Phenylketonuria Research Paper

Introduction
Phenylketonuria (PKU) is an autosomal recessive inherited condition[1] which causes a build up in the concentration of phenylalanine (Phe) in the blood. A deficiency in phenylalanine hydroxylase (PAH), which is found in the liver[2-3] causes this build up as this is the enzyme which catalyses the reaction which adds a hydroxyl group to Phe to form tyrosine (Tyr).[1]

Due to the congenital nature of this condition, it is tested for just after the time of birth by testing the a blood sample taken from a heel prick test[4] which was introduced by Robert Guthrie in the 1960s.[1, 3] Disorders which are caused by the deficiency of PAH can be categorised into 4 distinct types[5]; Classic PKU, Moderate PKU, Mild PKU and Mild Hyperphenylalaninaemia …show more content…
For example, in the UK, the incidence is 1:14,300 whereas in Finland the incidence is 1:200,000[3]. The low incidence in Finland is thought to be related negative founder effect[3], where the original population had an extremely low incidence of PKU. In Turkey however there is a very high incidence with the proportion of affect to non affected being 1:2,600, his is thought to be because of consanguinity.[3]

Reactions within Cell
Converting Phe to Tyr is a hydroxylation reaction which occurs in humans within the liver (Figure 2). For this reaction to occur, there are other substances which need to be present, which include PAH, Oxygen (O2)[1], Fe2+, the cofactor tetrahydrobiopterin (BH4)[3] and enzymes which re-generate BH4, of which examples are dihydropteridine reductase (DHPR) and 4α-carbinolamine dehydratase (PCD)[1]. During the hydroxylation of Phe, BH4 is oxidised to form a 4α-hydroxy-BH4 intermediate[1], which is then converted back to BH4 by the enzymes PCD and DHPR[1](Figure 2). It could be argued that BH4 is as important as PAH in the conversion of Phe to Tyr, so a fault in the synthesis or regeneration of this could cause …show more content…
Transamination is an example of of one of these reactions. In the presence of the enzyme α-Ketoglutarate, Phe can be converted to Phenylpyruvate, which can then be further converted into other various phenyl containing compounds which can be excreted via urine.[3] Another example of an alternative reaction is the decarboxylation of Phe. In this reaction, Phe is converted (via various steps) to Phenylacetylglutamate which can also be removed via the urine.[3] Although these reactions can convert some Phe into other products, they do not remove a large enough amount, so a build up of Phe, when PAH is deficient will still

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