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In this chapter, we have seen that the metabolism of amino acids is integrally related to the mainstream of metabolism. The catabolism of amino acids generally begins with the removal of the α-amino group, which is transferred to α-ketoglutarate and oxaloacetate, and ultimately excreted in the form of urea. The resulting carbon skeletons are converted to an intermediate(s) that enter central metabolism at various points. Because carbon skeletons corresponding to the various amino acids can be derived from or feed into the glycolytic pathway, the TCA cycle, fatty acid biosynthesis and gluconeogenesis, amino acid metabolism should not be considered as an isolated pathway. Although amino acids are not stored like glucose (glycogen) or fatty acids (triacylglycerols), they have an important and dynamic role, not only in providing the building blocks for the synthesis and turnover of protein, but also in normal energy metabolism, providing a carbon source for
gluconeogenesis when needed and an energy source of last resort in starvation. In addition, amino acids provide precursors for the biosynthesis of a variety of small signaling molecules, including hormones and neurotransmitters. The severe consequences of abnormal metabolism evident in inherited diseases such as phenylketonuria (PKU) and maple syrup urine disease illustrate the consequences of abnormal amino acid metabolism.
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- Tyrosine is included as a supplement in the diet plan for individuals with phenylketonuria. What is the rationale for this supplement? Compare the therapeutic approaches used for treatment of the various forms of PKU in which phenylalanine hydroxylase is not affected.
- Review the rationale for use of levodopa, catechol-O-methyl transferase inhibitors and monoamine oxidase inhibitors for treatment of Parkinson's disease.
- Review the pathways for biosynthesis of the neurotransmitters: serotonin, melatonin, dopamine and the catecholamines. What enzymes are involved in the inactivation of these compounds?
- Discuss the metabolic fate of lysine in humans.
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| Berry GT, Steiner RD. Long-term Management of Patients with Urea Cycle Disorders. J Pediatr 2001;138(1 Suppl):S56-60.
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Cederbaum S. Phenylketonuria: an update. Curr Opin Pediatr 2002;14:702-706.
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| Ogier de Baulny H, Saudubray JM. Branched-chain organic acidurias. Semin Neonatal 2002;7:65-74.
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| Pitt JJ, Eggington, M. and Kahler, SG. Comprehensive screening of urine samples for inborn errors of metabolism by electrospray tandem mass spectrometry. Clinical Chemistry 2002;48:1970-1980.
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| Saudubray JM, Nassogne MC, de Lonlay P, Touati G. Clinical approach to inherited metabolic disorders in neonates: an overview. Semin Neonatal 2002;7:3-15.
Full article
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| Steiner RD, Cederbaum SD. Laboratory evaluation of urea cycle disorders. J Pediatr 2001;138(Suppl 1):S21-S29.
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| Zytkovicz, TH, Fitzgerald EF, Marsden D, et al. Tandem mass spectrometric analysis for amino acid, organic and fatty acid disorders in newborn dried blood spots. Clin Chem 2001;47:1945-1955.
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| Disorders of amino acid metabolism: www.gpnotebook.co.uk/cache/-1811546080.htm
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| Urea cycle: www.nucdf.org
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| PKU: www.pku-allieddisorders.org; www.pkunews.org
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| MSUD: www.msud-support.org/overv.htm
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| Parkinson's Disease: www.pdf.org; www.parkinsons.org.uk; www.wpda.org
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