Professor, Eppley Institute
Department of Biochemistry and Molecular Biology
Environmental Health and Toxicology
Ph.D. - Northwestern University, 1971
Organophosphorus pesticides including chlorpyrifos, dichlorvos, parathion, malathion, and diazinon are used in agriculture to protect crops from insects. Organophosphorus pesticides are similar to military nerve agents in their mechanism of action. Both types of compounds irreversibly inhibit acetylcholinesterase, an enzyme critical for nerve impulse transmission. Insects die when their acetylcholinesterase is inhibited. Humans exposed to doses high enough to inhibit 80% of their acetylcholinesterase suffer respiratory failure and death. Lower doses cause impaired vision, lacrimation, headache, numbness, twitching muscles, and gastrointestinal distress. After acute symptoms have disappeared an individual may suffer depression for months or years.
Epidemiologist have linked low dose exposure to illnesses such as non-Hodgkin’s lymphoma, Alzheimer disease, Parkinson’s disease, and chronic depression. Low dose exposure is difficult to detect by standard enzyme activity measurement because baseline activities in individuals vary over a broad range. Our laboratory has developed a mass spectrometry method for measuring low dose exposure. Our method is based on the knowledge that butyrylcholinesterase in blood is highly reactive with organophosphorus compounds. The active site serine 198 of human butyrylcholinesterase makes a covalent bond with organophosphorus compounds to make a stable adduct that can be detected by mass spectrometry. We have found that other proteins also make a covalent bond with organophosphorus compounds. For example, albumin in blood makes a stable adduct on tyrosine 411.
Our goal is to identify the mechanism by which low dose exposure to organophosphorus compounds leads to disease. We expect to achieve this goal by identifying the set of proteins modified by exposure to organophosphorus compounds. The major tool for this effort is mass spectrometry.
E-Mail: Oksana Lockridge