
Substrate Oxidation by Cytochrome P450 Enzymes 
239 
microsomal preparations. Drug Metab. Dispos. 
21,
 242-248. 
200.
 Sadeque, A.J.M., M.B. Fisher, K.R. Korzekwa, F.J. 
Gonzalez, and A.E. Rettie (1997). Human 
CYP2C9 and CYP2A6 mediate formation of the 
hepatotoxin 4-ene-valproic acid. J. Pharmacol 
Exp.
 Ther. 283, 698-703. 
201.
 Fisher, M.B., S.J. Thompson, V Ribeiro, M.C. 
Lechner, and
 A.E.
 Rettie (1998). P450-catalyzed in-
chain desaturation of valproic acid: Isoform selec-
tivity and mechanism of formation of A^-valproic 
acid generated by baculovirus-expressed CYP3A1. 
Arch.
 Biochem. Biophys. 356, 63-70. 
202.
 Rettie, A.E., PR. Sheffels, K.R. Korzekwa, FJ. 
Gonzalez, R.M. Philpot, and T.A. Baillie (1995). 
CYP4 isozyme specificity and the relationship 
between co-hydroxylation and terminal desatura-
tion of valproic acid. Biochemistry 34, 7889-7895. 
203.
 Rettenmeier,
 A.W.,
 W.P Gordon, K.S. Prickett, R.H. 
Levy, J.S. Lockard, K.E. Thummel et al. (1986). 
Metabolic fate of valproic acid in the rhesus mon-
key. Formation of a toxic metabolite, 2-n-propyl-4-
pentenoic acid. Drug
 Metab.
 Dispos. 14, 443^53. 
204.
 Pennanen, S., A. Kojo, M. Pasanen, J. Liesivuori, 
R.O.
 Juvonen, and H. Kumulainen (1996). CYP 
enzymes catalyze the formation of a terminal 
olefin from 2-ethylhexanoic acid in rat and human 
liver. Hum. Exp. Toxicol. 15, 435-442. 
205.
 Behrouzian, B. and PH. Buist (2002). Fatty acid 
desaturation: Variations on an oxidative theme. 
Curr. Opin. Chem. Biol 6, 577-582. 
206.
 Obach, R.S. (2001). Mechanism of cytochrome 
P4503A4- and 2D6-catalyzed dehydrogenation of 
ezlopitant as probed with isotope effects using 
five deuterated analogs. Drug
 Metab.
 Dispos. 29, 
1599-1607. 
207.
 Hold, K.M., N.S. Sirisoma, and IE. Casida (2001). 
Detoxification of a- and P-thujones (the active 
ingredients of absinthe): Site specificity and species 
differences in cytochrome P450 oxidation in vitro 
and in
 vivo.
 Chem.
 Res. Toxicol 14, 589-595. 
208.
 Hata, S., T. Nishino, M. Komori, and H. Katsuki 
(1981).
 Involvement of cytochrome P-450 in A^^-
desaturation in ergosterol biosynthesis in yeast. 
Biochem. Biophys. Res. Commun. 103, 272-277. 
209.
 Kelly, S.L., D.C. Lamb, B.C. Baldwin, A.J. 
Corran, and D.E. Kelly (1997). Characterization 
of Saccharomyces cerevisiae
 CYP61,
 sterol A22-
desaturated, and inhibition by azole antifungal 
agents. J. Biol Chem. 272, 9986-9988. 
210.
 Skaggs, B.A., J.F Alexander, C.A. Pierson, K.S. 
Schweitzer, K.T. Chun, C. Koegel et al (1996). 
Cloning and characterization of the Saccharomyces 
cerevisiae C-22 sterol desaturase gene, encoding a 
second cytochrome P-450 involved in ergosterol 
biosynthesis. Gene 169, 105-109. 
211.
 Lamb, D.C, S. Maspahy, D.E. Kelly, N.J. 
Manning, A. Geber, J.E. Bennett et al (1999). 
Purification, reconstitution, and inhibition of 
cytochrome P-450 sterol A^^-desaturase from the 
pathogenic fungus Candida glabrata. Antimicrob. 
Agents Chemother. 43, 1725-1728. 
212.
 Rodrigues, C.M.P, B.T. Kren, C.J. Steer, and 
K.D.R. Setchell (1996). Formation of D22-bile 
acids in rats is not gender specific and occurs in 
the peroxisome. J. Lipid Res. 37, 540-550. 
213.
 Nagata, K., D.J. Liberato, J.R. Gillette, and H.A. 
Sasame (1986). An unusual metabolite of testos-
terone: 17p-hydroxy-4,6-androstadiene-3-one. Drug 
Metab.
 Dispos. 14, 559-565. 
214.
 Aoyama, T., K. Korzekwa, K. Nagata, J. Gillette, 
H.V Gelboin, and FJ. Gonzalez (1989). cDNA-
directed expression of rat testosterone 7a-hydrox-
ylase using the modified vaccinia virus, 
T7-RNA-polymerase system and evidence for 
6n-hydroxylation and A^-testosterone formation. 
Eur J. Biochem. 181, 331-336. 
215.
 Korzekwa, K.R., W.K Trager, K. Nagata, A. 
Parkinson, and J.R. Gillette (1990). Isotope effect 
studies on the mechanism of the cytochrome P-
450IIA1-catalyzed formation of A^-testosterone 
from testosterone. Drug Metab. Dispos. 18, 
974-979. 
216.
 Chadwick, R.W., L.T. Chuang, and K. Williams 
(1975).
 Dehydrogenation: A previously unre-
ported pathway of lindane metabolism in mam-
mals.
 Pestic. Biochem. Physiol 5, 575-586. 
217.
 Mochizuki, H., K. Suhara, and M. Katagiri (1992). 
Steroid 6(3-hydroxylase and 6-desaturase reactions 
catalyzed by adrenocortical mitochondrial P-450. 
J. Steroid
 Biochem.
 Mol Biol 42,
 95-101. 
218.
 Boyd, D.R., N.D. Sharma, R. Agarwal, R.A.S. 
McMordie, J.G.M. Bessems, B. van Ommen et al 
(1993).
 Biotransformation of
 1,2-dihydronaphtha-
lene and 1,2-dihydroanthracene by rat liver 
microsomes and purified cytochromes P-450. 
Formation of arene hydrates of naphthalene and 
anthracene. Chem. Res. Toxicol 6, 808-812. 
219.
 Adams, J.D., H. Yagi, W. Levin, and D.M. Jerina 
(1995).
 Stereo-selectivity and regio-selectivity in 
the metabolism of 7,8-dihydrobenzo[a]pyrene by 
cytochrome P450, epoxide hydrolase and hepatic 
microsomes from 3-methylcholanthrene-treated 
rats.
 Chem. Biol Interact. 95, 57-77. 
220.
 Kaminsky, L.S., M.J. Fasco, and F.P Guengerich 
(1980).
 Comparison of different forms of purified 
cytochrome P-450 from rat liver by immunologi-
cal inhibition of
 regio-
 and stereoselective metab-
olism of warfarin. J. Biol Chem. 255,
 85-91. 
221.
 Vyas, K.R, PH. Kari, S.R. Prakash, and D.E. 
Duggan (1990). Biotransformation of lovastatin. 
II.
 In vitro metabolism by rat and mouse liver