Glutamate transamination reactions

Most amino acids lose their nitrogen atom by a transamination reaction in which the -NH2 group of the amino acid changes places with the keto group of ct-ketoglutarate. The products are a new a-keto acid plus glutamate. The overall process occurs in two parts, is catalyzed by aminotransferase enzymes, and involves participation of the coenzyme pyridoxal phosphate (PLP), a derivative of pyridoxine (vitamin UJ. Different aminotransferases differ in their specificity for amino acids, but the mechanism remains the same. 

Write all the steps in the transamination reaction of PMP with a-ketoglutarate plus a lysine residue in the enzyme to give the PLP-enzyme inline plus glutamate. 

This shows that glutamate is the ammonia donor. Glutamate itself may be formed from other amino acids by transamination reactions, thus allowing... 

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 ... 

Figure 8.10 A summaiy of the processes involved in transdeamination. (1) transamination (2) glutamate dehydrogenase. The glutamate dehydrogenase reaction results in ammonia production. The oxoacids are further metabolised to CO , glucose or fat.

The fumarate produced in step [4] is converted via malate to oxaloacetate [6, 7], from which aspartate is formed again by transamination [9]. The glutamate required for reaction [9] is derived from the glutamate dehydrogenase reaction [8], which fixes the second NH4 " in an organic bond. Reactions [6] and [7] also occur in the tricarboxylic acid cycle. However, in urea formation they take place in the cytoplasm, where the appropriate isoenzymes are available. 

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. 

In the transamination reaction, in the presence of transaminase enzymes, (S)-glutamic acid reacts with the a-keto acid analog of the desired a-amino acid to give the desired (S)-amino acid and the keto analog of glutamic acid. 

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. 

Alanine, aspartate, and glutamate are synthesized by transfer of an amino group to the a-keto acids pyruvate, oxaloacetate, and a-keto-glutarate, respectively. These transamination reactions (Figure 20.12, and see p. 248) are the most direct of the biosynthetic pathways. Glutamate is unusual in that it can also be synthesized by the reverse of oxidative deamination, catalyzed by glutamate dehydrogenase (see p. 249). 

The phosphate ester of the aldehyde form of vitamin B6, pyridoxal phosphate (pyridoxal-P or PLP), is required by many enzymes catalyzing reactions of amino acids and amines. The reactions are numerous, and pyridoxal phosphate is surely one of nature s most versatile catalysts. The story begins with biochemical transamination, a process of central importance in nitrogen metabolism. In 1937, Alexander Braunstein and Maria Kritzmann, in Moscow, described the transamination reaction by which amino groups can be transferred from one carbon skeleton to another.139 140 For example, the amino group of glutamate can be transferred to the carbon skeleton of oxaloacetate to form aspartate and 2-oxoglutarate (Eq. 14-24). 

This transamination reaction is a widespread process of importance in many aspects of the nitrogen metabolism of organisms. A large series of transaminases (aminotransferases), for which glutamate is most often one of the reactants, have been shown to catalyze the reactions of other oxoacids and amino acids.141-143... 

Acetamidodeoxyhexoses. A further modification of the 4-keto-inter-mediate has been independently shown by Ashwell and by Strominger and associates (Table I, References 20, 21, 22, 23). Transamination reactions with L-glutamate as the amino donor and pyridoxal phosphate as coenzyme led to formation of 3-amino 3,6-dideoxy- and 4-amino 4,6-dideoxyhexoses, respectively. Acetylation with acetyl coenzyme A yields the naturally-occurring N-acetyl amino sugar derivatives. 

At pH 7.5 less than 1% of the compound exists in the open-chain a-keto-acid form while at pH 9 approximately 3% is in a form that reacts as a typical a-keto acid. Glutamine transaminase also catalyzes the transamination of glutamic acid y-A -methylamide the expected transamination product, a-keto-A-methylglutaramic acid has not yet been isolated from a transamination reaction mixture. However, this compound was... 

The glucose-alanine cycle. Active muscle functions anaerobically and synthesizes alanine by a transamination reaction between glutamate and pyruvate, The alanine is transported to the liver, where the... 

The other part of the urea cycle that has occurred is the conversion of the carbons of aspartate to fumarate. The fumarate is recycled back to oxaloacetate through TCA cycle reactions in the mitochondrion. Transamination with glutamate regenerates aspartate. The glutamate comes from the glutamate dehydrogenase reaction. 

Glutamate provides the amino group for the synthesis of many other amino acids through transamination reactions in all cells. These amino acids are then used for protein synthesis and other aspects of nitrogen metabolism. The majority of animals are dependent on plant or animal proteins for fixed nitrogen, for their nitrogen metabolism. 

---