Alanine catabolism

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). 

Figure 2.3(D). Uricogenesis during alanine catabolism and gluconeogenesis in avian liver. Some abbreviations are as in figure 2.3(C). 1 C refers to one-carbon units MDH, malate dehydrogenase XDH, xanthine dehydrogenase PRPP, phosphoribosylpyrophosphate IMP, inosoine monophosphate ino, inosine hyp, hypoxanthine xan, xanthine.

In helminths alanine is an end-product of anaerobic glycolysis and may be formed from glutamine during aerobic metabolism (28). Alanine catabolism has also been demonstrated. In addition to COj, products such as lactate, acetate and ethanol are formed indicating only partial oxidation and a relatively low energy efficiency (28). 

Serine, like alanine, is converted into pyruvate by a PLP-dependent pathway, but the two reaction sequences are not the same. Whereas alanine catabolism involves a PLP-dependent transamination, serine catabolism involves a PLP-dependent dehydration to form an intermediate enamine that is then hydrolyzed. 

Figure 30-2. Catabolism of i-as-paragine (top) and of i-glutamine (bottom) to amphibolic intermediates. (PYR, pyruvate ALA, i-alanine.) In this and subsequent figures, color highlights portions of the molecules undergoing chemical change.

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). 

Since the end products of pyrimidine catabolism are highly water-soluble, pyrimidine overproduction results in few clinical signs or symptoms. In hypemricemia associated with severe overproduction of PRPP, there is overproduction of pyrimidine nucleotides and increased excretion of p-alanine. Since A, A -methyl-ene-tetrahydrofolate is required for thymidylate synthesis, disorders of folate and vitamin Bjj metabofism result in deficiencies of TMP. 

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. 

Dihydropyrimidine dehydrogenase is the first and the rate-limiting enzyme in the three-step metabolic pathway involved in the degradation of the pyrimidine bases uracil and thymine. In addition, this catabolic pathway is the only route for the synthesis of p-alanine in mammals. 

A major aim of amino acid catabolism is removal of the a-NH2 group, which results in the formation of ammonia which is then converted to urea. The removal of the a-NH2 group for most amino acids results in the formation of a carbon-compound, which is usually an oxoacid (e.g. the oxoacid for alanine is pyruvate). 

Most of the amino acids are consumed by insect cells, with the exception of alanine which is produced however, it has been reported that alanine overflow metabolism is energetically wasteful as it is with mammalian cells [63]. The alanine production by insect cells has been interpreted as a strategy to avoid the accumulation of toxic ammonia produced from amino acid catabolism [64]. 

The oxidation of pyruvate is an important catabolic process, but pyruvate has anabolic fates as well. It can, for example, provide the carbon skeleton for the synthesis of the amino acid alanine. We return to these anabolic reactions of pyruvate in later chapters. 

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... 

Phenylalanine and tyrosine Hydroxylation of phenylalanine leads to the formation of tyrosine (Figure 20.7). This reaction, catalyzed by phenylalanine hydroxylase, is the first reaction in the catabolism of phenylalanine. Thus, the metabolism of phenyl alanine and tyrosine merge, leading ultimately to the formation of fumarate and acetoacetate. Phenylalanine and tyrosine are, therefore, both glucogenic and ketogenic. 

Returning to the major tryptophan catabolic pathway, marked by green arrows in Fig. 25-11, formate is removed hydrolytically (step c) from the product of tryptophan dioxygenase action to form kynurenine, a compound that is acted upon by a number of enzymes. Kynureninase (Eq. 14-35) cleaves the compound to anthranilate and alanine (step d), while transamination leads to the cyclic kynurenic acid (step e). Hie latter is dehydroxylated in an unusual reaction to quinaldic acid, a prominent urinary excretion product. 

Enzymes present in mammalian liver are capable of the catabolism of both uracil and thymine. The first reduces uracil and thymine to the corresponding 5,6-dihydro derivatives. This hepatic enzyme uses NADPH as the reductant, whereas a similar bacterial enzyme is specific for NADH. Similar enzymes are apparently present in yeast and plants. Hydropyrimidine hydrase then opens the reduced pyrimidine ring, and finally the carbamoyl group is hydrolyzed off from the product to yield /3-alanine or /3-aminoisobutyric acid, respectively, from uracil and thymine (see fig. 23.23). 

In contrast to the catabolic nature of /7-alanine and /7-aminobutyric acid biosynthesis, the generation of higher /7-amino acids usually starts from the corresponding a-amino acid. The shift of the amino group is catalyzed by different types of aminomutase. 

Some catabolic reactions of amino acid carbon chains are easy transformations to and from TCA cycle intermediates—for example, the transamination of alanine to pyruvate. Reactions involving 1-carbon units, branched-chain, and aromatic amino acids are more complicated. This chapter starts with 1-carbon metabolism and then considers the catabolic and biosynthetic reactions of a few of the longer side chains. Amino acid metabolic pathways can present a bewildering amount of material to memorize. Perhaps fortunately, most of the more complicated pathways lie beyond the scope of an introductory course or a review such as this. Instead of a detailed listing of pathways, this chapter concentrates on general principles of amino acid metabolism, especially those that occur in more than one pathway. 

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