Amino acids metabolic disorders

Tandem mass spectrometry (MS/MS) is applicable to the rapid assay of specific analytes in complex biological fluids (see Chapter 7). In practice, it is usually interfaced to a GC or LC. MS/MS has been used to screen neonates for such amino acid metabolic disorders... 

Amino acid analysis is important not only from a clinical aspect— amino acid metabolism disorders can be fatal if not diagnosed early—but also as the basis for protein and peptide sequencing. Due to the combination of the small amounts of material used in an actual analysis and the lack of chromophores on most amino acid residues, derivatization is common practice. Derivatization may be done prior to either separation or detection. 

Be Pyridoxine, pyridoxal, pyridoxamine Coenzyme in transamination and decarboxylation of amino acids and glycogen phosphorylase role in steroid hormone action Disorders of amino acid metabolism, convulsions... 

Other leukodystrophies are associated with the lysosomal and peroxisomal disorders in which specific lipids or other substances accumulate due to a deficiency in a catabolic enzyme - for example Krabbe s disease, meta-chromatic leukodystrophy (MLD) and adrenoleuko-dystrophy (ALD) [1,2]. (These are discussed in detail in Ch. 40.) Similarly, disorders of amino acid metabolism can lead to hypomyelination - for example phenylketonuria and Canavan s disease (spongy degeneration) [1, 2, 25] (Ch. 40). The composition of myelin in the genetically... 

DISORDERS OF SULFUR AMINO ACID METABOLISM HOMOCYSTINURIA 674... 

Alkaloids such as vinblastine and vincristine are known to bind to the microtubules of the spindle apparatus. They are active agents that influence DNA synthesis and amino acid metabolism. They are also known to reduce mitosis at metaphase. Vinblastine and vincristine also have some immunosuppressive activity. There are many applications of these alkaloids. They have been used in the treatment of Hodgkin s disease, cancers and blood disorders. Vincristine is a basis for the development of clinic agents used to treat cerebral and pulmonary disorders. Vinblastine and vincristine are well-known anficancer agents. 

This is an autosomal recessive disorder that is the most common inborn error of amino acid metabolism, with an incidence of I in 11,000 live births In the United States. 

Amino acids can be separated without prior derivatization on a cation-exchange resin column. The elution buffers are classically lithium citrate buffers with different pH values and salt concentrations, which are applied stepwise. There is usually a programmed increase in column temperature. Consequently, there are numerous variables affecting the separation of the individual amino acids [6]. For the detection of the amino acids, the column effluent is mixed with the ninhydrin reagent. Nowadays there are only very few manufacturers of AAAs left. The considerable cost of purchase and the operation costs are a potential threat to the widespread application of this technique, although it is still considered to be the definitive method for diagnosing disorders of amino acid metabolism. 

Piraud M, Vianey-Saban C, Bourdin C, Acquavica-Bourdain C, Boyer S, Elfakir C, Bou-chu D (2005) A new reversed-phase liquid chromatographic/tandem mass spectrometric method for analysis of underivatized amino acids evaluation for the diagnosis and the management of inherited disorders of amino acid metabolism. Rapid Commun Mass Spectrom... 

Throughout this chapter, we have had occasion to refer to genetic diseases associated with amino acid metabolism. Such defects are characterized by amino acidemias and amino acidurias. The former indicate elevated amino acid levels in serum, whereas the latter indicate their excretion in the urine. A patient may have an amino aciduria without an amino acidemia. This is the case with amino acid transport disorders. It is unusual, however, to have an amino acidemia without amino aciduria. 

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-... 

Piraud, M. et al. Ion-pairing reversed-phase liquid chromatography/electrospray ionization mass spectrometric analysis of 76 underivatized amino acids of biological interest a new tool for the diagnosis of inherited disorders of amino acid metabolism. Rapid Commun. Mass Spectrom. 2005, 19, 1587—1602. 

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. 

Table 55-2 shows a summary of known disorders of amino acid metabolism and transport, including information about their incidence, major clinical features and biochemical patterns, availabitity of prenatal diagnosis and newborn screening, and association with sudden unexpected death. Several of these disorders are discussed next. 

Disorders of Branched Chain Amino Acid Metabolism... 

Disorders of Sulfur Amino Acid Metabolism Hypermethioninem... 

TABLE 55-2. CtiniGal and Laboratory Characteristics of Disorders of Amino Acid Metabolism—Continued i... 

PIHH syndrome. 238970 Mitochondrial ornithine transporter MisceUaneous Disorders of Amino Acid Metabolism <1 100,000. Mental retardation,. seizures, pyramidal signs, compromised. sense of vibration. . v ... 

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