MEDICAL HYPOTHESES AND RESEARCH
VOL. 5, No. 1/2, July 2009



A. H. Soloway [2009] Med. Hypotheses Res. 5: 19‒26.


Potential Endogenous Epoxides of Tyrosine: Causative
Agents in Initiating Idiopathic Parkinson Disease?


Albert H. Soloway*

College of Pharmacy, Division of Medicinal Chemistry, The Ohio State University, 500 West
12th Avenue, Columbus, OH 43210, USA


Abstract. The metabolism of tyrosine by tyrosine hydroxylase has the potential for
generating reactive and labile intermediates, such as epoxides, with the capacity for acting as
neurotoxins upon dopaminergic neurons. Those epoxides that are rapidly hydrolyzed by
epoxide hydrolases might not be expected to show toxicity, but those that are shielded and
retained might show such properties. Since the types of epoxides produced would be
determined genetically, this may explain a genetic component being observed in the
causation of Parkinson's disease. Though physiological symptoms observed in Parkinson's
disease have been ameliorated through the administration of levodopa, the drug does not
prevent the continued metabolism of tyrosine and thereby disease progression. Since
metabolism of tyrosine leads to the catecholamines such as dopamine, epinephrine and
norepinephrine, it is relevant to examine the biochemical formation of other catechols, such
as the catechol estrogens, and determine whether comparable intermediates may be
implicated in promoting the disease state.


* Correspondence: Dr. Albert H. Soloway, College of Pharmacy, Division of
Medicinal Chemistry, The Ohio State University, 500 West 12th Avenue, Columbus, OH
43210, USA. E-Mail:
soloway@pharmacy.ohio-state.edu



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