide. Most of the methods are in vitro techniques using organ slices, minces or cell-free extracts, and they have the usual limitations of in vitro measurements - - . In vivo methods have also been used, but these give information primarily about the decarboxylation of histidine in the body as a whole rather than about the distribution of the enzyme in specific organs. 

The use of tissue slices for experiments on histidine decarboxylation introduces the additional problem of the access of substrate, co-enzyme and inhibitors into the cells. In this connection, it should be noted that in practice the specificity of an enzyme within a cell may be increased by the specificity of the substrate-transporting system. Similar considerations apply to the in vivo inhibition of histidine decarboxylases there is, however, the additional possibility of modifying production of the apo-enzyme either by restricting the supply of amino acids or by altering the hormonal state of the animal. 

INHIBITION OF HISTIDINE DECARBOXYLATION ttt ffWO The in vivo production of histamine, and of other amines, in rats can be diminished by the use of pyridoxine-deficient diets, pyridoxine antagonists, or non-specific inhibitors such as semicarbazide > i >i . In female rats receiving a pyridoxine-deficient, histamine-free diet, the urinary output of histamine was reduced to about 50% of normal simultaneous administration of semicarbazide further reduced the histamine output to about 20% of normal. However, the histamine content of the tissues of these animals did not differ significantly from those of controls, except in the stomach where the histamine content dropped to a few per cent of normal. 

Glycine and glutamate are amino acids that serve directly as neurotransmitters are. y-Aminobutyric acid (GABA), the decarboxylation product of glutamate, is also a neurotransmitter. Amino acid metabolites that function in neurotransmission include histamine (from histidine), serotonin (from tryptophan), and catecholamines (epinephrine, dopamine, and norepinephrine), which are derived from tyrosine. 

The imidazole molecule is incorporated into many biologically relevant molecules. For example, the amino acid histidine is present in proteins and enzymes, while histamine (its decarboxylated product) is important in the body s immune response system. The imidazole ring has been found in a number of natural products, particularly the oroidin-derived alkaloids. One of the structurally simple compounds in this class of natural products is girolline, containing a 2-amino-imidazole attached to a chlorohydrin moiety. ... 

Mammalian Amino Add Decarboxylases. Amino acid decarboxylases occur in many animal tissues. Histidine decarboxylase of kidney has a pH optimum near 9. The decarboxylation product, histamine, has very powerful pharmacological effects in animals, and its formation in minute quantities has been measured pharmacologically. This nonspecific type of assay has also been used to detect histidine decarboxylase in other tissues. More specific assays have recently shown this enzyme to occur in mast cells, in which histamine accumulates the stored histamine is released by rupture of these fragile cells. 

Histamine production. Growing cultures of P. acnes produce histamine (Allaker et al., 1986) and its synthesis increases with increasing growth rate. The growth of P. acnes is optimal at pH 6.0, while histamine synthesis has two pH-optima of 4.5 and 7.5. Histamine is formed as a result of histidine decarboxylation. 

Amine build-up in fish muscle usually results from decarboxylation of amino acids in the muscle by enzymes of bacterial origin. This review will present information on the activity of bacterial decarboxylases and the formation of amines in fish. Mechanisms of decarboxylase action and production of bacterial decarboxylases in fish muscle are discussed. Emphasis is placed upon studies dealing with formation of histidine decarboxylase and histamine. Histamine, because of its involvement in Scombroid food poisoning, has been extensively studied with regard to its formation in fish and fishery products. 

Because amine formation in fish muscle and other foods usually results from bacterial growth with concomitant production of a bacterial decarboxylase, this paper will concentrate on the mechanisms of bacterial decarboxylation and factors influencing the production and activity of the enzymes. Also, because of the overall scope of the subject, the availability of excellent reviews on bacterial decarboxylation (2, 3) and the public health importance of histamine in fish and fishery products, this paper will primarily be limited to a discussion of histidine decarboxylase (EC 4.1.1.22) and the formation of histamine in fish muscle. 

This group of alkaloids is an exception in the transformation process of structures, because the imidazole nucleus is already made at the stage of the precursor. The a of these alkaloids is L-histidine, and the first A is developed in a decarboxylation process by histidine decarboxylase (HDC). The histamine is a product of... 

Nevertheless, malonyl-CoA is a major metabolite. It is an intermediate in fatty acid synthesis (see Fig. 17-12) and is formed in the peroxisomal P oxidation of odd chain-length dicarboxylic acids.703 Excess malonyl-CoA is decarboxylated in peroxisomes, and lack of the decarboxylase enzyme in mammals causes the lethal malonic aciduria.703 Some propionyl-CoA may also be metabolized by this pathway. The modified P oxidation sequence indicated on the left side of Fig. 17-3 is used in green plants and in many microorganisms. 3-Hydroxypropionyl-CoA is hydrolyzed to free P-hydroxypropionate, which is then oxidized to malonic semialdehyde and converted to acetyl-CoA by reactions that have not been completely described. Another possible pathway of propionate metabolism is the direct conversion to pyruvate via a oxidation into lactate, a mechanism that may be employed by some bacteria. Another route to lactate is through addition of water to acrylyl-CoA, the product of step a of Fig. 17-3. Tire water molecule adds in the "wrong way," the OH ion going to the a carbon instead of the P (Eq. 17-8). An enzyme with an active site similar to that of histidine ammonia-lyase (Eq. 14-48) could... 

Other products from histidine include the hormonal substance histamine formed by decarboxylation, the oxidation product, imidazole acetic acid, and N5- and A/c-methylhistidines. Histamine plays a role in release of gastric secretions and allergic responses (Chapter 5). Drugs (antihistamines) that inhibit its release are in widespread use. The unusual amino acid diphthamide has an unknown function in pro-... 

Alanine and aspartic acid are produced commercially utilizing enzymes. In the case of alanine, the process of decarboxylation of aspartic acid by the aspartate decarboxylase from Pseudomonas dacunhae is commercialized. The annual world production of alanine is about 200 tons. Aspartic acid is produced commercially by condensing fumarate and ammonia using aspartase from Escherichia coli. This process has been made more convenient with an enzyme immobilization technique. Aspartic acid is used primarily as a raw material with phenylalanine to produce aspartame, a noncaloric sweetener. Production and sales of aspartame have increased rapidly since its introduction in 1981. Tyrosine, valine, leucine, isoleucine, serine, threonine, arginine, glutamine, proline, histidine, cit-rulline, L-dopa, homoserine, ornithine, cysteine, tryptophan, and phenylalanine also can be produced by enzymatic methods. 

The assay described for amino acid decarboxylase can be used to quantitate the substrates and products associated with the decarboxylation of arginine, aspartate, 2,6-diaminopimelate, histidine, glutamate, lysine, and ornithine. 

Histamine, an amine produced in numerous tissues throughout the body, has complex physiological effects. It is a mediator of allergic and inflammatory reactions, a stimulator of gastric acid production, and a neurotransmitter in several areas of the brain. Histamine is formed by the decarboxylation of L-hisddine in a reaction catalyzed by histidine decarboxylase, a pyridoxal phosphate-requiring enzyme. 

The decarboxylation of histidine at any particular site depends on the presence of appropriate amounts of substrate, co-enzyme and apo-enzyme. Any interference with the supply or functioning of these components could lead to inhibition of histamine production. 

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