Tyrosine hydroxylase is the rate limiting step in the biosynthesis of the catecholamine neurotransmitters and is consequently tightly regulated. One of the most important means of regulating the enzyme is the binding of catechol to the active site iron. This results in the enzyme isolated from animal tissue having a very low specific activity. In this study the specificity of iron binding was investigated. Dopamine and norepinephrine were found to be the most potent inhibitors with dissociation constants in the nanomolar range. DOPA, the product of the tyrosine hydroxylase catalyzed reaction, has a dissociation constant almost ten times higher than dopamine's. The substitution of either of the two hydroxyl groups at the 3 and 4 positions on the catechol's aromatic ring increases the dissociation constant by approximately a one hundred fold. The study also demonstrates that the synthetic compounds used to increase the catecholamine levels of patients with Parkinson's disease are relatively poor inhibitors. (Supported in part by NIII grant OM 47291).
|Original language||English (US)|
|State||Published - Dec 1 1997|
ASJC Scopus subject areas
- Molecular Biology