Tyrosine hydroxylase (TH) is a pivotal enzyme in the biosynthesis of catecholamines, such as dopamine, norepinephrine, and epinephrine. It catalyzes the conversion of the amino acid tyrosine to 3,4-dihydroxyphenylalanine (L-DOPA), which is the first and rate-limiting step in this biosynthetic pathway. This conversion is dependent on the cofactor (6R)-L-erythro-tetrahydrobiopterin (BH4) and ferrous iron, with the latter being directly bound to TH and oxidized to Fe3+ by O2. TH is subject to intricate regulation at both transcriptional and post-translational levels. Rapid regulation can occur through end-product inhibition influenced by the phosphorylation status of N-terminal serines, modulating the enzyme's sensitivity to the local concentration of catecholamines. Phosphorylation at specific serine residues, such as Ser40 and Ser31, can enhance TH activity and catecholamine synthesis.
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