Kinetics of substrate hydrolysis and inhibition by mipafox of paraoxon-preinhibited hen brain esterase activity.

Details

• Personal Author:
  Abou-Donia MB ; Carrington CD
• Description:
  The kinetics of substrate hydrolysis and the kinetics of inhibition by mipafox (371868) of the paraoxon (311455) resistant esterases in a membrane fraction of White Leghorn hen brain were investigated. Paraoxon was added to homogenized hen brain to a concentration of 40 micromoles and the homogenate was processed with a series of centrifugation procedures. Paraoxon preinhibited hen brain was found to have both neurotoxicant sensitive and insensitive esterase components. Kinetic parameters for the hydrolysis of phenyl- valerate (PV) and phenyl-phenylacetate (PPA) were as follows: neurotoxic esterase (NTE) Michaelis constant (Km) values were found to be about 0.0014 and 0.00016 Molar (M), respectively, at 37 degrees-C and 0.0024M for PV at 25 degrees-C. NTE kinetic constants for mipafox with either PV or PPA as substrate were determined to be Km=0.00018M and the phosphorylation constant (K2)=1.1min(-1) at 37 degrees-C; at 25 degrees-C, Km=0.0006M and K2=0.7min(-1) for PV only. The 25 degree-C data was analyzed with a two component model with or without formation of Michaelis complex on NTE, or a three component model without formation of Michaelis complex. The authors report that the Michaelis model fit the data significantly better and conclude that the higher apparent Ki values at low mipafox concentrations are due to formation of Michaelis complex at high concentrations. The authors also conclude that if mipafox competes directly for the active site of NTE, then the much greater inhibitory power of mipafox must be due to a much greater K2 for mipafox than for paraoxon. [Description provided by NIOSH]
• Subjects:
  Enzymes Esters Halothane Hydrocarbons Laboratories Nervous System Occupational Health Phenol Phosphorous Compounds Safety
• Keywords:
  Enzyme-activity Enzyme-inhibitors Fluorinated-hydrocarbons Halogenated-hydrocarbons Halogenated-phosphates Laboratory-animals Neurotoxicity NIOSH-Grant NIOSH-Publication Nitrophenols Organophosphorous-compounds Phenols

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• ISSN:
  0264-6021
• Document Type:
  Text
• Funding:
  Grant
• Genre:
  Journal Article
• Place as Subject:
  North Carolina ; OSHA Region 4
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  236
• Issue:
  2
• NIOSHTIC Number:
  nn:00163207
• Citation:
  Biochemical J 1986 Jun; 236(2):503-507
• Contact Point Address:
  Mohamed B. Abou-Donia, Department of Pharmacology, Duke University Medical Center, Durham, NC 27710, U.S.A.
• CAS Registry Number:
  Mipafox (CAS RN 371-86-8) ; Paraoxon (CAS RN 311-45-5)
• Federal Fiscal Year:
  1986
• Performing Organization:
  Pharmacology Duke University Medical CenterBox 3813 Durham, NC 27710
• Peer Reviewed:
  True
• Start Date:
  19840601
• Source Full Name:
  Biochemical Journal
• End Date:
  19881031
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:f3c99ee46cba13ad45e001ecb2f656299707930f012cfed401132933b716178425a9b80a2a10d66fce2d3d423f4e42f6215593f1b03f4c04b763280392203b64
• Download URL:
  https://stacks.cdc.gov/view/cdc/184985/cdc_184985_DS1.pdf
• File Type:
  [PDF - 957.21 KB ]