Transamination in amino acid metabolism

See also Transamination in Amino Acid Metabolism (from Chapter 20), Citric Acid Cycle Intermediates in Amino Acid Metabolism (from Chapter 21)... 

See also Utilization of Ammonia, Transamination in Amino Acid Metabolism... 

See also Table 5.1, Amino Acids, Genetic Code, Y-Carboxyglutamic Acid, Glutamine, Glutamate as a Precursor of Other Amino Acids (from Chapter 21), Transamination in Amino Acid Metabolism (from Chapter 20), Citric Acid Cycle Intermediates in Amino Acid Metabolism (from Chapter 21), Essential Amino Acids... 

See also Metabolic Nitrogen Balance, Transamination in Amino Acid Metabolism, Amino Acid Degradation, Urea Cycle, Ammonia Transport in the Body, De Novo Pyrimidine Nucleotide Metabolism (from Chapter 22). 

Pyridoxal phosphate is a coenzyme for many enzymes involved in amino acid metabolism, especially in transamination and decarboxylation. It is also the cofactor of glycogen phosphorylase, where the phosphate group is catalytically important. In addition, vitamin Bg is important in steroid hormone action where it removes the hormone-receptor complex from DNA binding, terminating the action of the hormones. In vitamin Bg deficiency, this results in increased sensitivity to the actions of low concentrations of estrogens, androgens, cortisol, and vitamin D. 

The terminology vitamin Bg covers a number of structurally related compounds, including pyridoxal and pyridoxamine and their 5 -phosphates. Pyridoxal 5 -phosphate (PLP), in particular, acts as a coenzyme for a large number of important enzymic reactions, especially those involved in amino acid metabolism. We shall meet some of these in more detail later, e.g. transamination (see Section 15.6) and amino acid decarboxylation (see Section 15.7), but it is worth noting at this point that the biological role of PLP is absolutely dependent upon imine formation and hydrolysis. Vitamin Bg deficiency may lead to anaemia, weakness, eye, mouth, and nose lesions, and neurological changes. 

Pyridoxal phosphate (4) is the most important coenzyme in amino acid metabolism. Its role in transamination reactions is discussed in detail on p. 178. Pyridoxal phosphate is also involved in other reactions involving amino acids, such as decarboxylations and dehydrations. The aldehyde form of pyridoxal phosphate shown here (left) is not generally found in free form. In the absence of substrates, the aldehyde group is covalently bound to the e-amino group of a lysine residue as aldimine ( Schiffs base ). Pyridoxamine phosphate (right) is an intermediate of transamination reactions. It reverts to the aldehyde form by reacting with 2-oxoacids (see p. 178). 

Vitamins, cofactors, and metals have the potential to broaden the scope of antibody catalysis considerably. In addition to hydrolytic and redox reactions, they facilitate many complex functional group interconversions in natural enzymes.131 Pyridoxal, for example, plays a central role in amino acid metabolism. Among the reactions it makes possible are transaminations, decarboxylations, racemizations, and (3,y-eliminations. It is also essential for ethylene biosynthesis. Not surprisingly, then, several groups have sought to incorporate pyridoxal derivatives into antibody combining sites. 

Transamination is of central importance in amino acid metabolism, provid-ingpathwaysforthe catabolism of aU amino acids other than lysine (which does not undergo transamination), although pathways other than transamination may be more important for the catabolism of some amino acids. It also provides a pathway for the synthesis of those amino acids for which there is an alternative source of the oxo-acid (the nonessential amino acids). As can be seen from Table 9.3, many of the oxo-acids are common metabolic intermediates. 

Examples of the sulfhydryl-dependent enzymes include adenyl cyclase and aminotransferases. Adenyl cyclase catalyzes the conversion of ATP to cyclic AMP needed in brain neurotransmission. Aminotransferases are involved in transamination and thus important in amino acid metabolism. 

Two types of reactions play prominent roles in amino acid metabolism. In transamination reactions, new amino acids are produced when a-amino groups are transferred from donor a-amino acids to acceptor a-keto acids. Because transamination reactions are reversible, they play an important role in both amino acid synthesis and degradation. Ammonium ions or the amide nitrogen of glutamine can also be directly incorporated into amino acids and eventually other metabolites. 

Decarboxylation and transamination proceed via the intermediacy of an amino acid-pyridoxal phosphate complex. Pyridoxal phosphate is related to vitamin Be and is of pivotal importance in amino acid metabolism. This cofactor occurs in two forms pyridoxal-5 -phosphate (aldehyde form) and pyridoxamine (amine form), which mediate a reversible interconversion of a-amino acid and a-keto acids via a Schiff-... 

Vitamin is pyridoxal (ll.lOSf), pyridoxine (ll.lOSg) or pyridoxamine (ll.lOSh), all of which exist as their phosphate esters. This vitamin was first isolated in 1936. Pyridoxyl phosphate (ll.lOSi) is a versatile coenzyme used by all living organisms which participates in transamination (11.111) and (11.112), decarboxylation (11.113) and racemisation (11.114) reactions. It is the essential cofactor in amino acid metabolism. Virtually all enzymes which catalyse reactions of 2-amino acids utilise pyridoxyl phosphate as the coenzyme (11.111) through (11.114). 

Thus, we see that transaminases perform two vital functions in amino acid metabolism. By taking part in the biosynthesis of nonessential amino acids, they provide a means to help readjust the relative proportions of amino acids to meet the particular needs of the body. This is a vital function because most of our diets do not contain amino acids in the exact proportions the body requires. Also, as we noted in Section 24.9, transamination reactions allow the nitrogen atoms of all amino acids to be transferred to a-keto acids to form glutamate and aspartate when disposal of nitrogen is necessary. 

In spite of the failure, to date, to isolate and adequately characterise more than two transaminases, both of which catalyse -amino group transfer, it is now generally accepted that transamination plays an important part in amino acid metabolism. 

Intracellular PLP, which is derived from extracellular PL, functions as a very versatile coenzyme. Various reactions in amino acid metabolism, including transaminations, a decarboxylations, a,P eliminations, P,y eliminations, aldolizations, and racemizations, are PLP dependent. 

Vitamin Bg has a central role in amino acid metabolism as the coenzyme for a variety of reactions, including transamination and decarboxylation. It is also the coenzyme of glycogen phosphorylase and acts to modulate the activity of steroid and other hormones (including retinoids and vitamin D) that act by regulation of gene expression. 

Transamination is of central importance in amino acid metabolism, providing pathways for catabolism of most amino acids as well as the synthesis of those amino acids for which there is a source of the oxo-acid other than from the amino acid itself—the nonessential amino acids. 

The transamination reaction is important biologically in amino acid metabolism. Simple aldehydes are rare in biological systems and are mostly masked as imines. Biochemists often refer to them as Schiff bases, which are a special class of aldehyde imine where the nitrogen atom is substituted by an alkyl or aryl group. The transamination reaction interconverts amino and carbonyl functionalities (Figure 14.32). The enzymes involved in the process are called transaminases, and they require pyridoxal phosphate as a cofactor. 

Pyridoxal phosphate mainly serves as coenzyme in the amino acid metabolism and is covalently bound to its enzyme via a Schiff base. In the enzymatic reaction, the amino group of the substrate and the aldehyde group of PLP form a Schiff base, too. The subsequent reactions can take place at the a-, (3-, or y-carbon of the respective substrate. Common types of reactions are decarboxylations (formation of biogenic amines), transaminations (transfer of the amino nitrogen of one amino acid to the keto analog of another amino acid), and eliminations. 

Be Pyridoxine, pyridoxal, pyridoxamine Coenzyme in transamination and decarboxylation of amino acids and glycogen phosphorylase role in steroid hormone action Disorders of amino acid metabolism, convulsions... 

The nitrogen contained in the amino acids is usually disposed of through the urea cycle. One of the early, if not the first, steps in amino acid catabolism involves a transamination using oxaloacetate or a-ketoglutarate as the amino-group acceptor. This converts the amino acid into a 2-keto acid, which can then be metabolized further. 

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