Journal article

Tyrosine hydroxylase activity is regulated by two distinct dopamine-binding sites.

Sarah L Gordon, Noelene S Quinsey, Peter R Dunkley, Phillip W Dickson

J Neurochem | Published : 2008

Abstract

Tyrosine hydroxylase (TH), the rate-limiting enzyme in the biosynthesis of the catecholamines dopamine, noradrenaline and adrenaline, is regulated acutely by feedback inhibition by the catecholamines and relief of this inhibition by phosphorylation of serine 40 (Ser40). Phosphorylation of serine 40 abolishes the binding of dopamine to a high affinity (K(D) < 4 nM) site on TH, thereby increasing the activity of the enzyme. We have found that TH also contains a second low affinity (K(D) = 90 nM) dopamine-binding site, which is present in both the non-phosphorylated and the Ser40-phosphorylated forms of the enzyme. Binding of dopamine to the high-affinity site decreases V(max) and increases the..

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