NADPH
NADP+
TAMO
H+
HPTXL
H2O2
H+
NADP+
H2O
NADPH
Putrescine
NADPH
NADPH
H+
27-hydroxycholesterol
Cytochrome P450
(CYP8B1 based)
This CandidateSet contains sequences identified by William Pearson's analysis of Reactome catalyst entities. Catalyst entity sequences were used to identify analagous sequences that shared overall homology and active site homology. Sequences in this Candidate set were identified in an April 24, 2012 analysis. (Reactome)
Cytochrome P450
(CYP2D6 based)
This CandidateSet contains sequences identified by William Pearson's analysis of Reactome catalyst entities. Catalyst entity sequences were used to identify analagous sequences that shared overall homology and active site homology. Sequences in this Candidate set were identified in an April 24, 2012 analysis. (Reactome)
NADP+
O2
Cytochrome P450
(CYP4F12 based)
This CandidateSet contains sequences identified by William Pearson's analysis of Reactome catalyst entities. Catalyst entity sequences were used to identify analagous sequences that shared overall homology and active site homology. Sequences in this Candidate set were identified in an April 24, 2012 analysis. (Reactome)
AMP
H+
PGH2
NADP+
H2O
NADH
Cytochrome P450
(CYP4F2/4F3 based)
This CandidateSet contains sequences identified by William Pearson's analysis of Reactome catalyst entities. Catalyst entity sequences were used to identify analagous sequences that shared overall homology and active site homology. Sequences in this Candidate set were identified in an April 24, 2012 analysis. (Reactome)
NADP+
Cytochrome P450
(CYP11B1 based)
This CandidateSet contains sequences identified by William Pearson's analysis of Reactome catalyst entities. Catalyst entity sequences were used to identify analagous sequences that shared overall homology and active site homology. Sequences in this Candidate set were identified in an April 24, 2012 analysis. (Reactome)
O2
Cytochrome P450
(CYP8A1 based)
This CandidateSet contains sequences identified by William Pearson's analysis of Reactome catalyst entities. Catalyst entity sequences were used to identify analagous sequences that shared overall homology and active site homology. Sequences in this Candidate set were identified in an April 24, 2012 analysis. (Reactome)
H2O
MTZ
O2
NADPH
H2O
H2O
H2O
Cholesterol
PTXL
H+
NADP+
H+
24-hydroxycholesterol
O2
Molecular characterization of human acetyl-CoA synthetase, an enzyme regulated by sterol regulatory element-binding proteins.
Luong A, Hannah VC, Brown MS, Goldstein JL.
PubMed
10843999
NADPH
H+
H+
FMO2(2-535)
[endoplasmic
reticulum membrane]
CH3CHO
19-hydroxyarachidonic
acid
H+
TES
NADP+
HPALM
O2
CTL
NADPH
POMC(138-176)
NADPH
EST17b
Cholest-5-ene-3beta,7alpha,25-triol
INDOL
4-cholesten-7alpha,
12alpha-diol-3-one
NADP+
H+
CYP17A1
CYP26A1
CYP19A1(2-503)
H+
VD3
NADP+
NADPH
H2O
DDCX
NADPH
LNSOL
O2
H2O
PAOX(2-649)
[peroxisomal matrix]
VC
NADPH
Cytochrome P450
(CYP4B1 based)
This CandidateSet contains sequences identified by William Pearson's analysis of Reactome catalyst entities. Catalyst entity sequences were used to identify analagous sequences that shared overall homology and active site homology. Sequences in this Candidate set were identified in an April 24, 2012 analysis. (Reactome)
CYP1B1
H+
CH2O
cis-EET
O2
NADPH
NADP+
H2O
NADPH
H2O
NADP+
NADPH
MAOA [mitochondrial
outer membrane]
H2O
MIND
H2O
O2
NADP+
H2O
H2O
O2
O2
HatRA
HDBQ
NADP+
NADPH
FAD [endoplasmic
reticulum membrane]
Cytochrome P450
(CYP4F8 based)
This CandidateSet contains sequences identified by William Pearson's analysis of Reactome catalyst entities. Catalyst entity sequences were used to identify analagous sequences that shared overall homology and active site homology. Sequences in this Candidate set were identified in an April 24, 2012 analysis. (Reactome)
H2
NADP+
FMO1 [endoplasmic
reticulum lumen]
CYP1A2
O2
NHABP
Cytochrome P450
(CYP2F1 based)
This CandidateSet contains sequences identified by William Pearson's analysis of Reactome catalyst entities. Catalyst entity sequences were used to identify analagous sequences that shared overall homology and active site homology. Sequences in this Candidate set were identified in an April 24, 2012 analysis. (Reactome)
NADP+
FAD [mitochondrial
outer membrane]
NADP+
H+
NADP+
NADPH
NADP+
Cytochrome P450
(CYP4A11 based)
This CandidateSet contains sequences identified by William Pearson's analysis of Reactome catalyst entities. Catalyst entity sequences were used to identify analagous sequences that shared overall homology and active site homology. Sequences in this Candidate set were identified in an April 24, 2012 analysis. (Reactome)
H+
20alpha,22beta
dihydroxycholesterol
NADP+
H2O
H2O
NADPH
4-cholesten-7alpha,12alpha,24(S)-triol-3-one
NADP+
NADP+
H+
FAD [endoplasmic
reticulum membrane]
HCOOH
H+
NADPH
H2O
H2O
ChEBI
CHEBI:17813
ChEBI
CHEBI:17026
ChEBI
CHEBI:17650
ChEBI
CHEBI:1294
NADPH
Cholesterol
3-acetamidopropanal
Uniprot
P05093
HcRA
CYP46A1
H2O2
ChEBI
CHEBI:16827
NADP+
ChEBI
CHEBI:34310
O2
NADPH
ChEBI
CHEBI:16113
O2
Uniprot
Q16850
CYP26B1
ChEBI
CHEBI:16469
ChEBI
CHEBI:16581
H+
H2O
Cytochrome P450
(CYP7B1 based)
This CandidateSet contains sequences identified by William Pearson's analysis of Reactome catalyst entities. Catalyst entity sequences were used to identify analagous sequences that shared overall homology and active site homology. Sequences in this Candidate set were identified in an April 24, 2012 analysis. (Reactome)
ATP
ChEBI
CHEBI:17263
O2
5HT
ChEBI
CHEBI:16474
H2O
H2O
1,24,25-trihydroxyvitamin
D3
ChEBI
CHEBI:15378
ChEBI
CHEBI:18009
H+
PEA
C2H4
NADPH
3,16-dihydroxypalmitate
H2O
ChEBI
CHEBI:15552
EtO
ChEBI
CHEBI:15377
O2
ChEBI
CHEBI:37623
ChEBI
CHEBI:16521
ChEBI
CHEBI:42977
Uniprot
P05108
ChEBI
CHEBI:16908
ChEBI
CHEBI:15422
ChEBI
CHEBI:15846
CH3CHO
ChEBI
CHEBI:16027
ChEBI
CHEBI:39567
ChEBI
CHEBI:30805
Reactome
REACT_14302
ChEBI
CHEBI:15843
H+
ChEBI
CHEBI:48825
CoA-SH
ChEBI
CHEBI:16973
Uniprot
P05091
ChEBI
CHEBI:15366
Uniprot
Q9NR19
O2
Uniprot
P00352
CYP27B1(?-508)
The start coordinate is not yet known (Reactome)
O2
O2
ChEBI
CHEBI:15351
H+
ABPH
ChEBI
CHEBI:15346
Reactome
REACT_21845
H2O
ChEBI
CHEBI:29888
ChEBI
CHEBI:4470
Uniprot
Q9NUB1
ChEBI
CHEBI:15554
ChEBI
CHEBI:16236
ChEBI
CHEBI:10545
Uniprot
P24557
Losec
2CEO
H2O2
LTB4
NADP+
11-deoxycortisol
O2
Uniprot
P23219
ChEBI
CHEBI:15646
Uniprot
P01189
Arachidonic acid
ChEBI
CHEBI:29133
ChEBI
CHEBI:15647
NADP+
CH3CHO
4-cholesten-7alpha,27-diol-3-one
H+
DOC
Uniprot
Q96SQ9
18-hydroxyarachidonate
Reactome
REACT_160369
Reactome
REACT_161337
EtOH
H+
Reactome
REACT_160403
ChEBI
CHEBI:26355
H2O
PGH2
NADP+
6BHT
DEXM
NADPH
O2
O2
ChEBI
CHEBI:45863
9cisRA
MAOB [mitochondrial
outer membrane]
ChEBI
CHEBI:6532
ChEBI
CHEBI:63905
ChEBI
CHEBI:27510
ChEBI
CHEBI:63840
Uniprot
Q9HB55
H2O
O2
Reactome
REACT_165596
SPM
N-demethylated
loperamide
Uniprot
Q9NWM0
Reactome
REACT_164947
Uniprot
Q7Z449
PhOH
H+
ChEBI
CHEBI:16580
ChEBI
CHEBI:63804
ChEBI
CHEBI:2505
ChEBI
CHEBI:25858
ChEBI
CHEBI:16842
Reactome
REACT_165042
Reactome
REACT_164982
H+
O2
Reactome
REACT_164913
NADP+
Reactome
REACT_165034
H+
H2O
Reactome
REACT_165394
O2
ChEBI
CHEBI:29129
ChEBI
CHEBI:5615
CCl4
H2O
Uniprot
P05177
CH2O
ChEBI
CHEBI:1784
Reactome
REACT_164659
ChEBI
CHEBI:27732
Reactome
REACT_165338
Reactome
REACT_165182
Reactome
REACT_165424
CPM
Reactome
REACT_164521
NH3
NASPN
ChEBI
CHEBI:17996
Reactome
REACT_4348
ChEBI
CHEBI:29138
NADP+
ChEBI
CHEBI:27385
Reactome
REACT_165599
Reactome
REACT_125551
NADP+
ChEBI
CHEBI:46195
Reactome
REACT_165418
Reactome
REACT_164482
PGI2
O2
Reactome
REACT_165609
E1
Reactome
REACT_165074
ChEBI
CHEBI:63590
ChEBI
CHEBI:19138
ChEBI
CHEBI:17347
3-acetamidopropanal
ChEBI
CHEBI:63799
ChEBI
CHEBI:64043
H+
ChEBI
CHEBI:28324
Uniprot
P08686
Uniprot
Q9Y6A2
Reactome
REACT_164514
ChEBI
CHEBI:17998
Reactome
REACT_165317
ChEBI
CHEBI:17703
Reactome
REACT_165430
Reactome
REACT_165169
H2O
Cytochrome P450
(CYP26A1 based)
This CandidateSet contains sequences identified by William Pearson's analysis of Reactome catalyst entities. Catalyst entity sequences were used to identify analagous sequences that shared overall homology and active site homology. Sequences in this Candidate set were identified in an April 24, 2012 analysis. (Reactome)
ChEBI
CHEBI:34477
O2
CH3COO-
CAF
ChEBI
CHEBI:1864
Uniprot
P04798
ChEBI
CHEBI:27999
ChEBI
CHEBI:63800
ChEBI
CHEBI:28477
ChEBI
CHEBI:17899
ChEBI
CHEBI:63839
ChEBI
CHEBI:48333
NADPH
ChEBI
CHEBI:63838
NAD+
DEXT
ChEBI
CHEBI:34665
ChEBI
CHEBI:4026
ChEBI
CHEBI:63859
H2O
ChEBI
CHEBI:28794
TES
ChEBI
CHEBI:18153
ChEBI
CHEBI:62845
H2O
ChEBI
CHEBI:17500
1,25-dihydroxyvitamin
D3
O2
ChEBI
CHEBI:30751
O2
H2O2
ChEBI
CHEBI:37640
ChEBI
CHEBI:28750
NADPH
ChEBI
CHEBI:27561
ChEBI
CHEBI:7772
O2
ChEBI
CHEBI:9171
H2O
ChEBI
CHEBI:2504
ALDH2 [mitochondrial
matrix]
ChEBI
CHEBI:8107
ATP
Uniprot
Q02318
25-hydroxycholesterol
Uniprot
Q16678
H+
HALO
Uniprot
Q9NYL5
ChEBI
CHEBI:16422
Uniprot
P11511
H2O
NADP+
H+
Cholesterol
NADPH
Homo sapiens
NADPH
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.Original Pathway at Reactome: http://www.reactome.org/PathwayBrowser/#DB=gk_current&FOCUS_SPECIES_ID=48887&FOCUS_PATHWAY_ID=211945 (WikiPathways-description)
24-hydroxycholesterol
ChEBI
CHEBI:63912
ChEBI
CHEBI:15379
ChEBI
CHEBI:15627
NADPH
NASPM
SMOX
20oh-LTB4
CORST
H+
APrOH
NADPH
NADP+
SPM
H2O
CYP51A1
Cholest-5-ene-3beta,7alpha,24(S)-triol
Cytochrome P450
(CYP2W1 based)
This CandidateSet contains sequences identified by William Pearson's analysis of Reactome catalyst entities. Catalyst entity sequences were used to identify analagous sequences that shared overall homology and active site homology. Sequences in this Candidate set were identified in an April 24, 2012 analysis. (Reactome)
Cytochrome P450
(CYP4F11 based)
This CandidateSet contains sequences identified by William Pearson's analysis of Reactome catalyst entities. Catalyst entity sequences were used to identify analagous sequences that shared overall homology and active site homology. Sequences in this Candidate set were identified in an April 24, 2012 analysis. (Reactome)
Phenylacetaldehyde
FAD [endoplasmic
reticulum membrane]
TFAC
H2O
ChEBI
CHEBI:15882
ChEBI
CHEBI:47266
NADP+
ChEBI
CHEBI:16716
ChEBI
CHEBI:18276
ChEBI
CHEBI:28509
NH3
7
alpha-hydroxycholesterol
NADPH
NADP+
ACSS2
Phenytoin
Cytochrome P450
(CYP2B6 based)
This CandidateSet contains sequences identified by William Pearson's analysis of Reactome catalyst entities. Catalyst entity sequences were used to identify analagous sequences that shared overall homology and active site homology. Sequences in this Candidate set were identified in an April 24, 2012 analysis. (Reactome)
O2
NH3
NADPH
HBr
H2O
Two aldehyde dehydrogenases from human liver. Isolation via affinity chromatography and characterization of the isozymes.
Greenfield NJ, Pietruszko R.
PubMed
18196
H2O
O2
C6H6
Cl-
NADP+
NADPH
CORT
O2
NADP+
H+
NADP+
H2O
NADPH
NADP+
H2O
O2
Ac-CoA
O2
HCPM
NADPH
H+
NADPH
NADP+
O2
4-cholesten-7alpha,24(S)-diol-3-one
4,4-dimethylcholesta-8(9),14,24-trien-3beta-ol
NADP+
H2O
NADP+
NADP+
NADPH
alcohol
dehydrogenase
complex
H2O
HTOLB
NADPH
NADP+
HIALD
O2
O2
O2
NADP+
MTZ-SOX
H2O
O2
NADPH
NADPH
H2O
PREG
P4
NADPH
CDL
CYP2S1
H+
HPHAC
O2
Mg2+ [endoplasmic
reticulum membrane]
17alpha-hydroxypregnenolone
Acetaminophen (TN
TYLENOL)
Reactome
REACT_164168
Reactome
REACT_164281
CoA-SH
Reactome
REACT_164336
H+
Reactome
REACT_165595
NADP+
H2O
NADPH
H2O
H+
3MEIN
H2O
O2
NADP+
H2O
19-OH PGH2
Mitochondrial aldehyde dehydrogenase from human liver. Primary structure, differences in relation to the cytosolic enzyme, and functional correlations.
Hempel J, Kaiser R, Jörnvall H.
PubMed
4065146
ACSS1
TAM
NADP+
H+
H2O
H2O2
Cytochrome P450
(CYP2E1 based)
This CandidateSet contains sequences identified by William Pearson's analysis of Reactome catalyst entities. Catalyst entity sequences were used to identify analagous sequences that shared overall homology and active site homology. Sequences in this Candidate set were identified in an April 24, 2012 analysis. (Reactome)
Aflatoxin
exo-8,9-oxide
FAD [peroxisomal
matrix]
H+
CYP39A1
Cytochrome P450
(CYP7A1 based)
This CandidateSet contains sequences identified by William Pearson's analysis of Reactome catalyst entities. Catalyst entity sequences were used to identify analagous sequences that shared overall homology and active site homology. Sequences in this Candidate set were identified in an April 24, 2012 analysis. (Reactome)
omega-Hydroxydodecanoic
acid
NADP+
H+
CYP27A1
H2O2
Oxindole
Cytochrome P450
(CYP26C1 based)
This CandidateSet contains sequences identified by William Pearson's analysis of Reactome catalyst entities. Catalyst entity sequences were used to identify analagous sequences that shared overall homology and active site homology. Sequences in this Candidate set were identified in an April 24, 2012 analysis. (Reactome)
O2
H2O
NADP+
TXA2
O2
NADPH
O2
H2O
NADPH
H2O
Cytochrome P450
(CYPIIIA4 based)
This CandidateSet contains sequences identified by William Pearson's analysis of Reactome catalyst entities. Catalyst entity sequences were used to identify analagous sequences that shared overall homology and active site homology. Sequences in this Candidate set were identified in an April 24, 2012 analysis. (Reactome)
Cytochrome P450
(CYP2C9 based)
This CandidateSet contains sequences identified by William Pearson's analysis of Reactome catalyst entities. Catalyst entity sequences were used to identify analagous sequences that shared overall homology and active site homology. Sequences in this Candidate set were identified in an April 24, 2012 analysis. (Reactome)
H2O
H+
O2
O2
ALDH1A1 [cytosol]
TMA
H2O
Purification and partial characterization of aldehyde dehydrogenase from human erythrocytes.
Inoue K, Nishimukai H, Yamasawa K.
PubMed
224930
O2
H+
LPAM
NADPH
HOMZ
CYP2U1
4-Androstene-3,
17-dione
H+
12-hydroxy-5,8,10,14-eicosatetraenoic
acid
TYR
NADPH
4-OH-Estradiol
AFTB1
O2
Pregnenolone
HPHT
e-
H2O
NADP+
ChEBI
CHEBI:63911
NAD+
ISCAL
ChEBI
CHEBI:50648
ChEBI
CHEBI:63802
EtOH
Uniprot
Q07973
NADPH
Uniprot
O15528
O2
NADH
O2
H+
O2
H2O
Cytochrome P450
(CYP11B2 based)
This CandidateSet contains sequences identified by William Pearson's analysis of Reactome catalyst entities. Catalyst entity sequences were used to identify analagous sequences that shared overall homology and active site homology. Sequences in this Candidate set were identified in an April 24, 2012 analysis. (Reactome)
NADP+
heme b [endoplasmic
reticulum membrane]
H2O
NADPH
ChEBI
CHEBI:63795
Cytochrome P450
(CYP2A13 based)
This CandidateSet contains sequences identified by William Pearson's analysis of Reactome catalyst entities. Catalyst entity sequences were used to identify analagous sequences that shared overall homology and active site homology. Sequences in this Candidate set were identified in an April 24, 2012 analysis. (Reactome)
ChEBI
CHEBI:15367
ChEBI
CHEBI:63998
FMO3 [endoplasmic
reticulum membrane]
Uniprot
O43174
PPi
Uniprot
Q9NR63
NADH
Arachidonic acid
NADPH
H2O
NABQI
NADP+
HCOOH
ChEBI
CHEBI:29132
H+
ChEBI
CHEBI:17933
ChEBI
CHEBI:28940
ChEBI
CHEBI:17823
DSQ
Uniprot
Q6VVX0
H+
Arachidonic acid
4-cholesten-7alpha-ol-3-one
CYP3A43
O2
H+
H+
NAD+
H2O
H+
CYP24A1
HCOU
6BHT
Uniprot
Q01740
SPN
ChEBI
CHEBI:18420
Uniprot
Q99518
ChEBI
CHEBI:63828
ChEBI
CHEBI:16238
PGG2
H+
H+
CYP1A1
NADP+
NADPH
H+
NADP+
ChEBI
CHEBI:16240
PPi
NADPH
Uniprot
P27338
ChEBI
CHEBI:16134
ChEBI
CHEBI:27647
H2O
Uniprot
P21397
TBM
H+
H+
O2
ChEBI
CHEBI:63904
O2
ChEBI
CHEBI:37248
CYP2R1
ChEBI
CHEBI:50673
PTGS1 [endoplasmic
reticulum membrane]
ChEBI
CHEBI:31697
ChEBI
CHEBI:16881
TMAO
Ac-CoA
H+
CYP21A2
NADP+
H+
TBXAS1
Trichloromethyl
radical
atRA
NADPH
ChEBI
CHEBI:41774
Uniprot
P31513
O2
ChEBI
CHEBI:15724
ChEBI
CHEBI:63825
ChEBI
CHEBI:18139
H2O
Cytochrome P450
(CYP3A5 based)
This CandidateSet contains sequences identified by William Pearson's analysis of Reactome catalyst entities. Catalyst entity sequences were used to identify analagous sequences that shared overall homology and active site homology. Sequences in this Candidate set were identified in an April 24, 2012 analysis. (Reactome)
O2
Cytochrome P450
(CYP2C18 based)
This CandidateSet contains sequences identified by William Pearson's analysis of Reactome catalyst entities. Catalyst entity sequences were used to identify analagous sequences that shared overall homology and active site homology. Sequences in this Candidate set were identified in an April 24, 2012 analysis. (Reactome)
COUM
ChEBI
CHEBI:18090
Cytochrome P450
(CYP3A7 based)
This CandidateSet contains sequences identified by William Pearson's analysis of Reactome catalyst entities. Catalyst entity sequences were used to identify analagous sequences that shared overall homology and active site homology. Sequences in this Candidate set were identified in an April 24, 2012 analysis. (Reactome)
ChEBI
CHEBI:15343
Uniprot
Q6QHF9
ChEBI
CHEBI:16610
Cytochrome P450
(CYP2A3 based)
This CandidateSet contains sequences identified by William Pearson's analysis of Reactome catalyst entities. Catalyst entity sequences were used to identify analagous sequences that shared overall homology and active site homology. Sequences in this Candidate set were identified in an April 24, 2012 analysis. (Reactome)
ChEBI
CHEBI:17148
H2O
H2O
AMP
O2
H+
4-cholesten-7alpha,12alpha,27-triol-3-one
NADPH
Cytochrome P450
(CYP2J2 based)
This CandidateSet contains sequences identified by William Pearson's analysis of Reactome catalyst entities. Catalyst entity sequences were used to identify analagous sequences that shared overall homology and active site homology. Sequences in this Candidate set were identified in an April 24, 2012 analysis. (Reactome)
H+
CH3COO-
Paraxanthine
NADP+
O2
H+
NADPH
ChEBI
CHEBI:15621
ChEBI
CHEBI:15760
DOC
O2
ChEBI
CHEBI:50157
ChEBI
CHEBI:28790
ChEBI
CHEBI:18397
CYP11A1
Cytochrome P450
(CYP2C8 based)
This CandidateSet contains sequences identified by William Pearson's analysis of Reactome catalyst entities. Catalyst entity sequences were used to identify analagous sequences that shared overall homology and active site homology. Sequences in this Candidate set were identified in an April 24, 2012 analysis. (Reactome)
ChEBI
CHEBI:16424
ChEBI
CHEBI:17927
ChEBI
CHEBI:17312
ChEBI
CHEBI:30322
Cytochrome P450
(CYP2C19 based)
This CandidateSet contains sequences identified by William Pearson's analysis of Reactome catalyst entities. Catalyst entity sequences were used to identify analagous sequences that shared overall homology and active site homology. Sequences in this Candidate set were identified in an April 24, 2012 analysis. (Reactome)
NADPH
ChEBI
CHEBI:15746
FAD [mitochondrial
outer membrane]
H2O
O2
H+
NADPH