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== Phenylketonuria == L-Tyrosine is the precursor to neurotransmitters such as epinephrine, dopamine, and serotonin. It is essential that L-phenylalanine is converted into L-tyrosine by the hydroxylation reaction. In order for this conversion to be successful, the enzyme phenylalanine hydroxylase needs to be able to function properly. PAH depletion or mutation leads to excessive accumulation of toxic L-Phe levels. However, normal physiological plasmatic levels of L-phenylalanine are less than 120 micromolar. When the enzyme PAH doesn’t function currently, the  autosomal recessive metabolic disorder Phenylketonuria (PKU) occurs. PKU is a congenital disorder characterized by excessive amounts of L-phenylalanine that buildup to neurotoxic amounts leading to cognitive disability and neurological impairment, including profound mental retardation, seizures, microcephaly, and delayed development. The severity of PKU is dependent upon the severity of the enzyme’s mutation. PAH mutations result in reduced enzyme activity and stability and some alter its oligomeric state. These mutations spread throughout the 3D structure, but most are located in the catalytic domain. Loss of enzymatic function is caused mainly by folding defects that lead to decreased protein stability.