Cytochrome P450
3A7
Oxygen
Cytochrome P450
26
CYP2R1
pyrophosphate
Cytochrome P450
2W1
H2O
4-cholesten-7alpha,
12alpha,27-triol-3-
one
H+
alcohol
dehydrogenase
complex
H+
Cholesterol
NADP+
Acetaldehyde
NADP+
NADPH
4-Aminobiphenyl
Oxygen
Formate
TBXAS1
Oxindole
Phenylacetaldehyde
Oxygen
H+
H2O
24-
hydroxycholesterol
Oxygen
H2O
NADPH
H+
Oxygen
H+
H+
H2O
4-hydroxyestradiol-
17beta
4,4-
dimethylcholesta-8
(9),14,24-trien-
3beta-ol
H2O
NADP+
Cytochrome P450
4F2
CYP2D6
Progesterone
Phenol
Cytochrome P450
4F8
Oxygen
NADPH
Leukotriene B4
Spermine
Formaldehyde
H+
H2O
H+
NADPH
9-cis-retinoic acid
Arachidonate
Oxygen
Methimazole
Oxygen
H2O2
NADPH
NADPH
Indole
H+
NADPH
NADPH
Debrisoquine
NADP+
Arachidonate
H2O
Coumarin
Prostaglandin H2
Testosterone
N-acetylspermidine
Spermidine Oxidase
(SMOX)
CoA-SH
NADPH
NADP+
5-Hydroxytryptamine
Trimethylamine
Cytochrome P450
26C1
CYP3A43
H2O
NADP+
3-acetamidopropanal
NADP+
Hydrogen
Oxygen
NADPH
Oxygen
4-hydroxyphenytoin
NADPH
3-acetamidopropanal
Vitamin D3
NADP+
H2O
H+
1,24,25-
trihydroxyvitamin D3
H2O
Cytochrome P450
2C19
Oxygen
24-
hydroxycholesterol
N-acetylspermine
Dextromethorphan
H2O
Trichloromethyl
radical
NADP+
NADPH
Cytochrome p450
46A1
H2O
Estradiol-17beta
NADP+
19-
hydroxyprostaglandin
H2
3-methylindole
H+
CYP11B1
NADPH
4-Androstene-3, 17-
dione
Oxygen
H+
NADP+
3-hydroxypalmitate
NADP+
Tamoxifen N-oxide
H+
ChEBI
37623
Uniprot
P05108
NADP+
NADH
ChEBI
16827
ChEBI
16521
2-Phenylethylamine
ChEBI
42977
Cytochrome P450
7B1
ChEBI
16973
NADPH
ChEBI
17026
Reactome
REACT_10253
ChEBI
1294
ChEBI
17650
Oxygen
Aflatoxin exo-8,9-
oxide
H2O
Uniprot
P05093
3-methyleneindolenine
Estrone
NADP+
4-hydroxy-all-trans-
retinoic acid
H2O
Oxygen
ChEBI
15377
Oxygen
Uniprot
P98187
Cytochrome P450
3A4
Uniprot
P24557
H2O
ChEBI
10545
H2O
H+
CYP21A2
6-hydroxypaclitaxel
19-hydroxyarachidonic
acid
NADP+
NADPH
Spermidine
ChEBI
15554
Pregnenolone
H+
Uniprot
Q08477
Uniprot
Q16647
ChEBI
17263
ChEBI
15378
ChEBI
18009
Reactome
REACT_14525
ChEBI
37248
Oxygen
Reactome
REACT_14617
NADP+
Uniprot
Q8TAV3
Uniprot
Q9UNU6
H+
H+
Uniprot
P19099
ChEBI
17703
ChEBI
17998
Uniprot
Q9Y6A2
ChEBI
15552
4-
hydroxycyclophospham
ide
Ethanol
ChEBI
15724
NADPH
Reactome
REACT_14315
NADPH
ChEBI
18139
ChEBI
41774
NADP+
Reactome
REACT_14663
Prostaglandin H2
Acetyl-CoA
H2O2
Uniprot
Q9HBI6
Cytochrome P450
2A6
H2O
Oxygen
Cytochrome P450
4F11
Reactome
REACT_20049
17alpha-
hydroxypregnenolone
ChEBI
27647
ChEBI
16240
ATP
NADPH
ChEBI
16134
Uniprot
P78329
ChEBI
16474
Reactome
REACT_13855
ChEBI
15627
Cholest-5-ene-3beta,
7alpha,24(S)-triol
NH3
Cytochrome P450
2C9
ChEBI
18397
NADP+
NADPH
H2O
ChEBI
28790
ChEBI
50157
Oxygen
ChEBI
15760
Oxygen
ChEBI
15621
NADP+
20-OH-leukotriene B4
NADP+
NADPH
Halothane
ChEBI
30322
Prostacyclin
ChEBI
17312
Oxygen
Reactome
REACT_14616
ChEBI
17927
ChEBI
16424
NAD+
Oxygen
Reactome
REACT_14612
Uniprot
Q16696
Oxygen
Reactome
REACT_14369
CYP17A1
Uniprot
P04798
Reactome
REACT_14339
Cytochrome P450
39A1
ChEBI
15746
H+
ChEBI
17148
NADPH
Ethylene oxide
ChEBI
18090
ChEBI
16027
ChEBI
16610
Oxygen
Cytochrome P450
3A5
ChEBI
4026
Oxygen
Oxygen
NADPH
Uniprot
P10632
Uniprot
P24462
Reactome
REACT_14465
H2O
Reactome
REACT_14215
H2O
H2O
ChEBI
15846
NADPH
ChEBI
15422
6beta-
hydroxytestosterone
Cytochrome P450
2U1-1
ChEBI
16908
ChEBI
15346
ChEBI
15351
H+
NADPH
H2O
25-
hydroxycholesterol
H2O
NADP+
NADPH
Uniprot
P24903
Uniprot
P20815
Uniprot
P33261
ChEBI
18153
Reactome
REACT_21845
Reactome
REACT_14596
ChEBI
29888
Uniprot
Q9NR19
H+
ChEBI
15366
H+
NADPH
Oxygen
Uniprot
Q9NUB1
Cytochrome P450
27
CoA-SH
3,16-
dihydroxypalmitate
Reactome
REACT_14364
Uniprot
P11509
ChEBI
9171
ChEBI
27561
H+
ChEBI
29133
lanosterol
NADPH
ChEBI
28794
Cytochrome P450
1A1
ChEBI
15646
NADP+
ChEBI
4470
Oxygen
NADP+
Trimethyamine N-
oxide
Methimazole S-
oxide
Reactome
REACT_10249
ChEBI
28477
Reactome
REACT_10645
Cyclophosphamide
ChEBI
17899
N-demethylated
loperaminde
Reactome
REACT_10863
Cytochrome P450
4A11
H2O
Uniprot
O75881
ChEBI
28750
PTGS dimers
CYP51A1
ChEBI
30751
NADPH
H+
Cytochrome P450
2F1
4-cholesten-7alpha,
12alpha,24(S)-triol-3-
one
Uniprot
Q16678
Uniprot
Q02318
H+
H2O
Cytochrome P450
2B6
NADPH
NADP+
Reactome
REACT_10821
ChEBI
15843
ATP
Reactome
REACT_14302
H+
Uniprot
P51589
H2O
ChEBI
30805
PTGIS
Tamoxifen
Uniprot
P11511
Carbon tetrachloride
Uniprot
Q9NYL5
ChEBI
16422
Uniprot
P08686
Vinyl chloride
ChEBI
28324
Reactome
REACT_14354
cis-EET
Uniprot
Q02928
ChEBI
39567
Cytochrome P450
2J2
Reactome
REACT_14303
Uniprot
P13584
ChEBI
16581
ChEBI
34310
H2O
Uniprot
Q16850
Oxygen
ChEBI
16113
Uniprot
P15538
Reactome
REACT_14607
Oxygen
NADP+
ChEBI
17347
NAD+
6beta-
hydroxytestosterone
Uniprot
Q9HCS2
Ethylene
Uniprot
P33260
Reactome
REACT_13974
Reactome
REACT_14175
Thromboxane A2
ChEBI
16469
Acetaldehyde
Oxygen
NADPH
H+
Cytochrome P450
2C8
ChEBI
37640
Tyramine
ChEBI
17500
Uniprot
P22680
Pregnenolone
Oxygen
H+
Cholest-5-ene-
3beta,7alpha,25-
triol
H+
H+
H2O
Cytochrome P450
1B1
H+
NADP+
H+
Homo sapiens
Acetaminophen (TN
TYLENOL)
Phase 1 of metabolism is concerned with <i><b>functionalization</b></i>, that is the introduction or exposure of functional groups on the chemical structure of a compound. This provides a 'handle' for phase 2 conjugating species with which to react with. Many xenobiotics are lipophilic and almost chemically inert (e.g. PAHs) so would not necessarily undergo a phase 2 reaction. Making them more chemically reactive would facilitate their excretion but also increases their chance of reacting with cellular macromolecules (e.g. proteins, DNA). There is a fine balance between producing a more reactive metabolite and conjugation reactions.<br>There are two groups of enzymes in phase 1 - oxidoreductases and hydrolases. Oxidoreductases introduce an oxygen atom into or remove electrons from their substrates. The major oxidoreductase enzyme system is called the P450 monooxygenases. Other systems include flavin-containing monooxygenases (FMO), cyclooxygenases (COX) and monoamine oxidases (MAO). Hydrolases hydrolyse esters, amides, epoxides and glucuronides. (WikiPathways-description)
Cellular Process (WikiPathways-category)
Phase 1 - Functionalization of compounds
Reactome
REACT_14313
ChEBI
15379
ChEBI
15647
H2O
H2O
H+
H+
NADP+
NADPH
Oxygen
H+
Cytochrome P450
8B1
H2O
H+
ChEBI
6532
H+
H2O
NADP+
Uniprot
P10635
CYP2S1
Reactome
REACT_14274
ChEBI
2504
Reactome
REACT_13828
NADPH
1,25-dihydroxyvitamin
D3
H2O
H2O2
NADP+
Hydrogen bromide
Oxygen
NADP+
12-hydroxy-
5,8,11,14-
eicosatetraenoic
acid
NADPH
Ethanol
NADP+
Oxygen
Isocaproic aldehyde
Cytochrome P450
7A1
H+
Calcidiol
NADPH
H+
Corticosterone
Oxygen
Cytochrome P450
2E1
NADPH
NADP+
H2O
H2O
11-
deoxycorticosterone
Oxygen
NADPH
Putrescine
NADP+
Acetate
Oxygen
NADPH
Tolbutamide
NADPH
NADH
NADP+
Acetate
Hydroxycoumarin
Oxygen
4-cholesten-7alpha,
24(S)-diol-3-one
Oxygen
CYPIA2
H2O
ACSS1
All-trans-retinoic
acid
H+
H+
Oxygen
Aflatoxin B1
Testosterone
NADPH
Oxygen
H+
11-
deoxycorticosterone
NADPH
NADP+
NADPH
Oxygen
H2O
H2O
Cholesterol
Oxygen
Oxygen
H2O
NADP+
H+
Oxygen
Chloride
5-
Hydroxyindoleacetalde
hyde
NADP+
Oxygen
NADPH
NADP+
NADPH
Phenytoin
NADP+
NADH
NADPH
NADPH
H2O
Oxygen
Calcitriol
NADP+
4-hydroxytolbutamide
Oxygen
H2O
NADP+
AMP
H2O
Prostaglandin G2
H2O
H+
N-Hydroxy-4-
aminobiphenyl
H+
11-deoxycortisol
Acetyl-CoA
electron
Oxygen
omega-
Hydroxydodecanoic
acid
NADPH
4-hydroxy-9-cis-
retinoic acid
Cytochrome P450
4F12
H2O2
4-hydroxydebrisoquine
H2O2
CYP11A1
Dodecylcarboxylate
NADPH
NADP+
NADP+
H2O
CYP19A1
Oxygen
Benzene
NH3
Cytochrome P450
4F3
H2O
Oxygen
Uniprot
P20813
Acetyl-coenzyme A
synthetase,
cytoplasmic
Oxygen
H2O
ChEBI
25858
ChEBI
16842
Reactome
REACT_14384
ChEBI
2505
Oxygen
H+
H+
H2O
Oxygen
H2O2
4-
Hydroxyphenylacetalde
hyde
H2O
ChEBI
27732
Oxygen
ChEBI
16580
H2O
ChEBI
5615
Uniprot
P05177
ChEBI
1784
H2O
Oxygen
H+
H2O
H+
NADP+
Formate
Oxygen
Loperamide
Paclitaxel
Uniprot
P11712
The start coordinate is not yet known (WikiPathways-description)
CYP27B1
Reactome
REACT_14076
NADPH
Uniprot
P08684
ChEBI
45863
ChEBI
27510
H2O
Cortisol
Formaldehyde
Cytochrome P450
4B1
NADPH
H2O
H2O
NADPH
NADP+
H2O
7 alpha-
hydroxycholesterol
Uniprot
P05181
ChEBI
29132
ChEBI
16236
ChEBI
15882
ChEBI
16716
3-aminopropanal
H2O
NADPH
H2O
Spermidine
Reactome
REACT_14412
H2O
Uniprot
Q6VVX0
Reactome
REACT_14555
ChEBI
28940
Reactome
REACT_14066
Oxygen
NAD+
H2O
Acetaldehyde
H+
ChEBI
29138
ChEBI
15343
Cytochrome P450
26B1
ChEBI
27385
Cytochrome P450
2C18
Paraxanthine
ChEBI
46195
H2O
ChEBI
29129
NADP+
Cytochrome P450
2A13
H+
ChEBI
28509
NADP+
ChEBI
47266
H+
Arachidonate
ChEBI
17996
H+
Reactome
REACT_4348
ChEBI
18276
H+
Reactome
REACT_13891
NADP+
ChEBI
31697
NADP+
ChEBI
16881
CYP11B2
Uniprot
Q7Z449-1
Reactome
REACT_14524
H+
NADP+
PubMed
J Biol Chem 275:26458-66
Hannah, VC
Luong, A
Goldstein, JL
2000
10843999
Molecular characterization of human acetyl-CoA synthetase, an enzyme regulated by sterol regulatory element-binding proteins.
Oxygen
AMP
4-cholesten-7alpha,
27-diol-3-one
pyrophosphate
Oxygen
4-cholesten-7alpha-
ol-3-one
27-
hydroxycholesterol
H2O
H2O
CYP24A1
NADP+
5-hydroxyomeprazole
N-
Acetylbenzoquinoneim
ine
Omeprazole
NADP+
2-Chloroethylene
oxide
H+
H2O
NADPH
ChEBI
17823
NH3
Cholesterol
Uniprot
Q07973
Reactome
REACT_13921
NADP+
Uniprot
O15528
Reactome
REACT_14157
Caffeine
4-cholesten-7alpha,
12alpha-diol-3-one
H+
NADP+
NADPH
18-
hydroxyarachidonate
Uniprot
Q6V0L0
Oxygen
ChEBI
15367
Reactome
REACT_14163
Trifluoroacetylchloride
NADPH
Uniprot
Q9NR63
Dextrorphan
Uniprot
O43174
20alpha,22beta
dihydroxycholesterol