Inhibition of tyrosine hydroxylase by a dopamine neurotoxin, 1-methyl-4-phenylpyridinium ion: depletion of allostery to the biopterin cofactor.

The effect of a dopaminergic neurotoxin, 1-methyl-4-phenylpyridinium ion (MPP+) on the activity of tyrosine hydroxylase was examined using the enzyme sample prepared from the rat striatum. Tyrosine hydroxylase had positive cooperativity to the biopterin cofactor and the Hill's coefficient was calculated as 1.79 +/- 0.23. MPP+ depleted this cooperativity and increased the Km value significantly. In the human brain the concentration of biopterin is unsaturated and the enzyme activity should be profoundly reduced by MPP+. Some of acute symptoms caused by MPP+ may be attributed to the inhibition of tyrosine hydroxylase.