Project: Research project

Project Details


The enzyme tyrosine hydroxylase catalyzes the rate-limiting step in the
biosynthesis of catecholamine neurotransmitters. The major aim of the
experiments described in this proposal is to characterize the following three
biochemical events which rapidly modify tyrosine hydroxylase activity by
changing the affinity of the enzyme for its pterin cofactor: 1) anionic
phospholipids, 2) enzymatic phosphorylating conditions, and 3) partial
proteolysis. Each of these events can activate tyrosine hydroxylase; a
comparative study will yield information concerning whether or not the
activations occur via a common or through distinct mechanisms.
One class of anionic phospholipids, the phosphoinositides, have the remarkable
ability to either stimulate or inhibit tyrosine hydroxylase, depending upon
preincubation conditions. The phosphoinositides comprise a very small portion
of the total phospholipid in nervous tissue, but they are the only class of
phospholipids which turn over rapidly in response to cellular stimuli, e.g.,
depolarization. Experiments have been designed to characterize the mechanism(s)
of how the phosphoinositides may modulate tyrosine hydroxylase activity, using
both purified enzyme preparations and synaptosomal or neuroblastoma cell culture
preparations where in situ tyrosine hydroxylation may be measured.

In the course of the purification of tyrosine hydroxylase, a factor has been
isolated which prevents the phosphatidylinositol-induced inactivation of this
enzyme. Experiments have been designed to isolate and characterize this
potentially physiologically important endogenous modulator of tyrosine
hydroxylase activity.
Effective start/end date1/1/901/1/90


  • National Institute of General Medical Sciences


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