Amino Acid Metabolism

This chapter is a revision of the previous edition's chapter by Raymond Y. Wang, William R. Wilcox, and Stephen D. Cederbaum, Chapter 92, Amino Acid Metabolism, pp 2564–2605 © 2013, Elsevier Ltd. (Wang et al., 2013). The inborn errors of amino acid metabolism are a family of genetic conditions in which an enzyme deficiency results in the accumulation of a ninhydrin-positive amino acid or a proximal metabolite. They are conceptually identical to disorders caused by enzyme defects that result in the accumulation of the organic acid intermediates (see Chapter 8 ). The current chapter strives to highlight the clinical, biochemical, molecular, and pathologic features of defects in aromatic amino acid processing and related neurotransmitter metabolism disorders, disorders of glycine metabolism, defects in the processing of sulfur-containing amino acids, disorders of branched-chain amino acid metabolism, proline metabolism, urea cycle disorders, and defects of serine synthesis. As our understanding of the dynamics of amino acid metabolism grows, simplistic notions of metabolic pathways solely as conduits for elimination of excess substrate have been abandoned. We now realize that most, if not all, of these reactions are highly regulated and integrated into the total fabric of metabolic homeostasis in which amino acids play an important role. Nevertheless, such considerations are largely beyond the scope of this concise overview and are covered in more detail in the work by Valle and colleagues, 2014, the standard reference work on these and other inborn errors of metabolism and one that explores the physiologic interactions more fully. Much of the current information on the molecular aspects of these disorders can be accessed through the Online Mendelian Inheritance in Man database (OMIM; http://www.ncbi.nlm.nih.gov/omim ). This chapter strives to highlight the clinical, biochemical, molecular, and pathologic features of these inborn errors of metabolism. Although synthesized to provide a quick reference for a geneticist with an affected individual carrying an established diagnosis of a disorder of amino acid metabolism in practice, physicians may encounter undiagnosed affected individuals with specific symptoms in search of an explanation. The clinical features and diagnostic testing described in the following sections will aid the physician in deciding whether specific diagnostic tests as plasma amino acids, urine organic acids, and ammonia for acutely ill individuals, or urinary amino acids for those with more insidious clinical symptoms, should be performed.