Phenylketonuria structural proteins

Phenylalanine (Phe or F) (2-amino-3-phenyl-propanoic acid) is a neutral, aromatic amino acid with the formula HOOCCH(NH2)CH2C6H5. It is classified as nonpolar because of the hydrophobic nature of the benzyl side chain. Tyr and Phe play a significant role not only in protein structure but also as important precursors for thyroid and adrenocortical hormones as well as in the synthesis of neurotransmitters such as dopamine and noradrenaline. The genetic disorder phenylketonuria (PKU) is the inability to metabolize Phe. This is caused by a deficiency of phenylalanine hydroxylase with the result that there is an accumulation of Phe in body fluids. Individuals with this disorder are known as phenylketonurics and must abstain from consumption of Phe. A nonfood source of Phe is the artificial sweetener aspartame (L-aspartyl-L-phenylalanine methyl ester), which is metabolized by the body into several by-products including Phe. The side chain of Phe is immune from side reactions, but during catalytic hydrogenations the aromatic ring can be saturated and converted into a hexahydrophenylalanine residue. ... 

Figure 23.31. Structure of One Subunit of Phenylalanine Hydroxylase. Mutations in the genes encoding this enzyme cause phenylketonuria. More than 200 point mutations have been identified in these genes. The positions of five mutations affecting the active site (blue), the biopterin-binding site (red), and other regions of the protein (purple) are indicated as colored spheres.

Nevertheless, all of this amazing functionality displayed by natural proteins seems to be based on a simple fact a complex and completely defined primary structure. In living cells, protein biosynthesis is carried out with an absolute control of the amino acid sequence, from the first amino acid to the last with a complete absence of randomness. In fact, the need for this absolute control is dramatically clear in some genetic disorders in which the lack or a substitution of a single amino acid in the whole protein leads to a complete loss of the original function, which can have dramatic consequences in some cases such as falciform anemia (sickle cell anemia), phenylketonuria, and cystic fibrosis [7]. 

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