Principles of Amino Acid Metabolism

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. 

Longo N Inherited Disorders of Amino Acid Metabolism and Storage. Harrison s Principles of Internal Medicine. Eugene Braunwald (ed). 15th Edition. New York, NY. The McGraw-Hill Companies, Inc. 2001. Chap 352 2301-2309-... 

Rosenberg, L. E. (1991). Inherited disorders of amino acid metabolism. In "Principles of Internal Medicine" Q. Wilson, E, Braunwald, K. J. Jsselbacher, K. G. Petersdorf, J. B. Martin, A. Fauci, and R. K. Root, eds.), pp. 1868-1875. McGraw-Hill, New York. 

The aims of this contribution are to (i) consider the theoretical principles underlying the use of compound-specific stable isotope analysis in archaeology (ii) consider the practical aspects of undertaking compound-specific stable isotope analyses and (iii) demonstrate the value of linking the structures of amino acids, fatty acids and/or sterols, to their compound-specific stable isotope values to achieve new insights into variations in metabolism and environment in order to enhance archaeological interpretations. 

The various reactions of pyridoxal phosphate in amino acid metabolism shown in Table 9.1 all depend on the same chemical principle - the ability to stabilize amino acid carbanions and to labilize bonds about the a-carbon, by... 

Figure 1 The retrobiosynthetic principle. Labeling patterns of central metabolic intermediates (shown in yellow boxes) are reconstructed from the labeling patterns of sink metabolites, such as protein-derived amino acids, storage metabolites (starch and lipids), cellulose, isoprenoids, or RNA-derived nucleosides. The reconstruction is symbolized by retro arrows following the principles of retrosynthesis in synthetic organic chemistry. The figure is based on known biosynthetic pathways of amino acids, starch, cellulose, nucleosides, and isoprenoids in plants. The profiles of the central metabolites can then be used for predictions of the labeling patterns of secondary metabolites. In comparison with the observed labeling patterns of the target compounds, hypothetical pathways can be falsified on this basis.

This book contains only subject matter covered at MU, and the chapters are authored by the experts who presented the material. Therefore, it is not a comprehensive treatise on IMD but rather a textbook on the most frequently encountered challenges in IMD nutrition. The book contains introductory chapters on nutrition and metabolism principles common to many metabolic disorders and disease-specific chapters on disorders of amino acid, fat, and carbohydrate metabolism. Appendix M contains an overview of nutrition management of IMD including those disorders for which there is not a specific chapter. 

Glycolysis is the major route of carbohydrate metabolism in all cell types and the TCA is a focal point allowing the integration of carbohydrate, amino acid and lipid metabolism. The two pathways are illustrated in Figures 3.9 and 3.14. These two well-known pathways exemplify many of the general principles of metabolic regulation described above. 

The principles of the above reactions form the basis of a series of important metabolic interconversions involving the coenzyme pyridoxal phosphate (structure 2.41). This condenses with amino acids to form a Schiff base (structure 2.42). The pyridine ring in the Schiff base acts as an electron sink which very effectively stabilizes a negative charge. 

Altering the control of metabolic pathways can also be achieved by genetic manipulation. As proteins are generated using the template stored as a fragment of DNA, the structure of the allosteric enzyme may be altered so that there is little or no regulatory control. It is therefore possible to generate mutants that over-produce metabolites, and techniques based on this principle have been most widely exploited in amino-acid and nucleotide production 2 . 

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