Alanine and the Branched-Chain Amino Acids

Ammonium Ions 1391 E. Alanine and the Branched-Chain Amino Acids... 

In the branched-chain amino acids (Val, Leu, He) and also tyrosine and ornithine, degradation starts with a transamination. For alanine and aspartate, this is actually the only degradation step. The mechanism of transamination is discussed in detail on p. 178. 

The skeletal muscle is the most important site for degradation of the branched-chain amino acids (Val, Leu, lie see p. 414), but other amino acids are also broken down in the muscles. Alanine and glutamine are resynthesized from the components and released into the blood. They transport the nitrogen that arises during amino acid breakdown to the liver (alanine cycle see above) and to the kidneys (see p. 328). 

Leloir s discovery of UDP-glucose at about the same time provided the answer. Persons with McArdle syndrome are greatly benefit-ted by a high-protein diet, presumably because amino acids such as alanine and glutamine are converted efficiently to glucose and because branched-chain amino acids may serve as a direct source of muscle energy.c,d... 

As indicated in Fig. 24-17, pyruvate is the starting material for the formation of both l- and D-alanine and also the branched chain amino acids valine, leucine, and isoleucine.339,340 The chemistry of the reactions has been discussed in the sections indicated in the figure. The first step is catalyzed by the thiamin diphosphate-dependent acetohydroxyacid synthase (acetolactate synthase), which joins two molecules of pyruvate or one of pyruvate and one of 2-oxobutyrate (Fig. 24-17 Fig. 14-3).340a b In E. coli there are two isoenzymes encoded by genes ilv B and ilv HI. Both are regulated by feedback inhibition by valine, probably... 

Reviews by Ruderman (19) and Adibi (20,21) indicate that the branched-chain amino acids, particularly leucine, have an important role along with alanine in gluconeogenesis. Leucine and the other two branched-chain amino acids are catabolized in skeletal muscle. The nitrogen that is removed from the branched-chain amino acids in skeletal muscle is combined with pyruvate and returned to the liver as alanine. In the liver the nitrogen is removed for urea production and the carbon chain is utilized as substrate for synthesis of glucose. Adibi et al. (22) reported that during the catabolic conditions of starvation, oxidation of leucine and fatty acids increases in skeletal muscles. While glucose oxidation is reduced, the capacity for oxidation of the fatty acid palmltate more than doubled, and leucine oxidation increased by a factor of six. 

The effects of exercise on branched-chain amino acids may be unique. The branched-chain amino acids are essential in the diet and are uniquely catabolized in skeletal muscles. These amino acids may provide an energy source for muscles or may serve an intermediate role in maintaining blood glucose through production of alanine via transamination with pyruvate in muscles (19). 

The glucose-alanine cycle between the liver and the musculature is particularly significant. In muscle tissue, ammonia is generated during the degradation of amino acids (particularly the branched-chain amino acids). The transfer of ammonia to pyruvate yields alanine, which is then transported through the bloodstream to... 

Net breakdown of muscle can occur with either exercise or prolonged fasting. The mechanisms that control the breakdown of the various types of protein found in muscle are not well understood. It has, however, been established that while the branched-chain amino acids (BCAAs) released tend to be oxidized for energy in the muscle cell, other released amino acids enter the bloodstream for catabolism, and perhaps gluconeogenesis, in the liver Examination of the amino acids released from skeletal muscle reveals an apparent anomaly alanine accounts for or ly about 6% of the amino acids of muscle, but for about 35% of the amino acids released from muscle during exerdse. 

The branched-chain amino acids are oxidized by muscle to produce energy. Some of the carbons are converted to glutamine and alanine. 

The liver uses alanine, along with serine, to manufacture glucose. Phenylalanine, glycine and proline levels are not affected to any greater extent than that seen in other tissues. The concentrations of the branched chain amino acids isoleucine and valine in blood remain unchanged. 

The branched-chain amino acids, or BCAA (valine, isoleucine, and leucine) are oxidized principally in skeletal muscle and other tissues and not in the liver. In skeletal muscle, the carbon skeletons and some of the nitrogen are converted to glutamine, which is released into the blood. The remainder of the nitrogen is incorporated into alanine, which is taken up by the liver and convened to urea and glucose. 

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