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


CONCLUSIONS
The human brain is an important organ for extrahepatic metabolism of propofol. The metabolism occurs within microsomes and mitochondria in brain.
Zhang
S H
SH
Department of Anesthesiology, Union Hospital, Huazhong University of Science & Technology, Wuhan 430022, China. zhangshv@public.wh.hb.cn
Li
Q
Q
Yao
S L
SL
Zeng
B X
BX
D000328:Adult; D000368:Aged; D018686:Anesthetics, Intravenous / Q000378:metabolism*; D001921:Brain / Q000201:enzymology* / Q000378:metabolism; D019363:Cytochrome P-450 CYP1A1 / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D005260:Female; D014453:Glucuronosyltransferase / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008297:Male; D008861:Microsomes / Q000201:enzymology / Q000378:metabolism; D008875:Middle Aged; D008928:Mitochondria / Q000201:enzymology / Q000378:metabolism; D015742:Propofol / Q000378:metabolism*; D013347:Subcellular Fractions
D018686:Anesthetics, Intravenous; D019363:Cytochrome P-450 CYP1A1; C110655:UDP-glucuronosyltransferase, UGT1A6; D014453:Glucuronosyltransferase; D015742:Propofol