Threonine transamination

Removal of a-amino nitrogen by transamination (see Figure 28-3) is the first catabolic reaction of amino acids except in the case of proline, hydroxyproline, threonine, and lysine. The residual hydrocarbon skeleton is then degraded to amphibolic intermediates as outhned in Figure 30-1. 

The wild type ilvA gene was modified to target the protein to the plastid and expressed in A. thaliana. Transgenic plants showed a 20-fold increase in levels of 2-ketobutyrate as well as a large increase in 2-aminobutyrate, the transaminated product of 2-ketobutyrate [27, 41]. The levels of threonine remained stable whereas isoleucine concentration increased. Constitutive expression of the ilvA protein along with bktB, phaA, and phaC proteins in the plastids of A. thaliana led to the synthesis of poly(3HB-co-3HV) in the range of 0.2 - 0.8 % dry weight, with a HV level between 4-17 mol % [27,41]. Co-expression of the iso-... 

The carbon skeletons of six amino acids are converted in whole or in part to pyruvate. The pyruvate can then be converted to either acetyl-CoA (a ketone body precursor) or oxaloacetate (a precursor for gluconeogenesis). Thus amino acids catabolized to pyruvate are both ke-togenic and glucogenic. The six are alanine, tryptophan, cysteine, serine, glycine, and threonine (Fig. 18-19). Alanine yields pyruvate directly on transamination with... 

C Amino acid s Asn is hydrolyzed in one step to aspaartate, which in turn is transaminated in one step to oxalacetate. Threonine feeds into the TCA cycle through succinyl-CoA instead of oxalacetate. Thr is first deaminated via a dehydratase as seen earlier, then decarboxylated by Pyruvate DH Complex to give propionyl-CoA, which is then transformed via a series of steps to give succinyl-CoA. 

All of the amino acids except lysine, threonine, proline, and hydroxyproline participate in transamination reactions. Transaminases exist for histidine, serine, phenylalanine, and methionine, but the major pathways of their metabolism do not involve transamination. Transamination of an amino group not at the a-position can also occur. Thus, transfer of 3-amino group of ornithine to a-ketoglutarate converts ornithine to glutamate-y-semialdehyde. 

The pyridoxal biosynthetic pathway is outlined in Fig. 37. Oxidation of 196 followed by transamination gives 4-hydroxy-L-threonine-4-phosphate 199 [171]. Condensation with l-deoxy-o-xylulose (see also ubiquinone and thiamin sections) and a final oxidation gives the cofactor [172-175]. 

Because transamination reactions are reversible, it is theoretically possible for all amino acids to be synthesized by transamination. However, experimental evidence indicates that there is no net synthesis of an amino acid if its a-keto acid precursor is not independently synthesized by the organism. For example, alanine, aspartate, and glutamate are nonessential for animals because their a-keto acid precursors (i.e., pyruvate, oxaloacetate, and a-ketoglutarate) are readily available metabolic intermediates. Because the reaction pathways for synthesizing molecules such as phenylpyruvate, a-keto-/Thydroxybutyrate, and imidazolepyruvate do not occur in animal cells, phenylalanine, threonine, and histidine must be provided in the diet. (Reaction pathways that synthesize amino acids from metabolic intermediates, not only by transamination, are referred to as de novo pathways.)... 

The syntheses of valine, leucine, and isoleucine from pyruvate are illustrated in Figure 14.9. Valine and isoleucine are synthesized in parallel pathways with the same four enzymes. Valine synthesis begins with the condensation of pyruvate with hydroxyethyl-TPP (a decarboxylation product of a pyruvate-thiamine pyrophosphate intermediate) catalyzed by acetohydroxy acid synthase. The a-acetolactate product is then reduced to form a,/3-dihydroxyisovalerate followed by a dehydration to a-ketoisovalerate. Valine is produced in a subsequent transamination reaction. (a-Ketoisovalerate is also a precursor of leucine.) Isoleucine synthesis also involves hydroxyethyl-TPP, which condenses with a-ketobutyrate to form a-aceto-a-hydroxybutyrate. (a-Ketobutyrate is derived from L-threonine in a deamination reaction catalyzed by threonine deaminase.) a,/3-Dihydroxy-/3-methylvalerate, the reduced product of a-aceto-a-hydroxybutyrate, subsequently loses an HzO molecule, thus forming a-keto-/kmethylvalerate. Isoleucine is then produced during a transamination reaction. In the first step of leucine biosynthesis from a-ketoisovalerate, acetyl-CoA donates a two-carbon unit. Leucine is formed after isomerization, reduction, and transamination. 

Serine and threonine dehydrases. Serine and threonine are not substrates in transamination reactions. Their amino groups are removed by the pyridoxal phosphate-requiring hepatic enzymes serine dehydratase and threonine dehydratase. The carbon skeleton products of these reactions are pyruvate and a-keto-butyrate, respectively. 

All amino acids except lysine and threonine can reversibly transaminate. All amino acids except lysine and leucine are at least partially glucogenic (i.e., provide the carbon atoms for the formation of glucose). 

Aspartate is involved in the control point of pyrimidine biosynthesis (Reaction 1 below), in transamination reactions (Reaction 2 below), interconversions with asparagine (reactions 3 and 4), in the metabolic pathway leading to AMP (reaction 5 below), in the urea cycle (reactions 2 and 8 below), IMP de novo biosynthesis, and is a precursor to homoserine, threonine, isoleucine, and methionine (reaction 7 below). It is also involved in the malate aspartate shuttle. 

Valine, leucine, and isoleucine - The synthetic pathway from threonine and pyruvate to valine, leucine and isoleucine is outlined in Figure 21.26. The last four reactions in the biosynthesis of valine and isoleucine are catalyzed by the same four enzymes. Threonine dehydratase, which catalyzes the first step in conversion of threonine to isoleucine, is inhibited by isoleucine. Leucine, isoleucine, and valine are all catabolized via transamination followed by oxidative decarboxylation of the respective keto-acids (see here) and oxidation. The oxidation is similar to fatty acid oxidation, except for a debranching reaction for each intermediate. 

While the 2-oxobutyrate needed for isoleucine formation is shown as originating from threonine in Eig. 24-17, bacteria can often make it in other ways, e.g., from glutamate via p-methylaspartate (Eig. 24-8) and transamination to the corresponding 2-oxoacid. It can also be made from pyruvate by chain elongation using acetyl-CoA (Eig. 17-18) citramalate and mesa-conate (Eig. 24-8) are intermediates. This latter pathway is used by some methanogens as are other alternative routes. The first step unique to the biosynthetic pathway to leucine is the reaction of the... 

All amino acids except lysine and threonine undergo transamination reactions. The enzymes catalyzing these reactions are known as transaminases or aminotransferases. For most of these reactions, a-ketoglutarate and glutamate serve as one of the a-keto acid-amino acid pairs. Pyridoxal phosphate is the cofactor, and the mechanism of the reaction is indicated in Figure 38.4. 

In 1966 Dunathan (18) proposed that, in PLP-mediated reactions, the bond to be broken in the substrate-cofactor compound should be perpendicular to the plane of the extended conjugated system so that there would be maximum a-n overlap between the breaking bond and the ring-imine n system. Thus 3a, 3b, and 3c represent the conformations of the imine 3 best suited to achieve transamination reactions, decarboxylation reactions, and retroaldol reactions, respectively. The enzyme will be responsible for the orientation of the amino acid-PLP complex and thus dictate the nature of the resultant reaction. An example of an enzyme catalyzing two distinct reactions was found for serine hydroxymethyltransferase (EC 2.1.2.1), which normally catalyzes the retroaldol process outlined in 3c when L-serine or L-threonine are substrates. When D-alanine was used as substrate, however, a slow transamination was observed (19). Comparison of the conformations of the amino acid-PLP complexes, 3c and 17, respectively, for the retroaldol and transamination reactions shows that both the proton removed from the... 

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