Transamination transfer

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. 

How are the other amino acids deaminated Most are transaminated, transferring their N to make glutamate ... 

In transamination an amine group is transferred from L glutamic acid to pyruvic acid An outline of the mechanism of transamination is presented m Figure 27 4... 

Step 1 of Figure 29.14 Transimination The first step in transamination is trans-imination—the reaction of the PLP—enzyme imine with an a-amino acid to give a PLP—amino acid imine plus expelled enzyme as the leaving group. The reaction occurs by nucleophilic addition of the amino acid -NH2 group to the C=N bond of the PLP imine, much as an amine adds to the C=0 bond of a ketone or aldehyde in a nucleophilic addition reaction (Section 19.8). The pro-tonated diamine intermediate undergoes a proton transfer and expels the lysine amino group in the enzyme to complete the step. 

The rest of the amino acids are synthesized by transamination reactions in which the amino group resident on one amino acid, such as glutamic acid, is transferred onto the ketone group of another molecule as shown in the following example ... 

Transamination The reaction in which an amine group is transferred from an amino acid to a carboxylic acid, thereby creating a new amino acid. 

Transamination is a process in which the oNHa group of an amino acid is removed and the oxoacid is formed. However, the a-NHj group is not lost it is transferred to the oxoacid of another amino acid ... 

For some reactions, the process of transamination is near-equilibrium. This means that amino acids involved can be synthesised from their oxoacid by transfer of the a-NHa group. There are five amino acids in this group ... 

Figure 8.17 The metabolism of branched-chain amino acids in muscle and the fate of the nitrogen and oxoacids. The a-NH2 group is transferred to form glutamate which is then aminated to form glutamine. The ammonia required for aminab on arises from glutamate via glutamate dehydrogenase, but originally from the transamination of the branded chain amino acids. Hence, they provide both nitrogen atoms for glutamine formation.

Figure 9.5 A summary of pathways of the three main fueb and the positions where they enter the cycle. The figure also shows the release of hydrogen atoms/electrons and their transfer into the electron transfer chain for generation of ATP and formation of water. Glutamine is converted to glutamate by deamidation and glutamate is converted to oxoglutarate by transamination or deamination. The process of glycolysis also generates ATP as shown in the Figure.

GABA acts as an inhibitory transmitter in many different CNS pathways. It is subsequently destroyed by a transamination reaction (see Section 15.6) in which the amino group is transferred to 2-oxoglutaric acid, giving glutaric acid and succinic semialdehyde. This also requires PLP as a cofactor. Oxidation of the aldehyde group produces succinic acid, a Krebs cycle intermediate. 

Among the NH2 transfer reactions, transaminations (1) are particularly important. They are catalyzed by transaminases, and occur in both catabolic and anabolic amino acid metabolism. During transamination, the amino group of an amino acid (amino acid 1) is transferred to a 2-oxoacid (oxoacid 2). From the amino acid, this produces a 2-oxo-acid (a), while from the original oxoacid, an amino acid is formed (b). The NH2 group is temporarily taken over by enzyme-bound pyridoxal phosphate (PLP see p. 106), which thus becomes pyridoxamine phosphate. 

In the malate shuttle (left)—which operates in the heart, liver, and kidneys, for example-oxaloacetic acid is reduced to malate by malate dehydrogenase (MDH, [2a]) with the help of NADH+HT In antiport for 2-oxogluta-rate, malate is transferred to the matrix, where the mitochondrial isoenzyme for MDH [2b] regenerates oxaloacetic acid and NADH+HT The latter is reoxidized by complex I of the respiratory chain, while oxaloacetic acid, for which a transporter is not available in the inner membrane, is first transaminated to aspartate by aspartate aminotransferase (AST, [3a]). Aspartate leaves the matrix again, and in the cytoplasm once again supplies oxalo-acetate for step [2a] and glutamate for return transport into the matrix [3b]. On balance, only NADH+H"" is moved from the cytoplasm into the matrix ATP is not needed for this. 

In these transamination reactions, the amino group from the amino acid is transferred to a-ketoglutarate to form glutamate and the corresponding a-keto acid. 

Figure 9-1. Molecular interconversions in handling of ammonia. The major enzyme responsible for interconversion of glutamate and a-ketoglutarate is glutamate dehydrogenase. No free ammonia is ever present during direct transfer of amino groups from alanine or aspartate via transamination to produce glutamate. ALT, alanine aminotransferase AST, aspartate aminotransferase.

FIGURE 18-4 Enzyme-catalyzed transaminations. In many aminotransferase reactions, a-ketoglutarate is the amino group acceptor. All aminotransferases have pyridoxal phosphate (PLP) as cofactor. Although the reaction is shown here in the direction of transfer of the amino group to a-ketoglutarate, it is readily reversible. 

The amino acid and nucleotide biosynthetic pathways make repeated use of the biological cofactors pyridoxal phosphate, tetrahydrofolate, and A-adenosylmethionine. Pyridoxal phosphate is required for transamination reactions involving glutamate and for other amino acid transformations. One-carbon transfers require S-adenosyhnethionine and tetrahydrofolate. Glutamine amidotransferases catalyze reactions that incorporate nitrogen derived from glutamine. 

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