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