Amino acid decarboxylases animal

The formation of amines corresponding to certain amino acids has been known for a century, and for over 50 years it has been known that certain amino acids can be decarboxylated by animal and microbial preparations. Hanke and Koessler found that various strains of E. colt contained decarboxylases for different amino acids, and that the ability to decarboxylate individual amino acids was so distributed among strains as to indicate that specific enzymes existed for the decarboxylation of each of the susceptible amino acids. The reactions of amino acid decarboxylases are illustrated in Fig. 31. 

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. 

In animals, decarboxylation of glutamic acid, histidine, tyrosine, phenylalanine and tryptophane and hydroxy derivatives of the aromatic amino acids is reasonably well established. The enzymes catalysing decarboxylation of glutamic acid and of histidine are substrate specific but there is no certain evidence for the existence of specific aromatic amino acid decarboxylases. 

Most alkaloids are derived from amino acids (Fig. 3) and the first reaction in the otherwise independent pathways is the decarboxylation of the respective amino acid by an amino acid decarboxylase (AADC) (Figs. 1 and 3) this step is often under complex regulation. Plant and animal AADCs share high amino acid identity, with significant similarities in subunit structure and kinetic characteristics. In contrast to their mammahan and insect counterparts, plant AADCs exhibit high specificity for their respective substrates. The reaction is pyridoxal-5 -phosphate (PLP)-dependent. 

In many cases, the site of action of a metabolite antagonist is known. Thus pyrithiamine displaces thiamine from the enzyme which phosphoryl-ates it to give the coenzyme. Again, desoxypyridoxine [(p.j), R = - CH3] seems inactive until it is phosphorylated in animals to a derivative which competes with pyridoxal phosphate, which is the coenzyme of the amino-acid decarboxylases (Woolley, 1952). 

Drosophila DDC belongs to a family of pyridoxal-dependent decarboxylases that extends from prokaryotes to eukaryotic plants and animals. The members of this family show significant sequence similarity over much of their length, even though the individual proteins have quite different substrate specificities, including the amino acids tyrosine, tryptophan, phenylalanine, histidine, and glutamate, and the amino acid derivatives... 

In addition to resolution approaches, there are three main methods to prepare amino acids by biological methods addition of ammonia to an unsaturated carboxylic acid the conversion of an a-keto acid to an amino acid by transamination from another amino acid, and the reductive animation of an a-keto acid. These approaches are discussed in Chapter 19 and will not be discussed here to avoid duplication. The use of a lyase to prepare L-aspartic acid is included in this chapter as is the use of decarboxylases to access D-glutamic acid. 

Table 7.2 Sequence alignment (amino acids) of ornithine decarboxylase (ODC) of selected taxa from plants, animals, fungi and bacteria. Conserved sites are marked by x ...

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. 

Because of the numerous enzymes requiring pyridoxal phosphate, a large variety of biochemical lesions are associated with vitamin B5 deficiency. These lesions are concerned primarily with amino acid metabolism, and a deficiency affects the animal s growth rate. Convulsions may also occur, possibly because a reduction in the activity of glutamic acid decarboxylase results in an accumulation of glutamic acid. In addition, pigs reduce their food intake and may develop anaemia. Chicks on a deficient diet show jerky movements in adult birds, hatchability and egg production are adversely affected. In practice, vitamin B5 deficiency is unlikely to occur in farm animals because of the vitamin s wide distribution. 

The conversion of pyridoxal to pyridoxamine in heat-sterilized media was confirmed to be due to the reaction of pyridoxal with amino acids (Snell 1945). This was the first discovery of nonenzymatic transamination. The transamination reaction in animal tissues was first discovered in 1937 by Alexander Braunstein and associates as an amino group transfer between glutamate and alanine in pigeon muscle extract (Braunstein 1939). Irwin Gunsalus and associates showed that the tyrosine decarboxylase activity of S. faecalis was... 

The animal decarboxylases differ from the bacterial ones in having a lower quotient of activity 6i, iio) pjj optimum in the alkaline instead of the acid Amino-acid... 

The carboxylases have for their coenzyme pyridoxal phosphate which acts according to the mechanism described on p. 174. A whole series of decarboxylases exists, each being specific for the L-form of a given amino add. Certain of them have been isolated from animal tissues such as liver and kidney, but the majority have been isolated from micro-organisms in which the enzymes appear if their specific substrate is present in the culture medium. In micro-organisms therefore these decarboxylases are adaptive enzymes. The amines produced by the decarboxylation of amino acids (Table XIII) often possess pharmacological activity this is the case for histamine, the product of the decarboxylation of histidine. 

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