NADPH
H2O
CYP2A13
11DCORST
H+
ADH1B
CHOL3b,7a,25TRIOL
H+
H2O
Cu2+
(2Fe-2S)(1+)
H2O
CH2O
2CEO
NADP+
PEA
H+
H2O
AOC3
H+
CYP3A5
Mg2+
5HT
4-ethoxyaniline
20OH-TrXA3
O2
CYP2A13
FMO2
CYP2A13
HPHT
H+
H2O
MIND
CYP2F1
NADPH
TES
O2
O2
CYP2F1
NADPH
CYP11A1
4HPAA
H2O
FAD
CYP2F1
O2
NH3
CHOL
H2O
CYP4F11
N-demethylated
loperamide
O2
H+
MAOA
CYP2S1
12OH-DDCX
H+
CH3COOH
NASPM
ARA
CYP4A22
CYP2E1
PTGIS
HBr
NADPH
H2O
NADPH
HDBQ
H2O
CYP2A7
PPi
LCHA
NADP+
H2O
H+
NADP+
H+
CYP4F12
O2
CORT
NADP+
20OH-LTB4
4CHOL7a,12a,24(S)TONE
NADP+
CYP2A13
27OH-CHOL
CYP2A13
CYP11B2
7
alpha-hydroxycholesterol
NAD+
CYP4F2
ATP
H2O
LPAM
CYP2C8
H+
H+
EtO
O2
NADP+
H2O
CYP2C18
18OH-ARA
H+
NADPH
LTB4
CYP2C19
CYP4A11
O2
O2
AMP
H2O
CYP2C8
H+
19HETE
ADH1A
CYP4A22
HCPM
O2
CYP2D6
NADPH
CYP27B1(?-508)
The start coordinate is not yet known (Reactome)
NADPH
BEG
e-
CDL
H2O
H2O
NADP+
CYP2E1
CYP2C9
CYP2E1
P4
AFB1
FAD
H2O
H+
CXPA
Acetaminophen (TN
TYLENOL)
4HPCP
NADPH
5,6-EET
CoA-SH
ALDH1A1
H+
NADPH
O2
NADPH
H2O2
H+
CYP2J2
CYP7B1
CYP3A7
NADPH
O2
H+
AADAC
CYP2S1
NADP+
CYP2A13
CYP3A7
CYP39A1
acetyl group
CYP4A22
heme b
CYP1B1
NADP+
25OH-CHOL
CPM
NADP+
O2
O2
NADPH
NADP+
CYP4F12
NADP+
14,15-EET
NADPH
17aHPREG
PTCN
EtOH
CYP2D6
FAD
CYP4F22
H+
CYP24A1
NADP+
P22760
Uniprot
O2
Ac-CoA
H+
EST17b
ACSS2
CYP1A2
H2O2
H+
H+
CYP2A6
CYP2B6
LNSOL
CYP4F2
CYP3A43
O2
FMO3
NADPH
CTLA
Q16853
Uniprot
CHEBI:17169
ChEBI
SMOX-3
ALDH1B1
NH3
FDX1
CYP3A5
NADP+
CHEBI:8050
ChEBI
CORST
NADP+
P30837
Uniprot
CHEBI:85505
ChEBI
CHEBI:40574
ChEBI
H+
CHEBI:17650
ChEBI
CHEBI:1294
ChEBI
CHEBI:34310
ChEBI
CHEBI:16581
ChEBI
H2O
H+
O2
CHEBI:17813
ChEBI
NADPH
ALDH3A1
CYP2C9
CHEBI:17026
ChEBI
NADP+
NADPH
CHEBI:28694
ChEBI
Q16850
Uniprot
CHEBI:16469
ChEBI
CHEBI:40538
ChEBI
CYP2A7
CHEBI:62845
ChEBI
O75106
Uniprot
CHEBI:17500
ChEBI
H+
CHEBI:16113
ChEBI
CYP21A2
BZAL
NADPH
Oxindole
PTGS1
NH3
NADP+
CHEBI:17263
ChEBI
4CHOL7aOLONE
CHEBI:16474
ChEBI
NADP+
CHEBI:15378
ChEBI
CYP2S1
CHEBI:18009
ChEBI
H2O
CYP2A6
CYP2D6
NADP+
H+
CYP2W1
O2
NADPH
H2O
CHEBI:15552
ChEBI
CYP11B2
CHEBI:15377
ChEBI
CHEBI:16521
ChEBI
P05093
Uniprot
H2O
CHEBI:42977
ChEBI
H2O
NADP+
CHEBI:37623
ChEBI
H+
P05091
Uniprot
NADPH
CHEBI:15351
ChEBI
CHEBI:15346
ChEBI
CHEBI:16908
ChEBI
CHEBI:30805
ChEBI
O2
CHEBI:34157
ChEBI
CHEBI:34130
ChEBI
NADP+
CHEBI:34490
ChEBI
ADH7
CHEBI:34450
ChEBI
NADP+
O2
CHEBI:16973
ChEBI
4OH-atRA
DSQ
ACSS1
P00352
Uniprot
CYP8B1
CHEBI:16236
ChEBI
NADPH
CYP17A1
H+
CHEBI:29888
ChEBI
P07327
Uniprot
224930
PubMed
Purification and partial characterization of aldehyde dehydrogenase from human erythrocytes.
Inoue K, Nishimukai H, Yamasawa K.
O2
TMA
H+
Q9NR19
Uniprot
NADPH
CH3CHO
H2O
NADP+
NADP+
BZAM
CHEBI:15366
ChEBI
H2O
NAD+
O2
P00326
Uniprot
P00325
Uniprot
P28332
Uniprot
CYP4F3
P08319
Uniprot
CYP4A11
MAOB
CHEBI:15554
ChEBI
CHEBI:10545
ChEBI
CHEBI:29105
ChEBI
P24557
Uniprot
H2O
ADH6
NCOA2
NADP+
O2
O2
H2O
PhOH
CHEBI:15647
ChEBI
CHEBI:4470
ChEBI
CHEBI:29133
ChEBI
CYP2D6
6BHT
CYP2C9
P40394
Uniprot
CYP2C9
Q9NUB1
Uniprot
MTZ-SOX
H2
Ac-CoA
NADPH
S-HMGSH
Ca2+
O75881
Uniprot
CHEBI:26355
ChEBI
P23219
Uniprot
CYP4B1
P01189
Uniprot
NADH
CHEBI:15646
ChEBI
CYP2J2
H2O
CYP4B1
CYP4F2
TMAO
HTOLB
AOC1
CYP2D6
CHOL
O2
CHEBI:27510
ChEBI
CHEBI:63905
ChEBI
O2
CHEBI:8107
ChEBI
H+
CHEBI:63840
ChEBI
CHEBI:6532
ChEBI
P22680
Uniprot
P20813
Uniprot
P05181
Uniprot
P10632
Uniprot
P33261
Uniprot
NADP+
H2O
NABQI
3MEIN
CHEBI:16842
ChEBI
CHEBI:45863
ChEBI
CHEBI:63804
ChEBI
CYP2C18
CHEBI:30725
ChEBI
NADPH
CYP4B1
O2
H2O
CHEBI:25858
ChEBI
NADPH
O2
P11712
Uniprot
P10635
Uniprot
Q96SQ9
Uniprot
P24903
Uniprot
P11509
Uniprot
H2O
H+
NADPH
CYP4F2
CYP2E1
H2O
10843999
PubMed
Molecular characterization of human acetyl-CoA synthetase, an enzyme regulated by sterol regulatory element-binding proteins.
Luong A, Hannah VC, Brown MS, Goldstein JL.
CHEBI:5615
ChEBI
P05177
Uniprot
CHEBI:1784
ChEBI
H2O
NADPH
CHEBI:27732
ChEBI
NH3
P33260
Uniprot
CHEBI:16580
ChEBI
Q9HB55
Uniprot
H2O
P20853
Uniprot
Q16696
Uniprot
CYP2E1
O2
INDOL
O2
Q7Z449
Uniprot
NADH
CYP4F11
H2O
CHEBI:27385
ChEBI
TBXAS1
CHEBI:17996
ChEBI
CHEBI:46195
ChEBI
NADP+
CHEBI:29138
ChEBI
CYP2E1
P13584
Uniprot
NH3
H2O
Q02928
Uniprot
CHEBI:29129
ChEBI
P51589
Uniprot
NADPH
Q8TAV3
Uniprot
CYP2U1
H2O
Q5TCH4
Uniprot
H+
H+
P78329
Uniprot
CHEBI:19138
ChEBI
CHEBI:39567
ChEBI
CYP2C18
CYP2A7
NADP+
CHEBI:63799
ChEBI
H2O2
CYP11A1
CHEBI:63590
ChEBI
NADPH
CHEBI:17347
ChEBI
CYP4F22
Q9Y6A2
Uniprot
COUM
CHEBI:17998
ChEBI
H2O
O2
CHEBI:17703
ChEBI
Q08477
Uniprot
CHEBI:28477
ChEBI
NADP+
Q6NT55
Uniprot
CHEBI:63839
ChEBI
O2
P15538
Uniprot
Q9HBI6
Uniprot
H2O
CHEBI:64043
ChEBI
Zn2+
CHEBI:34477
ChEBI
CHEBI:1864
ChEBI
P04798
Uniprot
CHEBI:27999
ChEBI
4CHOL7a,27DONE
CHEBI:17899
ChEBI
H+
CHEBI:48333
ChEBI
MTZ
CHEBI:63838
ChEBI
CHEBI:15843
ChEBI
CYP2D6
CHEBI:48825
ChEBI
C2H4
NADPH
CHEBI:4026
ChEBI
CHEBI:63859
ChEBI
CYP2C9
CHEBI:63800
ChEBI
PREG
H+
CES2
CHEBI:18153
ChEBI
TYR
CYP4F3
CYP2S1
CHEBI:34665
ChEBI
H2O2
CHEBI:37640
ChEBI
11,12-EET
NADP+
CHEBI:28750
ChEBI
H2O
CYP2R1
Q02318
Uniprot
H2O
NADP+
CHEBI:30751
ChEBI
Q16678
Uniprot
(2Fe-2S)2+
H+
CHEBI:9171
ChEBI
C6H6
NADP+
CYP2A13
CHEBI:27561
ChEBI
O2
CHEBI:28794
ChEBI
O2
CHEBI:7772
ChEBI
CHEBI:2504
ChEBI
CHEBI:16422
ChEBI
NADPH
CH3COO-
P11511
Uniprot
11DCORST
NADPH
P08686
Uniprot
CHEBI:28324
ChEBI
H2O
Q9NYL5
Uniprot
CYP4A11
FMO1
CYP2A6
CYP2E1
LTB4
CYP8B1
NADPH
CYP2A7
H2O
O2
CYP2C8
NADPH
CYP4B1
H2O
COCN
TES
Homo sapiens
O2
Phase 1 - Functionalization of compounds
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.
View original pathway at:[http://www.reactome.org/PathwayBrowser/#DIAGRAM=211945 Reactome]. (WikiPathways-description)
H+
CHEBI:63912
ChEBI
CHEBI:15379
ChEBI
CYP2B6
CHEBI:15627
ChEBI
ARA
H+
CYP26B1
TAM
5HIALD
CYP2C9
DEXM
CH3CHO
NADPH
3APAL
H+
H+
H2O
CYP2J2
CYP2B6
H2O
CCl4
CYP2C19
CYP4F3
CHEBI:16716
ChEBI
NADPH
BaP4,5O
NADPH
CHEBI:28509
ChEBI
CHEBI:47266
ChEBI
R-NUL-76433
Reactome
H2O
CHEBI:18276
ChEBI
H+
CYP2F1
NAD+
CYP2C19
H+
CHEBI:81621
ChEBI
H2O2
CYP2A13
NADPH
CYP11B1
P23141
Uniprot
CHEBI:41001
ChEBI
CHEBI:34560
ChEBI
CYP46A1
O00748
Uniprot
H+
H2O
CYP4F2
CHEBI:27958
ChEBI
CHOL
CHEBI:17790
ChEBI
CHEBI:196991
ChEBI
NADPH
CHEBI:3410
ChEBI
CYP3A4
O2
P30838
Uniprot
CYP2S1
H+
CYP2A7
CoA-SH
NADH
20a,22b-DHCHOL
ADH4
CYP2F1
CYP2A7
Cl-
O2
NADPH
CYP4A11
O2
H+
SPM
H2O
NADPH
I4AH
NADPH
VC
CYP2W1
CYP2C9
RXRA
CYP2A13
H2O
CHEBI:29108
ChEBI
NADPH
4CHOL7a,24(S)DONE
CHEBI:27398
ChEBI
O2
O2
P19801
Uniprot
HALO
P07099
Uniprot
AOC2
CHEBI:18295
ChEBI
CYP2F1
O2
ATP
NADP+
O2
CYP2B6
H2O
O2
H+
ALDO
CDCA
NADPH
PGH2
CYP4F11
NADP+
H+
4CHOL7a,12a,27TONE
CYP2F1
NADP+
CTL
ADH1C
P05108
Uniprot
P22570
Uniprot
H2O
H2O
P10109
Uniprot
PHEN
CHEBI:33738
ChEBI
Q6P4F2
Uniprot
CYP4B1
FAD
NADP+
FAD
CYP2B6
CES1
O43174
Uniprot
NADP+
ALDH2
Q6V0L0
Uniprot
Q9NR63
Uniprot
O2
CHEBI:63802
ChEBI
NADP+
CHEBI:50648
ChEBI
11DCORT
CYP51A1
CYP27A1
Losec
NADH
H+
NADPH
H+
CHEBI:83782
ChEBI
NADPH
CHEBI:48926
ChEBI
H+
CTL
CHEBI:15630
ChEBI
BaP4,5-DHD
CYP4F11
CHEBI:16225
ChEBI
CHOL7a,24(S)DIOL
P11766
Uniprot
H2O
CYP3A43
PGH2
H+
O2
4,4DMCHOLtrienol
H2O
CHEBI:16827
ChEBI
CYP3A4
CHEBI:33737
ChEBI
O2
CYP3A43
Q9NWM0-3
Uniprot
CHEBI:27584
ChEBI
CYP19A1
CHEBI:16485
ChEBI
NADP+
CYP4F8
P19099
Uniprot
P20815
Uniprot
P08684
Uniprot
P24462
Uniprot
NADP+
CYP4F22
CYP2A6
H+
H2O2
CYP2A7
H+
FDX1L
H+
ARA
CYP4A11
FDX1L
H2O
NADP+
H2O
Zn2+
3,16DOH-PALM
O2
CYP3A43
Ca2+
CYP2C8
CHEBI:16755
ChEBI
NADPH
Q15788
Uniprot
Q15596
Uniprot
24OH-CHOL
Q96RI1
Uniprot
P19793
Uniprot
H+
CHEBI:16325
ChEBI
FDXR
CYP26A1
CYP4F8
PTXL
CYP2S1
H+
PAOX
H+
H2O
12-HETE
CYP2B6
PGI2
P98187
Uniprot
O2
CHEBI:28834
ChEBI
Q9UNU6
Uniprot
Q16647
Uniprot
Q9HCS2
Uniprot
NADP+
O2
H+
NADPH
NADP+
CYP26C1
O2
H2O
CYP2E1
HOMZ
NADP+
DCA
E1
NADP+
AMP
FDX1
O2
H2O
H2O
CYP2C9
NADP+
HCOOH
NCOA1
O2
CYP7A1
NADPH
CYP2F1
Hist
O2
CYP7B1
ANDST
O2
AFXBO
H2O
H+
CYP2J2
NADP+
CYP2C8
H2O2
NADP+
CYP2D6
ADH5
CYP2C8
CYP2C18
H2O
NADP+
NADPH
NHABP
TAMO
H+
CYP4A22
CYP2C19
CYP3A5
POMC(138-176)
NADPH
CHEBI:17823
ChEBI
CYP4A22
NADP+
O15528
Uniprot
4065146
PubMed
Mitochondrial aldehyde dehydrogenase from human liver. Primary structure, differences in relation to the cytosolic enzyme, and functional correlations.
Hempel J, Kaiser R, Jörnvall H.
CHEBI:15367
ChEBI
ABPH
CHEBI:63911
ChEBI
PPi
Q07973
Uniprot
CAF
NADPH
CYP2C19
CYP2J2
CYP2C8
18HCORST
CHEBI:63998
ChEBI
NADPH
CHEBI:63795
ChEBI
NAD+
CHEBI:37248
ChEBI
CHEBI:31697
ChEBI
CHEBI:16881
ChEBI
NADP+
S-FGSH
O2
SPM
NR1H4
O2
O2
CYP4F3
H2O
O2
NADPH
CYP2A7
CYP2B6
H+
FDXR
CYP3A4
H+
CHEBI:15882
ChEBI
CHEBI:28940
ChEBI
CHEBI:29132
ChEBI
Q6VVX0
Uniprot
SPN
6BHT
CHEBI:17933
ChEBI
NADP+
H2O
18196
PubMed
Two aldehyde dehydrogenases from human liver. Isolation via affinity chromatography and characterization of the isozymes.
Greenfield NJ, Pietruszko R.
O2
CYP4F11
MeOH
DDCX
O2
3AAPNAL
HPHAC
P27338
Uniprot
P21397
Uniprot
CHEBI:27647
ChEBI
Q01740
Uniprot
CYP2C8
24OH-CHOL
CYP2C9
CHEBI:18420
ChEBI
CYP2C19
NASPN
H+
Trichloromethyl
radical
H+
4OH-EST17b
EPHX1
Phenytoin
CHEBI:28790
ChEBI
CYP3A7
CHEBI:15760
ChEBI
CHEBI:15621
ChEBI
CHEBI:16134
ChEBI
CHEBI:16240
ChEBI
CYP2C19
Cu2+
CH3CHO
ISCAL
NADPH
TXA2
CYP2C8
CHEBI:63825
ChEBI
CHEBI:15724
ChEBI
CYP2C19
O2
CHEBI:18139
ChEBI
H+
NADPH
TFAC
CHEBI:50673
ChEBI
NADPH
CHEBI:63904
ChEBI
TrXA3
Paraxanthine
CYP4F22
TYR
CYP4F3
H2O
CYP2S1
CHEBI:63828
ChEBI
H2O
DEXT
Q99518
Uniprot
CYP2A7
CHEBI:41774
ChEBI
H+
H2O
4OH-9cRA
CYP2C19
P31513
Uniprot
CHEBI:16238
ChEBI
O2
O2
NADP+
3AAPNAL
Q6QHF9
Uniprot
9cRA
NADP+
H+
PGG2
O2
O2
CHEBI:15422
ChEBI
CHEBI:15846
ChEBI
CHEBI:16027
ChEBI
PTGIS
3OH-PALM
CHEBI:15343
ChEBI
20OH-LTB4
TBM
H2O2
NADP+
19OH-PGH2
NADPH
NADPH
8,9-EET
H2O
HPTXL
CYP4F8
atRA
4CHOL7a,12aDONE
NH3
CYP4F2
H2O
CH2O
CYP26C1
PREG
H2O2
CYP4F22
FAD
CYP7A1
EtOH
NADP+
CYP2F1
CYP2B6
Phenylacetaldehyde
H2O
CYP2S1
NADP+
CHEBI:18397
ChEBI
CHEBI:50157
ChEBI
CHEBI:17927
ChEBI
O2
CHEBI:16424
ChEBI
NADP+
HCOOH
CHEBI:17312
ChEBI
H2O
H2O
CYP4F2
H2O
CHEBI:30322
ChEBI
VD3
CYP4F22
CHEBI:15746
ChEBI
H+
CHEBI:18090
ChEBI
CHEBI:17148
ChEBI
HCOU
CHEBI:16610
ChEBI
CYP1A1
CYP2E1