Phenylketonuria Essay

Phenylketonuria (PKU)

a) Discuss in molecular detail the genetic and biochemical basis for PKU. Phenylketonuria (an inborn error of metabolism) is seen as mutations in the phenylalanine hydroxylase (PAH) gene. PAH changes phenylalanine (essential amino acid) into tyrosine and requires the cofactor tetrahydrobiopterin (BH4), molecular oxygen, and iron to do this. Loss of PAH activity results in increased concentrations of phenylalanine in the bloodstream and toxic concentrations inside the brain, leading to mental retardation. During the hydroxylation of phenylalanine, by phenylalanine hydroxylase (PAH), and when molecular oxygen (O2) and flat iron (Fe2+) can be found, tetrahydrobiopterin (BH4) is oxidized to a 4a-hydroxy-BH4 intermediate. This intermediate can be subsequently regenerated back to BH4 via quinonoid (q) dihydrobiopterin, by the digestive enzymes carbinolamie-4adehydratase (PCD), and by the NADH-dependent dihydropteridine reductase (DHPR). BH4 is usually synthesized via guanosine triphosphate (GTP) by simply three additional enzymes GTP cyclohydrolase I (GTPCH), 6-pyruvoyl-tetrahydropterin synthase (PTPS), and sepiapterin reductase (SR). Variations in genetics coding to get PCD, DHPR, GTPCH, PTPS, and SR result in BH4 deficiency. Therefore , hyperphenylalaninaemia is a result of mutations in genes code for enzymes involved in BH4 biosynthesis or regeneration. The PAH gene consists of 13 exons and the requisite introns. Phenylketonuria occurs when both equally alleles are mutated. The two mutations can occur in any in the exons, in the splice junctions of the intervening introns, or perhaps in other as yet unidentified parts of the gene, such as inside the promoter place. Phenylketonuria is definitely inherited while an autosomal recessive condition. Those who have just one PAH veranderung (eg, father and mother of a kid with phenylketonuria) are service providers and have non-e of the biochemical or scientific characteristics of phenylketonuria. (1) b) Talk about methods currently used to handle PKU. What limitations and difficulties can be found?...

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2 . National Company of Health. Phenylketonuria (PKU): Screening and Management. NIH Consensus Affirmation. 2000. 16-18; 17(3): 1-33.

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4. Leuret O, Barth M, Kuster A, Eyer D, LoГЇc de Parscau, Odent S i9000, Gilbert-Dussardier N, Feillet N, Labarthe N. Efficacy and safety of BH4 before the age of 4 years in patients with mild phenylketonuria. Journal of Inherited Metabolic Disease. 2011. 35 (6). 975-981. Readily available:

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your five. Sarkissian CN, Gamez A. Phenylalanine ammonia lyase, chemical substitution therapy for phenylketonuria, where happen to be we now? Molecular Genetics and Metabolism. june 2006. 86. 139-141. Available: http://www.sciencedirect.com.proxy2.lib.uwo.ca/science/article/pii/S1096719205002386

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