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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 
 
 

Subcellular expression of UGT1A6 and CYP1A1 responsible for propofol metabolism in human brain.

AIM: To observe the subcellular expression of UDP-glucuronosyltransferase 1A6 (UGT1A6) and cytochrome P-450 1A1 (CYP1A1) mRNA in the human brain and investigate the effect of brain on extrahepatic metabolism of propofol. METHODS: Fifteen patients scheduled for craniotomy under propofol anesthesia were selected. Brain tis sue was taken and blood samples from the radial artery and the internal jugular vein were drawn simultaneously. PCR technique was used to detect UGT1A6 and CYP1A1 mRNA in the microsomes and mitochondria. Enzymatic activities were assayed. Blood propofol and propofol-glucuronide concentrations were measured with HPLC and GC, respectively. RESULTS: UGT1A6 mRNA was located mainly in the microsomes, and CYP1A1 mRNA was mainly in the mitochondria. The higher blood concentration of propofol and lower blood concentration of propofol-glucuronide were observed from the radial artery than from the internal jugular vein, respectively. The Km of UGT1A6 and CYP1A1 was (0.74 +/- 0.21) mmol and (548 +/- 50) mmol, respectively. The Vmax was (536 +/- 98) nmol . h-1 . mg-1 and (37 +/- 5) nmol . h-1 . mg-1, respectively. CONCLUSION: The human brain is an important organ for extrahepatic metabolism of propofol. The metabolism occurs within microsomes and mitochondria in brain.[1]

References

  1. Subcellular expression of UGT1A6 and CYP1A1 responsible for propofol metabolism in human brain. Zhang, S.H., Li, Q., Yao, S.L., Zeng, B.X. Acta Pharmacol. Sin. (2001) [Pubmed]
 
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