Amino acid clinical implications

In addition to epilepsy, neuronal death due to the toxic effects of glutamate has also been implicated in cerebral ischaemia associated with multi-infarct dementia and possibly Alzheimer s disease. With the plethora of selective excitatory amino acid receptor antagonists currently undergoing development, some of which are already in clinical trials, one may expect definite advances in the drug treatment of neurodegenerative disorders in the near future. 

Metabolites from cyanobacteria are generally of amino acid or polyketide origin and frequently show potent biological activity. The series of dolastatin metabolites, exemplified by dolastatin-10 (Structure 2.18), are linear peptides which show potent cytotoxic activity and are of clinical interest as anti-tumour agents. Originally isolated in very low yield from the Indian Ocean sea hare Dolabella auricularia, dolastatins are now known to be cyanobacterial products.43,44 The discovery of a microbial source for these pharmaceutically important compounds will facilitate study of their biosynthesis and could potentially lead to the production of structural analogues by provision of modified biosynthetic precursors to the cultivar. As discussed below and in Section VI, toxic secondary metabolites from cyanobacteria have often been implicated in the chemical defenses of sea hares.45"17... 

It is important to note that, while PA intake must be significantly reduced in affected individuals, PA is still an essential amino acid and cannot be completely eliminated from the diet. As such, growth rate and PA levels need to be monitored regularly. Unfortunately, as clearly identified by Mrs. Urick, these diets are often expensive and universally unpalatable. As such, compliance is frequently a clinical issue (Bodamer, 2003 Scriver, 2000). In this case, the physician is left with several questions Was it appropriate for Mrs. Urick to discontinue her diet What are the implications, if any, for her unborn baby and Will she or her baby be a candidate for BH4 therapy ... 

The O2P, integrin is expressed in a variety of cell types. In cells of haematopoietic lineage, expression is restricted to megakaryocytes and platelets. On endothelial cells and fibroblasts and many epithelial cell types, OjP, additionally binds to laminin" The echovirus 1, a non-enveloped RNA-virus implicated in febrile illness and viral meningitis, binds to Ojp," . OjP, bears the clinically important Br(a) and Br(b) alloantigenic determinants, which can result in antibody-mediated platelet destruction. A single base change results in a substitution of Lys in Br(a) to Glu in Br(b) at amino acid residue 505". ... 

The major important organic electrolytes and nonelectrolytes transported by epithelial cells include sugars, amino acids, nucleosides, organic cations, and organic anions. Transport systems have significant implications for the absorption, distribution, elimination, and pharmacokinetic properties of many clinically important drugs. The major epithelial tissues... 

Figure 43-3 Thiopurine S-methyltransferase (TPMT) allele variants. Gray boxes represent mutations that result in amino acid changes.TPMT 4 is a 5 splice site mutation for exon 10 that does not alter an amino acid. White boxes represent untranslated regions. Black boxes represent exons in the open reading frame.The dashed box represents exon 2, which was detected in 6.25% of human liver cDNAs during initial evaluation. (From McLeod HL, Siva C. The thiopurine S-mefhy/transferose gene locus—implications for clinical pharmacogenomics. Pharmacogenomics 2002 3 89-98. Reproduced by permission from future Medicine Ltd [London].)...

Stability of BNP immunoreactivity is compromised in whole blood collected in glass tubes versus plastic and siliconized tubes. This has been described by all assay manufacturers, with 30% to 80% loss of immunoreactivity in glass after 4 to 8 hours. Further, proBNP has been shown to be more stable than its metabolized form of BNP, which is the 32-amino acid form measured by BNP immunoassays. Further studies regarding the immunoreactivity of proBNP and thus half-life differences are needed by each BNP commercial assay to better elucidate the clinical utility if any for proBNP in CHF patients. Imprecise implications also should be better understood and studied regarding different assays. Quality specifications are available for BNP... 

Harper AE. 1976. Protein and amino acids in the regulation of food intake. Hunger Basic Mechanisms and Clinical Implications. Novin D, Wyrwicka W, Bray G, editors. New York Raven Press pp. 103-113. 

BCAAs) is superior to standard protein solutions that are higher in aromatic amino acids (AAAs)J Metabolism of AAAs into false neurotransmitters that penetrate the blood-brain barrier (which itself may be perturbed in patients with HE) has been implicated as a cause of HE. A number of clinical trials have evaluated the use of BCAAs in the treatment of HE, with conflicting results. Reviews of these trials have also arrived at different conclusions. BCAAs may have a role in the malnourished patient with cirrhosis who is intolerant of protein supplementation, but the current data do not justify routine use of BCAAs for the treatment of HE. Impairment of dopaminergic transmission has also been proposed to cause HE, but trials with bromocriptine and levodopa failed to provide any benefit and are not recommended. ... 

The first and most widely used MS/MS test developed for clinical diagnosis is the acylcarnitine profile [3]. This chapter will therefore focus primarily on this test and its diagnostic implications. Other valuable tests have recently been developed or are in the process of development by MS/ MS, some of which are also discussed in this section. These include assays for free and total carnitine [17], selected amino acids including phenylalanine and tyrosine [4], methionine [5], homocysteine [6] and sulfocysteine, and for selected pyrimidines [7] and acylglycines [8]. Methods for bile acids [9, 10], steroids, plasmalogens [11], sphingolipids and phospholipids have also recently been reported. Although alternative methods are available for most of these tests, none can match the quantitative precision and rapid turn-around time of MS/MS. 

Young, V. R., et al. 1989. A theoretical basis for increasing current estimates of the amino acid requirements in adult man, with experimental support. American Journal of Clinical Nutrition 50 80-92 Young, V. R., and P. L. Pellett. 1990. Current concepts concerning indispensable amino acid needs in adults and their implications for international nutrition planning. Food and Nutrition Bulletin 12 289-300 Pellett, P. L. 1990. Protein requirements in humans. American Journal of Clinical Nutrition 51 723-737 FAO/WHO. 1991. Protein Quality Evaluation. Rome FAO. 

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