Ortiz de Montellano Paul R.(Ed.) Cytochrome P450. Structure, Mechanism, and Biochemistry
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Index
Cyp4f37, 533
Cyp4f39, 533
CYP4V2, 379, 437
CYP4X1,379,437
CYP4Z1,379,437
CYP5A1 (thromboxane synthase)
active site, 439
disease links, 383
inhibition, 439
polymorphism, 438
properties, 533
reaction, 379, 438
regulation/induction, 438
substrates, 438, 439
tissue location, 379, 437, 438
CYP7A1,327
actives site, 441
content in tissues, 439
disease links, 383
inhibition, 441,637
instability of, 440
phosphorylation, 440
polymorphisms, 440
regulation/induction, 439, 440, 622
substrates, 439, 440, 622, 631, 637
tissue location, 379, 439
CYP7B1
disease links, 383
substrates, 441
tissue location, 379, 441
CYP8A1 (prostacyclin synthase)
active site, 442
disease links, 383, 443
gene organization, 442
inhibition, 442
membrane topology, 442
polymorphism, 442
properties, 533
reaction catalyzed, 379, 438
substrates, 441,442
tissue location, 379, 442
CYP8B1
regulation, 443
substrates, 443, 622, 631
tissue location, 379, 443
CYPllAl (P450scc),211
active site, 445
adrenodoxin interaction, 445
CO sensitivity, 248
deficiency, 446
disease links, 383
inhibition,
271,
445
interaction with reductase, 135, 136
polymorphism, 445
reactions, 286
regulation, 445
CYPllAl i?450scc)
contd.
substrates, 445
tissue location, 379, 443
CYP11B1(P45011P)
active site, 447
adrenodoxin interaction, 447
disease links, 383
inhibition, 249, 447
polymorphism, 446
redox partners, 135
regulation, 446
substrates, 446, 447
tissue location, 379, 446
CYPllB2(P450aldo)
active site, 448
disease links, 383
inhibition, 448
regulation, 447
substrate, 448
tissue location, 379, 447
CYP17A1
active site, 449, 450
disease links, 383, 450
effect of cytochrome b5, 134, 448, 449
fusion protein with reductase, 133
inhibition, 292, 450
mechanism, 216, 449
mutants, 217
pH dependence of products, 217
phosphorylation, 449
polymorphism, 449, 450
regulation, 449
substrates, 215, 449
tissue location, 379, 448
CYP19A1 (aromatase)
active site, 452
disease linked to it, 289, 383, 452
gene organization, 451
inhibition of, 248, 250, 271, 286, 287, 289, 452
isotope effects in, 218
polymorphisms,
451,
452
reaction, 6, 217, 218, 219, 451, 452
regulation, 451
substrates, 452
tissue location, 379, 451
CYP20A1,379,452
CYP21A2
active site, 453
disease links, 383, 453
inhibition, 386, 453
regulation/induction, 386, 453
role in drug metabolism, 386
substrates, 386, 453
tissue location, 379, 453
CYP24A1
active site, 455
Index
CYP24A1
contd.
disease links, 383
inhibition, 455
regulation, 454, 455
substrates, 380, 455
tissue location, 379, 454
CYP26A1
substrate, 456
tissue location, 379, 456
CYP26B1
substrate, 456
tissue location, 379, 456
CYP26C1
tissue location, 379,456
CYP27A1
active site, 458
disease links, 383
polymorphisms, 456
regulation, 440, 456
substrates, 457
tissue location, 379,456
CYP27B1
active site, 460
disease links, 383
gene organization, 459
mutations, 459, 460
regulation, 459
substrates, 460
tissue location, 379,459
CYP27C1,379,460
CYP39A1,379,460
CYP46A1,379,461
CYP51 (sterol 14-demethyIase), 555, 590, 594,
601,
602
active site, 462, 609
in azole resistance, 607-609
mutations leading to, 608, 609
complementation by, 558
and cytochrome bj, 462
fusion protein with ferredoxin, 588, 592, 594
inhibition, 120,250,603
knockout in bacteria, 592, 604
phylogram of
sequences,
590, 591, 596, 597
reaction, 217, 217,
219-221,
379, 585-587
regulation, 461
structure of, 88, 110, 107, 183,462
substrates, 461
tissue location, 379,461
CYP52, 602
CYP54, 603
CYP55Al,5eeP450^^^
CYP56, 602
dityrosine formation, 603
CYP57,
603
dityrosine formation, 601
CYP58,
603
CYP59, 603
CYP61,602,604
22-desaturation, 586, 592, 601-603
CYP64, 603
CYP71,
9, 555-557, 562-569
CYP72, 555, 569
CYP73A5,
555, 557
CYP74A1,555
CYP74B2, 555
CYP75B 1,555
CYP79, 555-557, 562-566, 573, 574
CYP80, 555
CYP83,
555, 574
CYP84A1,555
CYP85,
555, 558, 560
CYP86A1,555
CYP86A8, 555
CYP88A, 225, 226, 555
CYP90A1,
555, 558,560
CYP90B1,555,560
CYP93C, 226, 227, 555, 571
CYP98A3,
555
CYP101,5eeP450,^
CYP102,
see
P450BJ^.3
CYP105,
595, 596, 598-601
CYP108,5eeP450j^^p
CYP107A1
crystal structure, 183
hydrogen bonding network, 164
CYP107, 599, 601
CYP116,595
CYP119,596
complex with imidazoles, 100
crystal structure, 88, 91, 100, 183, 601
reaction with peroxides, 3, 161
thermal stability, 91, 601
CYP121,592,594,598
CYP122, 599
CYP123,
594
CYP124, 594
CYP125,
592, 594, 596, 601
CYP126, 594
CYP128,
594, 598
CYP129, 599
CYP130,594
CYP131,599
CYP132,594, 598
CYP135,594,598
CYP136,594
CYP137, 594, 598
CYP138,
594
CYP139, 594, 598
CYP140. 594, 598
CYP141.594,598
CYP142, 594
CYP143,
594, 598
CYP144, 594
670
Index
CYP151,598
CYP152A1
reaction, 170
structure, 170
CYP154, 599,601
crystal structure, 106, 110, 183, 600
CYP156,599,601
CYP157, 599, 601
CYP158,600,601
CYP
160,
599
CYP161,599
CYP
162,
599
CYP163,
599
CYP164, 592, 594, 598
CYP
170,
590,
592,
594, 596, 599
gene deletion of, 599
CYP171,599,601
CYP 175 A 1,596
structure, 92, 601
CYP176Al,5e^P450cin
CYP178,601
CYP180A1,598,601
CYP181,601
CYP504, 586, 587
CYP505,
115,603
fusion protein, 603
CYP701A3,
555
CYP710,592
Cysteine ligand, 2, 7, 50, 158
bondlength, 57, 59, 61
effect on iron, 48, 52, 61, 183, 190, 248
in P420, 265
hydrogen bonding to, 48, 89, 186
"push" effect, 48, 52-54, 58, 63, 155
and spin state, 48, 157
Cytochrome b5
alternate P450 reductase in yeast, 605, 606
apocytochrome b5, 134,409, 413, 426, 449
complex with P450, 134, 135
concentration of, 646
electron transfer to P450, 115
and hemoglobin, 134
interaction with P450 reductase, 120, 133, 134
and lipid biosynthesis, 133, 134
properties of, 133, 134
redox potential, 134
role in vivo, 119, 134
role in individual P450s, 403, 409, 413, 426, 449
and uncoupling, 134, 184
Cytochrome b5 reductase, 119, 133, 134, 605, 606
Cytochrome c, 120
crosslinking to P450 reductase, 129
inapoptosis, 116
Cytochrome c peroxidase
active site structure, 162
Compound I, bond length, 167
Cytochrome c peroxidase
contd.
properties, 154
resting state, 51
Cytochrome oxidase, 152, 165
Cytochrome P450 reductase, 3
alternative electron acceptors, 120
antibodies to, 222
fungal, 602, 605
chemical crosslinking to P450, 129
chromosome location, 119
Class I, 587
Class II, 115,587,589,596
determination of activity, 647'
diversity of, 118
electron flow, 124, 125, 127, 128, 131, 133
flavin orientations, 96, 97
fusion proteins with, 115, 116, 133, 587,
601,
603
gene organization, 118, 119, 599
hydride transfer, 122, 124, 125, 126, 127
inhibition, 123,127,266
interaction
with cytochrome b5, 133, 134, 606
with cytochrome c, 116, 129, 130
withP450,95, 116, 128,129, 130
ionic strength effects, 130
kinetic scheme, 126, 127
knockout, 119, 120,605
membrane binding domain, 117, 118, 119, 129
mobility, interdomain, 128-130
mutagenesis, 124, 128
NADPH/NADP+ binding, 122, 123, 126-128
isotope effect, 124, 125
in CYP55 (P450nor), 587
plant, 118, 122,225
photoreduction, 96
properties, 117
ratio to P450, 129
redox properties, 117, 124, 125, 128, 132, 133
regulation/induction, 119, 362, 365
structure of, 95, 97, 117, 121, 122, 123, 127
domains, 117, 118, 122, 124, 125, 129, 131
truncated forms, 117
Cytokines, 388
Dahl Salt Sensitive rat, 543
Daidzein, 554, 571
Dapsone, 407, 409, 426
Daunorubicin, 599
DDEP, see 3,5-Z?w(Carbethoxy)-2,6-
dimethyl-4-ethyl-1,4-dihydropyridine
DDMS,
293
DDT, 330, 332
5-Deazariboflavin,
96, 127
Debrisoquine, 378, 383, 386, 621, 626, 636
polymorphism, 386, 387, 414, 418
Decalin, 31
Index
671
Decalol, 31
Deforaiylation, 6
Dehydration reaction, by P450, 562
Dehydroepiandrosterone hydroxylation, 379,433
Dehydrogenation, see Desaturation
5a-Dehydrotestosterone, 544
Deinococcus radiodumns, 589
Delaviridine, 280, 283, 284
11-Deoxycorticosterone, 447, 453
1
l-Deoxycortisol, 453
11-hydroxylation, 379, 446
6-Deoxyerythronolide
B, 90, 103, 163
Deprenyl,258,259,415
Desaturation, 210
acetaminophen, 211
cytochrome b5 electron donor, 133
dihydropyridine, 211
isotope effects, 209, 210
hydrocarbon, 134, 208-211
lovastatin, 425
mechanism, 209
3-methylindole, 211,422, 436
sterol, 210, 586, 592, 601-604, 608
substrates for, 208
see Valproic acid
Desferoxamine, 258
Desulfuration, 251
Detergent, non-ionic, metabolism of, 425
Dexamethasone
in decrease of
CYP2C11,
363
as inducer, 324, 325, 326, 386, 408,412, 424,434,
438,621
Dextromethorphan, 265, 426, 621, 627
cooperativity in metabolism of, 429
Developmental effects, 388, 432
DHEA,441,449
16-hydroxy, 452
-3-sulfate, 622, 630
Dhurrin, 557, 561, 562-564, 573
Diabetes effects on
drug metabolism, 365,422
fatty acid oxidation, 531
P450 expression, 362, 363, 364, 419, 537
manganese porphyrin effect on, 24
Diallylsulfide, 254, 268
Diallylsulfone, 254, 268, 636
Dibenzo[<3,/]pyrene, 401
ll,12-diol,401
2,3-Diazabicyclo[2.2.0]hex-5-ene, 277
Diazenes, 275
Diazepam, 426
12,12-Dibromododec-ll-enoic acid, 293
2,3-Diazabicyclo[2.2.0]hex-5-ene, 275
Diazinon, 413
Dibenz[a,h]anthracene, 363
1,2-Dibromoethylene,
420
^m(2,3-Dibromopropyl)phosphate, 384
2,2-Dichloroacetamides
N-monosubstituted, 250, 263
2-(/7-bromophenethyl)-, 255
2-(p-nitrophenethyl)-, 255
A^-(l,2-diphenethyl)-,255
2,6-Dichlorobenzonitrile, 405
1,1-Dichloroethylene,
200, 420, 636
1,1-Dichloroethylene
epoxide, 200
1,2-Dichloropropane,
420
N-(3,5-Dichloro-4-pyridyl)-4-methoxy-3-(prop-2-
ynyloxy)benzamide, 272
3-[2,3-Dichloro-4-(2-thenoyl)phenoxy]propan-1
-ol,
621,626
1,4-^/5[2-(3,5-Dichloropyridyloxy)]benzene,
329
3-[2,3-Dichloro-4-(2-thenoyl)phenoxy]propan-l-ol, 411
Diclofenac, 100, 102, 105, 107, 283, 284, 394,
409^11,621,626,635
cooperativity in metabolism of, 428, 429
Dictyostelium discoideum, 591, 610
Dieldrin, 189
Diet, effects on P450, 364, 365, 430, 536, 537, 541, 543
Diethyldithiocarbamate, 250, 404, 421, 621, 627
Diethylnitrosamine, 277, 384
2,2-Diethyl-4-pentenamide, 268
l,2-Difluoro-4-iodobenzene, 17
Dihydralazine, 275
24,25-Dihydrolanosterol, 462
Dihydroquinolines, 2,2-dialkyl, 273
6' ,7'-Dihydroxybergamotin, 250, 261
1,25-Dihydroxycholecalciferol,
451
7a,27-Dihydroxy-4-cholesten-3-one, 457
7a,12a-Dihydroxy-4-cholesten-3-one, 457
3p,7a-Dihydroxy-5-cholestenoic acid, 457
7a,27-Dihydroxycholesterol, 457
la,25-Dihydroxyvitamin
D3,
425, 454, 455
24,25-Dihydroxyvitamin D3,460
Diltiazam, 622, 629
1,1 -Dimethylallene, 283
N,N-Dimethylaniline, see Aniline
7,12-Dimethylbenz[a]anthracene, 363, 395, 401
3,4-diol,401
N,N-Dimethylbenzamide, 195
4,4-Dimethylbiphenyl, 64
Dimethylnitrosamine, 384, 420
cis-3,4-Dimethyl-2-(3-pyridyl)thiazoHdin-4-one, 403
Dimethyl sulfide, 76
1,7-Dimethylxanthine,
403
1,8-Dinitropyrene,
401
Diol, cleavage of, 211, 212
Dioxin response elements, 337, 338
Dioxygenase reductase, 588
Dioxiranes, 222, 223
Disease links to mutations, 383
Disulfiram,386,404,421
Dityrosine, 601-603
672
Index
l,2-Dithiole-3-thione, 254
Diuron, 566
DMZ, 101, 102, 106, 107
DNA binding domain, 323
DNA microarrays, 334
Docetaxel, 431
11-Dodecenoic acid, 211
10-Dodecynoic acid, 294
11-Dodecynoic acid, 250, 293
Doxorubicin, 120
DR-1,440
Drosophila, 553
Drug interactions, 389, 394, 430
DTT, 104
Dwarfism, in plants, 556, 558, 560
Ebastine, 437
Eburicol, 604
Econazole, 593
EDHF,
540, 542
EETs
formation by P450, 292, 423, 533, 539, 541, 545
in glycerophospholipids, 541, 542
metabolism of, 553
physiological properties, 293, 541
role in membrane biology, 293
5,6-EET,
533, 535, 539, 542, 543
8,9-EET,
533, 535, 539
11,12-EET, 535, 538, 539, 540, 542
14,15-EET,533,545,539
EGF signaling, 541
Eicosanoids, 531-534, 543
metabolism of, 380, 533, 535
Electric field, protein, 51
Electron correlation, 47
Electron density, 191
unpaired, 186, 204
Electron transfer, 115, 124
conformational gating, 128
partners, classes of, 115
pathway, 96, 127
toP450, 183, 124-128, 131-133
from radical to iron, 192
see SET mechanism
Electrostatic terms, 51
Ellipticine, 398, 641
Embryogenesis, 119
Endocrine regulation, 347, 348
Endoplastic reticulum proliferation, 328
Endotoxin, 440
ENDOR, 17, 161, 165, 185, 191, 192
Enhancer elements, 324, 328, 336, 405
Enthalpies of formation, 47
Epidermin, 565
Epidermophyton spp., 603
Epiheterodendrin, 564, 565
Epipodophyllotoxin, 431
Epitope mapping, 93
Epothilone, 99, 103,595
Epoxidation
charge transfer, 269
electronic effects, 73, 185, 203
see Heme adducts
mechanism, 6, 73, 198, 269
see Metalloporphyrin
olefins, 185
orbital diagram of ferryl, 67, 73, 74
see Acetylenes, oxidation of
see Aromatic rings, oxidation of
stereochemistry, 19, 198
versus hydroxylation, 79
4p,5p-Epoxyandrostenedione, 290
Epoxide hydrolase, 392, 539
24(5)-Epoxycholesterol, 440
EPR, 17, 21, 33, 54, 156-160, 165, 167, 185, 191,
194,207
Ergosterol biosynthesis, 120, 210, 586, 592,
602-605,
610
Erythromycin
biosynthesis, 163, 598-600
breath test, 426
as inhibitor, 265, 394, 430
as substrate, 386, 425, 426, 428, 621, 628, 637
Equilenin, 205
ERK1,455
ERK2,
455
ERK5,
455
Esterase, 392
Estradiol
biosynthesis, 450, 452
metaboHsm, 204, 378, 380, 384, 399, 400,
401,
633
enhancement by aNF, 427
in P450 regulation, 363, 364
Estriol, 452
Estrogen
biosynthesis, 218
-dependent tumors, 401, 402
in P450 regulation, 351, 440
Estrone, 204, 399,
401,
450, 452
Ethane, 69, 71,267
Ethanol
asinducer, 364, 386, 621
as substrate, 418, 419, 421
tolerance of microbes, 586
4-Ethinylbiphenyl, 271
7-Ethoxycoumarin, 258, 260, 260, 406,422, 621, 639
isotope effect on oxidation, 194
7-Ethoxyresorufin, 397, 400, 621, 624
7-Ethoxy-4-(trifluoromethyl)coumarin, 258, 621, 639
Ethyl carbamate
activation of, 384, 420
desaturation of, 211
Index 673
Ethyl methanesulphonate, 556
Ethylbenzene oxidation, 9, 163
stereochemistry, 9, 25
Ethylene
from diethylnitrosamine, 277
computational studies of oxidation, 6, 73, 74, 77, 201
heme N-alkylation, 74, 199, 255, 267, 268
Ethylene glycol, in radiolysis, 158
2-Ethylhexanoic acid, 209
2-(Ethylhexyl) phthalate, 332
Ethylmorphine, 347, 348, 639, 646
19-(Ethyldithio)androst-4-ene-3,17-dione, 289
7-Ethynylcoumarin, 250, 258, 259
17a-Ethynylestradiol, 250, 256, 258, 259, 394, 406,
423,430,431
1-Ethynylnaphthalene,
250
2-Ethynylnaphthalene, 250, 257, 258, 263, 271
2-Ethynylphenanthrene, 271
3-Ethynylphenanthrene, 271
9-Ethynylphenanthrene, 271, 625, 634
np-Ethynylprogesterone, 250, 256, 257
18-Ethynylprogesterone, 447
1-Ethynylpyrene,
250, 256, 257, 270, 271, 285
2-Ethynylpyrene, 402
Evolutionary relationships, 541, 555, 567, 596
EXAFS,
17
Exemestane, 288, 289, 452
Expressed sequence tag (EST), 554, 557, 567, 575
Ezlopitant, 209, 427
FAD,
115, 116, 118
affinity for, 122
domain, 121, 127
reduction of, 124, 126, 133
Fadrozole, 287
Farnesoid X receptor (FXR), 440, 443
Fasting, 331, 334, 537
Fatty acid, 131
o) and
(0-1
hydroxylation, 213, 292, 378, 420, 434,
435,
532, 535-537, 539, 545, 555, 621, 631
w-2,
(0-3 hydroxylation, 621, 631, 595, 596
metabolism, 330, 331, 380, 603
P-oxidation, 539
Felbamate, 429
Feminization, 446
Fer, 135
Ferredoxin, 115, 135
fusion protein with, 588, 592, 594
Ferredoxin reductase, 115, 118, 135
Ferric peroxo anion, 5, 6, 150, 155, 183, 185, 215, 217,
219,220,222
computational studies, 54, 55
reaction with nitrile, 425
Ferric hydroperoxo
as oxygen donor, 5, 6, 19, 66, 77, 152, 185, 186,
190-192
Ferric hydroperoxo
contd.
bond length, 57
in amine oxidation, 197
in olefin epoxidation, 201
dissociation, in peroxidases, 154, 160
EPR parameters, 159
as P450 intermediate, 3, 5, 48, 56, 151, 153, 156,
157,
183
pH dependence of
role,
217
pKa, 57, 59
protonation, 54, 56, 58, 63, 155, 158, 164
spectrum of, 160
spin state, 155
stability of, 157
structure, 57
Ferric hydrogen peroxide complex, 51
Ferricyanide, 274
Ferrocene, 102, 108
Ferrous dioxygen complex
computational studies, 54-57, 168
pKa, 56
as P450 intermediate, 3, 48, 150, 151, 153, 183
protonation of, 56, 57, 63, 155, 156, 161
radiolysis of, 166
resonance Raman of, 156
spectrum of, 160
stabilization of, 55, 167
structure of, 167
Ferryl species, 6, 48, 59, 183
and active site polarity, 79
calculations on, 51, 66, 77, 78
chameleon species,
60-63,
79
electronic state, 59-62, 66, 67, 72, 74, 77
formation of, 3, 58, 155, 156, 161
electrophilicity of, 77
ligand dependence of properties, 59
role in substrate oxidation, 8, 11, 150, 151, 153, 186,
192
structure, 167
see also Compound I
Ferulic acid hydroxylation, 555
a J-Fetoprotein transcription factor (FTF), 443
Fexofenadine, 394
Filipin biosynthesis, 601
Finasteride, 425
FK506,281,598
Flash photolysis, 127, 136
Flavin-containing monooxygenase, 6, 253
Flavin hydroperoxide, 6
Flavanone, desaturation of, 211
Flavodoxin, 118, 120, 121, 132, 138,213
as redox partner to P450cin, 588
as fusion domain on P450, 588
Flavodoxin reductase, 588
Flavonoid
biosynthesis, 570
674
Index
Flavonoid
contd.
3'-hydroxylase, 555
6-hydroxylase, 569
Flavones, 394
Fluconazole, 250, 290-293, 386, 432, 604, 605
resistance to, 606, 608, 609
structure of, 607
Fluometuron, 566
Fluorescence
emission, 126
quenching, 428
Fluorescent reporter group, 103
Fluoranthene-2,3-diol, 401
15a-Fluorolanost-7-en-3p-ol, 291
20-Fluoro-17(20)-pregnenolone, 292
5-Fluorouracil,
363
Flurbiprofen, 409
Fluroxene, 268
Fluvoxamine, 386, 399, 642
FMN, 115, 116, 118, 132
affinity for, 121
binding domain, 120, 121, 129
reduction of, 124
Formic acid, as product, 282, 283
Formononetin, 571
Forskolin, 459
FprA, 125, 127, 135
Furafylline, 279, 285, 386, 399, 400, 621, 624, 633
Furan oxidation, 261, 262, 280
Furanocoumarins, 250, 261, 430, 553
Fusarium oxysporum, 115, 169, 603
Fusion proteins, 115, 116, 133, 435, 587, 588, 592, 594,
601,603
see P450BM-3
Galangin,621,624, 633
Gender effects, see Sex-linked differences
Gene duplication, 414
Gene knockout mice, see Null mice
Gene organization, 555, 567
Gene therapy, 454
Genistein, 454, 554, 571
Genomes
bacterial, P450 enzymes in, 589, 599
human, P450 enzymes in, 347, 378
Geosmin, 598, 601
Geraniol, 569
Gestodene, 250, 253, 270, 285, 386, 430, 432, 621, 628
GH, See Growth hormone
Giardia lamblia, 590
Gibberellafujikuroi, 226, 229, 603
Gibberellin biosynthesis, 225, 228, 229, 603
Glaucoma, P450 link, 383, 396, 400, 401
Glucocorticoid, 324
receptor, 326, 446
(3-Glucosidase, 560
Glucosinolates, 553-555, 557, 564, 565, 574
Glutathione, 24, 539
Glutathione reductase, 98
Glutathione transferase, 539
Glycerol, effects of, 128, 158, 159
Glycine max (soybean), 566, 569, 571
/'-Glycoprotein, 394, 424, 426
Glycyrrhiza echinata (licorice), 571
Gonadal hormones, 350, 366
Grapefruit juice, 261, 262, 394,430
Green fluorescent protein, 563
"Green pigment", 267, 277, 278
GRIP-1,330
Griseofulvin, 278, 279, 402
Grotthuss mechanism, 56, 162
Growth hormone
age-dependence, 350
in regulation of
P450,
350, 351, 354, 359,
363,
459
receptor, 355-357, 362
secretory pattern, 351-353, 355-360
alteration by xenobiotics, 363, 364
GSTYa, 338
Gynecomastia, P450 link, 383
Halobacterium NRCl, 589
Halocarbons, 263, 283, 285
Halothane, 285, 403, 420, 422
Hammett relationship, 28, 185, 195, 197
HAT mechanism, 196, 197, 204, 211, 228
HDL, 541
Heart disease, 287
Heat shock protein. See Hsp90
Helianthus tuberus (artichoke), 555, 557
Helicoverpa zea (corn), 553
Helminthosporium turcicum, 568
Hematinic acid, 282
Heme
adducts of, 260, 267, 272, 273, 281, 283
meso-a\ky\-, 222
N-alkyl/arylation of
mechanism, 74, 75, 199, 201, 256, 257, 276
myoglobin, 274
regiochemistry, 268, 270, 274, 278
reversibility, 269
stereochemistry, 268
bleaching, 282
carbene complexes, 264, 265, 285
covalent binding to protein, 435, 436
of fragments, 280, 281, 430
iron-alkyl/aryl complexes, 273, 274, 275, 285
irradiation to disrupt complexes, 264
nitroso complexes of, 266
quantitation of, 645
reduction potential, 89
Heme degradation, 155, 251
Index
675
Heme oxygenase, 120, 150, 151, 153
hydroperoxo complex, 159
Hemoglobin, 156, 195,281
hydroperoxo complex, 158, 159
iron-aryl complex, 274
Hepatic toxicity, 253, 275
Heptamylose sugars, 25
Hepatocyte nuclear factors, See HNF
Hepatitis A, P450 decrease due to, 404
Hepoxilins, 531
Herbicides, 553, 556, 566, 595, 598, 599
HET0016,293,622,630
HETEs
formation by lipoxygenases, 531
formation by P450, 292, 536
metabolism by P450, 294, 553, 535
physiological roles, 293, 294
5-HETE,
535
9-HETE,
535
12-HETE, 535, 536
15-HETE, 535
16-HETE, 535
17-HETE, 535
18-HETE, 535
19-HETE, 535, 538
20-HETE, 535, 538, 543-545
vasoconstrictor, 538, 542, 543
Hexane,
1-hydroperoxy,
5
3,4,5,3',4',5'-Hexachlorobiphenyl, 363
15-Hexadecynoic acid, 294
Hexahydro-l,3,5-trinitro-l,3,5-triazine, 588
Hexamethylphosphoramide, 403,405
3-Hexene, 267
Hexobarbital, 347, 348, 408, 412, 646
3-Hexyne, 283
HIFla and related, 338
Histone deacetylase, 324
HIV protease inhibitors, 430
HNF,
387,
398,
443
HNFla,361,419,433
HNF3P,361,433
HNF4a, 326, 330,
361,
402, 408, 413, 425, 433, 440,
443
HNF6,
361
Homology models, see Sequence, structure models
Hordeum vulgare (barley), 555, 561, 564, 566
Hormone
deficiencies, sex hormones, 383
gonadal, 350, 366
see Growth Hormone
luteninizing, 363
parathyroid, 454, 459, 538
phytohormones, 554, 556, 558, 569, 574
replacement therapy, 450
status,
347
see Thyroid hormone
Horseradish peroxidase
axial ligand, 51
catalytic residues, 154
Compound I, 195
iron-oxygen bond length, 167
rate constants for formation, 154
Compound III, 156
computational studies, 62
ferric hydroperoxo complex, 158, 159
substrate peroxidation, 207
substrate peroxygenation, 196, 198
Host-guest complex, 25
15-HEPTE, P450 role, 532, 533
Hsp90, 336, 337, 397
Humoral hypercalcemia, 459
Hydrazines, 274
acyl-, 263
l,l-dialkyl-,263,275
heme destruction by, 273, 275, 281
hemoprotein complexes of, 266, 267, 274
radical formation from, 273
Hydrocortisone, production of, 586, 587
Hydrogen bonds, low energy, 57
Hydrogen peroxide, 281
Hydroperoxide, see Oxygen donors
Hydroperoxide lyase, 555
20-Hydroperoxycholesterol, 286
10-Hydroperoxy-4-estren-3,17-dione, 290
Hydrostatic pressure, 165, 429
N-Hydroxy-2-acetylaminofluorene, 3 84
4-Hydroxyandrost-4-ene-3,l7-dione, 289, 290
;7-Hydroxybenzaldehyde, 561
N-Hydroxy-N' -(4-butyl-2-methylphenyl)formamidine,
293
5-exo-Hydroxycamphor,
167, 595
dehydrogenase, 595
7a-Hydroxycholesterol, 457
20-Hydroxycholesterol, 440
24-Hydroxycholesterol, 440
7-hydroxylation,
379, 440, 460
25-Hydroxycholesterol, 440, 441
27-Hydroxycholesterol, 440, 459
6p-Hydroxycortisol, 426, 621
8-Hydroxyeicosatetraenoic
acid, 436
12-Hydroxyeicosatetraenoic acid, 436
12-Hydroxyheptatrienoic acid, 439
12-Hydroxy-8,10-heptadecadienoic acid, 439
12-Hydroxy-5,8,10-heptadecatrienoic acid, 547
12-Hydroxy-5,8,10,14-heptadecatetraenoic acid, 439
Hydroxylamines, 266
11
P-Hydroxylase, see CYPl IB
17a-Hydroxylase/C 17,20 lyase, see CYP17A
Hydroxylation
alkane, 7, 186
allylic, 4, 9, 68, 70, 72, 73, 185, 535, 536
barrier height, 12, 47, 70, 71, 72, 161
676
Index
Hydroxylation
contd.
benzylic, isotope effects, 196
bond strength, 30, 66, 196
hydrogen abstraction, 189, 193, 212
see Isotope effects, hydroxylation
mechanism, 186, 191
prediction of
site
reactivity, 66, 421, 427
radical intermediate in, 12, 13, 66, 193, 212
rearrangements, 9, 68, 186
rebound mechanism, 192, 193
stereochemistry, 4, 5, 9, 186, 193
transition state, 4, 9, 11, 67, 69, 71
tunneling effects, 14
versus epoxidation, 79
Hydroxyl radical
formation, 155
quenching, 159
/7-Hydroxymandelonitrile, 561, 562, 563
a-Hydroxynitrilase, 560
^ra«5-4-Hydroxy-2-nonenal, 283
4-Hydroxyphenylacetaldoxime, 555, 557, 561, 562
/7-Hydroxyphenylacetonitrile, 561
7a-Hydroxyprogesterone 12-hydroxylation, 379
17-Hydroxyprogesterone 21-hydroxylation, 379,453
12-Hydroxystearic acid, 436
la-Hydroxyvitamin
D3,
458
2
5-Hydroxyvitamin
D3
la-hydroxylation, 460
24-hydroxylation, 379
hydroxylation pathways, 455
Hyperaldosteronism, 447
Hypercholesterolemia, P450 link, 383
Hypercortisolism, 249
Hyperglycemia, 363
Hyperketonemia, 363
Hyperlipidemia, 363
Hyperoxysterolemia, P450 link, 383
Hypersensitivity, idiosyncratic, 262, 410, 422, 443
Hypertension, 253, 383, 447, 531, 532, 537, 542
Hypervitaminosis D, 455
Hypoglycemia, 334
Hypophysectomy, 351, 353, 355, 357, 362
Hypothalamic-pituitary axis, 351, 363
Hypothyroidism, 362
Hypoxia inducible factors, 120, 338
Ibuprofen, 410
Imidazole
binding of, 435
in P450 inhibition, 249, 593, 605
structure of P450 complex, 100
10-Imidazolyldecanoic acid, 622, 630
Imipramine, 365
Indigo, 403, 420
Indole, 403, 420, 567, 568
Indole-3-acetaldoxime, 555
Indole-3-glycerol phosphate, 567, 568, 574
Indolin-2-one, 567
3-hydroxy-,
567
Indomethacin, 227, 285
Induction ofP450, 324, 621
barbiturates, 386, 393, 394, 407, 424, 431
charred food, 387, 399, 621
clofibrate,331,332,354,402
cruciferous vegetables, 399, 621
DDT, 387
dexamethasone, 324, 386, 408, 424
diphenylhydantoin, 387, 396
ethanol, 364, 365, 386, 387
exercise, 399
isoniazid,386,418,419, 621
mechanism of, generalized, 388
PCN, 324
phenobarbital, 402, 408, 412, 621
pharmacokinetic effects, 393, 394
polychlorinated biphenyls, 387, 397
poly cyclic aromatic hydrocarbons, 419
via protein stabilization, 266, 399, 419, 425
pyrazole, 402
see Regulation
rifampicin, 325, 386, 387, 394, 402, 407, 408, 412,
424,431,433,434
via RNA increased translation, 419
via RNA stabilization, 419
smoking,386, 397, 399, 621
St. John's wort, 430, 431
troleandomycin, 621, 637
TCDD, 335, 397, 538
Inflammation, 24
P450 link to, 383, 402
Inhibition, 389
acetylenes, 199,399
AIA,
255,
267,
268,
641
aldehydes, 222
1-aminobenzotriazole,
275, 276, 294, 641
by antibodies, 390-392
diagnostic, 621
mechanism-based, 247, 394, 430, 447, 450, 452
allosteric stimulation of, 428
heme modification by, 250, 256, 257, 260, 263,
267,
284
protein modification by, 250, 252, 253, 254, 256,
259,
262,
263,
267,
271,
404, 406, 410
carbon monoxide, 248, 641
computational studies of binding, 64
cyclopropylamines, 196
dihydropyridines, 272, 641
glutathione as test of
type,
251, 252, 258, 259, 261,
262,275,
280
hydrazines, 267
iron coordination, 247, 274, 543
isoform selectivity, 251, 252, 255, 261, 271, 275
Index
677
Inhibition
contd.
metabolic intermediate (MI) complex, 262, 263, 264,
265, 425,
645
olefins, 199
quasi-irreversible, 247, 250, 265
partition ratio, 199, 252, 253, 257, 260, 267, 270, 279
substrate competition, 247
surfactants, 285
sydnones, 277, 278
types,
247
Insect attractants, 554
Insects, 590, 592
Insecticide resistance, 553
Insulin, 364, 365, 440, 537
Interferon-7 response element, 442
Interleukins, 419, 425, 440,451
lodosobenzene, see Oxygen donors
Ion channel regulation, 542
Ifosphamide, 362, 363, 365
Indinavir, 425
4-Ipomeanol, 422, 436
Irbesartan, 411
Iron-sulfiir protein, 115, 116
Isoandrocymbine, 205
Isocyanate, a-keto-, 253
Isocyanide complexes, 169, 644
Isoflavone synthase, 227, 228
Isoflavonoids, 553-555, 569, 570
Isoflurane, 420
L-Isoleucine, glucoside precursor, 561, 564, 565
Isoniazid, 266, 386, 404, 418, 419
Isonitriles, as product, 285
Isoporphyrin, 222
2-isopropenyl-2-methyladamantane, 406, 621, 625
3-Isopropenyl-3-methyldiadamantane, 406, 621, 625
2-lsopropyl-4-pentenamide, 255, 267, 641
i^O-studies, 268
Isosafrole, 264, 282, 399
Isothermal titration calorimetry, 98, 135
Isothiocyanate, 250
benzyl-, 254
^butyl-, 254
phenyl-, 254
Isotope effects
ir-bond oxidation, 207, 270
on carcinogenicity of nitrosoamines, 421
in heteroatom dealkylation, 194, 265, 399, 417
in elimination reaction, 223, 272, 283
effect of reorientation in site, 64
on enzyme inactivation, 279, 283
on hydroxylation, 186, 193,427
acetaldehyde, 421
alkyl,4,8,30,68, 164, 189
allylic, 4, 9
benzylic, 64
ethanol, 421
Isotope effects
contd.
intrinsic, 188
inverse, 198, 202, 203
masking of, 64
in oxidation of
acetylenes,
270
in oxygen activation, 417
solvent, 56, 128, 164, 165
Isovaleric acid decarboxylation, 226
Issatchenkia orientalis, 591
Itraconazole, 593, 605
resistance to, 608, 609
structure of, 607
Jak2,
tyrosine kinase, 357-359
Jasmonate, 553, 569
Kaempferol, 408
ent-Kaurene oxidase, 555
e«^Kaurenoic acid, 225, 555
Kavapyrones, 430
Ketamine, 406
Ketene, 257, 258
Ketoconazole, 120, 249, 253, 290, 291, 386, 394, 430,
432,
433, 593,
604,
621,
642,
450
resistance to, 605, 606, 609
structure of, 607, 628, 642
suppression of P450 expression, 424
Ketoprofen, 227
L-754,394, 250, 262
Langmuir-Blodget, 95
Lanosterol, 1, 219, 461, 592, 605
Lanosterol 14-demethylase, see CYP51
Laser flash photolysis, 9, 96
Laurie acid oxidation
desaturation, 211
reconstitution of activity, 117
as substrate, 132, 283, 378, 380, 420, 434-436, 533,
537,
538,
622, 630, 637
LDL, 541
Leischmeinia, 610
Lens culinaris (lentil), 571
Letrozole, 287, 288
Leucoanthocyanidins, 570
Leukotriene B4 hydroxylation, 378, 436, 437, 534, 535,
621,631
Leukotrienes
in physiology, 332
metaboUsm, 294, 352, 378
L-Leucine, glucoside precursor, 561, 564
Lidocaine, 365, 426, 636
Ligand, axial
ammonia, 54
calculations on, 51, 52, 59, 61
catalase, 51
see Cysteine ligand