Alanine transamination

Alanine. Transamination of pyruvate forms alanine (Figure 28-3). 

Alanine. Transamination of alanine forms pyruvate. Perhaps for the reason advanced under glutamate and aspartate catabolism, there is no known metabolic defect of alanine catabolism. Cysteine. Cystine is first reduced to cysteine by cystine reductase (Figure 30-7). Two different pathways then convert cysteine to pyruvate (Figure 30-8). 

For example, coupling alanine transamination (via ALT) with GLDH is shown in Figure 6.6b. A similar scheme can be drawn using, for example, aspartate transaminase in place of alanine transaminase. 

The rate of alanine transamination to pyruvic acid was studied under singleturnover conditions and an 18-fold increase in rate was observed in the pres-... 

L Glutamic acid is not an essential ammo acid It need not be present m the diet because animals can biosynthesize it from sources of a ketoglutaric acid It is however a key intermediate m the biosynthesis of other ammo acids by a process known as transamination L Alanine for example is formed from pyruvic acid by transamination from L glutamic acid... 

Pyridoxamine phosphate serves as a coenzyme of transaminases, e.g., lysyl oxidase (collagen biosynthesis), serine hydroxymethyl transferase (Cl-metabolism), S-aminolevulinate synthase (porphyrin biosynthesis), glycogen phosphoiylase (mobilization of glycogen), aspartate aminotransferase (transamination), alanine aminotransferase (transamination), kynureninase (biosynthesis of niacin), glutamate decarboxylase (biosynthesis of GABA), tyrosine decarboxylase (biosynthesis of tyramine), serine dehydratase ((3-elimination), cystathionine 3-synthase (metabolism of methionine), and cystathionine y-lyase (y-elimination). 

Figure 7-4. Ping-pong mechanism for transamination. E—CHO and E—CHjNHj represent the enzyme-pyridoxal phosphate and enzyme-pyridoxamine complexes, respectively. (Ala, alanine Pyr, pyruvate KG, a-ketoglutarate Glu, glutamate).

Figure 28-3. Formation of alanine by transamination of pyruvate. The amino donor may be glutamate or aspartate. The other product thus is a-ketoglutarate or oxaloacetate.

Unlike the end products of purine catabolism, those of pyrimidine catabolism are highly water-soluble COj, NH3, P-alanine, and P-aminoisobutyrate (Figure 34-9). Excretion of P-aminoisobutyrate increases in leukemia and severe x-ray radiation exposure due to increased destruction of DNA. However, many persons of Chinese or Japanese ancestry routinely excrete P-aminoisobutyrate. Humans probably transaminate P-aminoisobutyrate to methylmalonate semialdehyde, which then forms succinyl-CoA (Figure 19-2). 

Gluconeogenesis in the liver can be fueled by molecules other than pyruvate or lactate. Alanine, a product of protein degradation, yields pyruvate by simple transamination, and this pyruvate can be converted... 

The alanine cycle accomplishes the same thing as the Cori cycle, except with an add-on feature (Fig. 17-11). Under conditions under which muscle is degrading protein (fasting, starvation, exhaustion), muscle must get rid of excess carbon waste (lactate and pyruvate) but also nitrogen waste from the metabolism of amino acids. Muscle (and other tissues) removes amino groups from amino acids by transamination with a 2-keto acid such as pyruvate (oxaloacetate is the other common 2-keto acid). 

The result is that the amino groups can be dumped out as alanine (the transamination product of pyruvate). In the liver and kidney, alanine is transaminated to yield pyruvate and glutamate. As in the Cord cycle, the pyruvate is converted to glucose by the liver and is shipped out. The glutamate is fed into the urea cycle-nitrogen disposal system to get rid of the excess nitrogen. 

Back in 1937, Braunstein and Kritzman and, independently, Herbst, had proposed transamination might proceed via a Schiff s base formation. The essential lability of the H atom on the a-C atom was shown with deuterium labelling (1942). a-2H alanine released 2H into the medium during transamination. The label did not appear in glutamate, the end-product. 

Glycogenolysis and glycogen synthesis P-oxidation of fatty acids transamination and deamination of amino acids Cori cycle and glucose-alanine cycle, which recycles substrates between muscle and liver. 

Muscle protein catabolism generates amino acids some of which may be oxidized within the muscle. Alanine released from muscle protein or which has been synthesized from pyruvate via transamination, passes into the blood stream and is delivered to the liver. Transamination in the liver converts alanine back into pyruvate which is in turn used to synthesise glucose the glucose is exported to tissues via the blood. This is the glucose-alanine cycle (Figure 7.11). In effect, muscle protein is sacrificed in order to maintain blood adequate glucose concentrations to sustain metabolism of red cells and the central nervous system. 

Transamination of alanine yields pyruvate catalysed by alanine transaminase (ALT) whilst aspartate produces oxaloacetate catalysed by aspartate transaminase (AST). All transaminase enzymes operate close to a true equilibrium (K eq 1, see Chapter 2) and... 

The intervention of a metal ion in the stoichiometry of a reaction has been illustrated several times previously. Reaction is forced to completion in ester hydrolysis since the carboxylate grouping forms a more stable complex than the ester moiety does. A similar driving force underlies the formation of macrocycles and the completion of transamination by formation of the metal-Schiff base complex. The latter is particularly relevant in dilute solution and at low pH. For example, the extent of aldimine formation between pyridoxal and alanine is undetectable at the physiological pH but occurs to the extent of = 10% in the presence of zinc... 

After formation of the aldimine, numerous factors in the enzyme facilitate deprotonation of the a-carbon (Fig. 3, Step II). The lysine liberated by transimi-nation is utilized as a general base and is properly oriented for effective deprotonation [11]. Furthermore, the inductive effects of the ring system are tuned to increase the stabilization of the quinoid intermediate. For example, the aspartate group that interacts with the pyridyl nitrogen of the co enzyme promotes proto-nation to allow the ring to act as a more effective electron sink. In contrast, in alanine racemase, a less basic arginine residue in place of the aspartic acid is believed to favor racemization over transamination [12]. 

Table 2. Observed rate constants for the transamination of pyruvate to alanine mediated by various pyridoxal derivatives...

The ability of peptides CBPOl-GBP 18 to modulate pyridoxamine-mediated transamination was determined by the conversion of pyruvic acid to alanine in both the absence and presence of copper(II) ion, which would be coordinated by the transamination intermediates [32]. In the absence of copper(II) ion,peptide CBP13 showed up to a 5.6-fold increase in alanine production relative to a pyridoxamine model compound and peptide CBP14 produced alanine with a 27% ee of the 1-enantiomer. In the presence of copper(II) ion, peptide CBP13 again showed the greatest increase in product production, with a 31.7-fold increase in alanine production relative to the pyridoxamine model compound. Peptide CBPIO showed optical induction for D-alanine with a 37% ee. 

Figure 8.11 Five near-equilibrium reactions involved in transamination of five different amino adds. Three enzymes are involved in these reactions (1) alanine aminotransferase (2) aspartate aminotransferase (3) branched-chain amino acid aminotransferase, i.e. one enzyme catalyses the three reactions. (The branched-chain amino acids are essential.)...

Figure 8.25 Excess ammonia in the muscle is used to form alanine. Ammonia is released from several reactions and is incorporated into alanine via glutamate dehydrogenase and transamination. OG - oxoglutarate. Alanine is released into the blood from volece it is removed by the liver.

Figure 8.29 The initial reactions of glutamine metabolism in kidney, intestine and cells of the immune system. The initial reaction in all these tissues is the same, glutamine conversion to glutamate catalysed by glutaminase the next reactions are different depending on the function of the tissue or organ. In the kidney, glutamate dehydrogenase produces ammonia to buffer protons. In the intestine, the transamination produces alanine for release and then uptake and formation of glucose in the liver. In the immune cells, transamination produces aspartate which is essential for synthesis of pyrimidine nucleotides required for DNA synthesis otherwise it is released into the blood to be removed by the enterocytes in the small intestine or by cells in the liver.

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