Amino acids metabolic pathway

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. 

C. Leucine but none of the other amino acids listed is a branched-chain amino acid. The muscle has a very active branched-chain amino acid metabolic pathway and uses that pathway to provide energy for its own use. The products of leucine metabolism are acetyl-CoA and acetoacetate, which are used in the tricarboxylic acid cycle. Acetoacetate is activated by succinyl-CoA and cleaved to two molecules of acetyl-CoA in the P-ketothiolase reaction. The other branched-chain amino acids, valine, and isoleucine, yield succinyl-CoA and acetyl-CoA as products of their catabolism. 

The physiological relevance together with chnical importance of transamination and deamination is wide-ranging. As an aid to understanding the somewhat complex nature of amino acid metabolism, it can be considered (or imagined) as a metabolic box (represented in Figure 8.13). Some pathways feed oxoacids into the box whereas others remove oxoacids and the ammonia that is released is removed to form urea. The box illustrates the role of transdeamination as central to a considerable amount of the overall metabolism in the liver cell (i.e. protein, carbohydrate and fat metabohsm, see below). 

At this point, the pathways for branched-chain amino acid metabolism diverge. 

Amino Acid Biosynthesis - Pathways, Regulation and Metabolic Engineering... 

T Given that many amino acids are either neurotransmitters or precursors or antagonists of neutrotransmitters, genetic defects of amino acid metabolism can cause defective neural development and mental retardation. In most such diseases specific intermediates accumulate. For example, a genetic defect in phenylalanine hydroxylase, the first enzyme in the catabolic pathway for phenylalanine (Fig. 18-23), is responsible for the disease phenylketonuria (PKU), the most common cause of elevated levels of phenylalanine (hyperphenylalaninemia). 

D-Amino acid oxidase D-Amino acids (see p. 5) are found in plants and in the cell walls of microorganisms, but are not used in the synthesis of mammalian proteins. D-Amino acids are, hew ever, present in the diet, and are efficiently metabolized by 1he liver. D-Amino acid oxidase is an FAD-dependent enzyme that catalyzes the oxidative deamination of these amino acid isomers. The resulting a-ketoacids can enter the general pathways of amino acid metabolism, and be reaminated to L-isomers, or cafe balized for energy. 

Amino acid metabolism shown as a part of the central pathways of energy metabolism. 

Inspection of the amino acid biosynthetic pathways shows that all amino acids arise from a few intermediates in the central metabolic pathways (see fig. 21.1). Amino acids de-rived from a common intermediate are said to be in the same family. For example, the serine family of amino acids, which includes serine, glycine, and cysteine, all arise from glycerate-3-phosphate (see fig. 21.1). The carbon flow from the central metabolic pathways to amino acids is a regulated... 

A mino acid metabolism in vertebrates contrasts sharply with amino acid metabolism in plants and microorganisms. Most striking is the fact that plants and microorganisms can synthesize all 20 amino acids required for protein synthesis whereas vertebrates can only synthesize about half this number. This inability leads to complex nutritional needs for vertebrates. We discuss these needs in light of the pathways for biosynthesis that still exist. 

FIGURE 7 Top-scored metabolite-centric network generated by Ingenuity Pathway Analysis (IPA) describing amino acid metabolism, molecular transport, and small-molecule biochemistry. Microarray results were overlaid in the network highlighting associations between metabolites and transcripts in different canonical pathways (CP). Underlined molecules were downregulated not underlined molecules were upregulated Alp, p70 S6k, and AMPK (marked with an asterisk) were not altered. Reproduced from Ref. (20). 

Mehler AH (1982), Amino acid metabolism I General Pathways, In Devlin TM (Ed.), Textbook of Biochemistry with Clinical Correlations, 2nd Ed. Wiley, New York, pp. 437-452. 

Folic acid participates in the activation of single carbons and in the oxidation and reduction of single carbons. Folate-dependent single-carbon reactions are important in amino acid metabolism and in biosynthetic pathways leading to DNA, RNA, membrane lipids, and neurotransmitters. 

In the preceding sections, attention was focused on amino acid metabolism in the intact animal. We now examine the metabolic pathways of individual amino acids, which take place in the cells of various human tissues. The first reaction in the metabolic pathways of many amino acids is the loss of nitrogen through transamination or deamination. Conversely, the biosynthesis of many non-essential amino acids involves the addition of nitrogen to amino acid precursors amination and transamination. Decarboxylation, or loss of C02, is another reaction shared by many amino acids. 

Figure 20.20 Pathways of branched-chain amino acid metabolism. A, B, C, D, E, and F indicate defects in valinemia, maple syrup urine disease, isovaleric acidemia, /3-hydroxyisovaleric aciduria, a-methyl-j3-hydroxybutyric aciduria, and methylmalonic aciduria, respectively.

Wittmann C, Becker J (2007) The L-lysine story from metabolic pathways to industrial production. In Wendisch VF (ed) Amino acid biosynthesis - pathways, regulation and metabolic engineering. Springer, Berlin... 

Primary carnitine deficiency is caused by a deficiency in the plasma-membrane carnitine transporter. Intracellular carnitine deficiency impairs the entry of long-chain fatty acids into the mitochondrial matrix. Consequently, long-chain fatty acids are not available for p oxidation and energy production, and the production of ketone bodies (which are used by the brain) is also impaired. Regulation of intramitochondrial free CoA is also affected, with accumulation of acyl-CoA esters in the mitochondria. This in turn affects the pathways of intermediary metabolism that require CoA, for example the TCA cycle, pyruvate oxidation, amino acid metabolism, and mitochondrial and peroxisomal -oxidation. Cardiac muscle is affected by progressive cardiomyopathy (the most common form of presentation), the CNS is affected by encephalopathy caused by hypoketotic hypoglycaemia, and skeletal muscle is affected by myopathy. 

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