INTRODUCTION :
Phenylketoneuria also designated as PKU is defined as an inborn error of metabolism due to deficiency of the enzyme phenylalanine hydroxylase (PAH). This is a rare genetic condition in which occurs inability to metabolise or break down the essential amino acid phenylalanine to tyrosine due to enzyme deficiency. Amino acids are considered as the building blocks of protein and so does this amino acid i.e. phenylalanine. Phenylalanine is an essential amino acid and hence, finds a role in protein synthesis in our body. Certain sources of phenylalanine include most of the proteins and some artificial sweetners. The enzyme phenylalanine hydroxylase (PAH) helps in the breakdown of phenylalanine into simpler compounds that can be easily
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• Mild or even moderate phenylketonuria : Phenylalanine tolerance can range from 250 to 400 mg per day.
THE PHENYLALANINE HYDROXYLASE (PAH) ENZYME :
The human phenylalanine enzyme is expressed in liver as well as in the kidney. This enzyme is involved in the conversion of phenylalanine to tyrosine. The phenylalanine hydroxylase enzyme has two forms among which tetrameric form is active and dimeric form is inactive. Additionally, there exists three domains of the enzyme namely C- terminal catalytic domain, an N- terminal regulatory domain and a tetramerization domain. Tetrahydrobiopterin (BH4) acts as a cofactor for the enzyme activity. Hence, the regulatory action by PAH enzyme involves activation by the presence of the amino acid phenylalanine, inhibition by the cofactor Tetrahydrobiopterin (BH4) and activation of the enzyme by phosphorylation. Cyclic adenosine monophosphate (cAMP) – dependent protein kinase helps in the phosphorylation of the amino acid serine that is present on the 16 position of the regulatory domain of the enzyme. This in turn helps in maintaining the activity of the enzyme by reducing the concentration of the phenylalanine