Pyruvate transamination

Muscle activity involves processes such as aerobic and anaerobic glycolysis and is therefore accompanied by an increased pyruvate production. Consequently, the pyruvate transamination product alanine will be increased after exercise. Heavy exercise may be associated with an increased need of creatine biosynthesis from arginine. Ornithine is a by-product of this pathway and may be increased under these conditions. 

The most common acceptors of amino groups in transamination reactions are a-ketoglutarate, oxaloacetate, and pyruvate. Transamination reactions are readily reversible. Some amino acids, such as lysine, do not transaminate in the manner indicated in Equation (20.7). 

The biosynthesis of lysine in higher plants involves the formation of a, e-diaminopimelate from aspartate and pyruvate. Transamination of this intermediate to the diketo compound and reduction of one carboxyl group to an aldehyde function may produce a compound capable of cyclization via aldol condensation, i.e., the C4 -I- C3 pathway. ... 

Imidazolone propionate hydrolase catalyzes the enzymatic cleavage of the imidazole ring to yield formi-minoglutamate. The rat liver enzyme has been partially purified. In addition to the enzymic conversion, two nonenzymic spontaneous reactions yield N-formyl-isoglutamine and 4-oxoglutamic acid. In addition to the oxidative pathways for histidine, there exist three other pathways for its use protein synthesis, decarboxylation to yield histamine (see Inflammation), and transaminase. The activity of histidine pyruvic transamination in rat liver is three times that of histidase. The product of the transaminase reaction is imidazole pyruvic acid, which in turn is converted to imidazole acetic acid. 

It has long been thought from our knowledge of these two systems that one of the members of the pair of substrates for a transaminase must be a dicarboxylic add. Since then, leucine-pyruvate, phenylalanine-pyruvate and ornithine-pyruvate transaminations have been demonstrated. However it is not possible to exclude the presence of a trace of glutamate, thus ... 

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... 

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... 

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).

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

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.

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). 

Transamination is the most common initial reaction of amino acid catabohsm. Subsequent reactions remove any additional nitrogen and restmcmre the hydrocarbon skeleton for conversion to oxaloacetate, a-ketoglutarate, pyruvate, and acetyl-CoA. 

These points have important functional implications. While neuronal glutamate may come from glucose via pyruvate, the Krebs cycle and transamination of alpha-oxoglutamate, it seems likely that most of the transmitter originates from the deamination of glutamine. After release, the high-affinity uptake sites (transporters)... 

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. 

It was then possible to confirm the existence of two transaminating systems, the original one utilizing pyruvate as amino acceptor, and a second which used oxaloacetate. Both enzymes were purified and found to be very specific for their substrates. The reactions catalyzed were freely reversible. 

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 same group have used the enzyme combination employed in the aspartate deracemization cited above to deracemize 2-naphthylalanine, hut have made use of an interesting innovation introduced by Helaine et al to pull over the poised equilibrium of the transamination reaction. Cysteine sulphinic acid was used as the amino donor in the transamination. The oxoacid product spontaneously decomposes in to pyruvic acid and SO2 (Scheme 3). 

The investigation of the aminotransferase activity of apple ACS carried out by Feng et al reveals that it is able to reductively aminate PLP to PMP by transamination of some L-amino acids to their corresponding a-keto acids. The enzyme has shown substrate specificity with the preference of Ala > Arg > Phe > Asp. The addition of excess pyruvate causes a conversion of the PMP form of the enzyme back to the PLP form. The quite unstable PMP form of ACS can generate apoenzyme, which captures PLP to restore its physiologically active form. 

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