Variance of Microsomal Protein and Cytochrome P450 2E1 and 3A Forms in Adult Human Liver

Details

• Personal Author:
  Lipscomb JC ; Snawder, John E. ; Striley CAF ; Swartout JC ; Teuschler LK
• Description:
  Differences in the pharmacokinetics of xenobiotics among humans makes them differentially susceptible to risk. Differences in enzyme content can mediate pharmacokinetic differences. Microsomal protein is often isolated from liver to characterize enzyme content and activity, but no measures exist to extrapolate these data to the intact liver. Measures were developed from up to 60 samples of adult human liver to characterize the content of microsomal protein and cytochrome P450 (CYP) enzymes. Statistical evaluations are necessary to estimate values far from the mean value. Adult human liver contains 52.9 +/-1.476 mg microsomal protein per g; 2587 +/-1.84 pmoles CYP2E1 per g; and 5237 +/-2.214 pmols CYP3A per g (geometric mean +/-geometric standard deviation). These values are useful for identifying and testing susceptibility as a function of enzyme content when used to extrapolate in vitro rates of chemical metabolism for input to physiologically based pharmacokinetic models which can then be exercised to quantify the effect of variance in enzyme expression on risk-relevant pharmacokinetic outcomes. [Description provided by NIOSH]
• Subjects:
  Digestive System Liver Occupational Health Risk Assessment Safety
• Keywords:
  Author Keywords: Cytochrome P450 Extrapolation Human Liver Humans Liver-cells Liver-function Liver-microsomal-enzymes Liver-microsomal-metabolism Liver-microsomes Pharmacodynamics Pharmacokinetics Physiological-chemistry Physiological-effects Physiological-factors Physiological-function Physiological-response Physiological-testing

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• ISSN:
  1537-6516
• Document Type:
  Text
• Genre:
  Journal Article
• Place as Subject:
  Ohio ; OSHA Region 5
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Division:
  DART - Division of Applied Research and Technology
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Pages in Document:
  45-51
• Volume:
  13
• Issue:
  1
• NIOSHTIC Number:
  nn:20033230
• Citation:
  Toxicol Mech Methods 2003 Jan; 13(1):45-51
• Federal Fiscal Year:
  2003
• Peer Reviewed:
  True
• Source Full Name:
  Toxicology Mechanisms and Methods
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:b5fdf3817932f641e4d9a3d7552b462c1eaee87081bbc152894105beb437c6b304478b3e91bfe834a0f51d665a04d8933690591573eadb708cf2c86f3c6ce8c2
• Download URL:
  https://stacks.cdc.gov/view/cdc/188883/cdc_188883_DS1.pdf
• File Type:
  [PDF - 237.66 KB ]