ADH7 O2 CYP4V2 CHOL SMOX-3 H+ 4OH-9cRA CYP4F3 TAM NADP+ H+ PREG 12OH-DDCX CYP4A11 H+ O2 ABPH H2O2 NADPH H+ O2 NADP+ CYP2E1 H2O CYP4B1 CH3CHO H+ Cu2+ O2 CYP4A11 O2 NADPH NADP+ CYP2A13 e- H+ CYP4F2 NADPH CYP3A7 Cl- CYP2W1 18OH-ARA CYP2C19 CYP2C8 NADP+ CYP2C19 NADPH H2O CYP450 (red.) 4CHOL7a,24(S)DONE CYP2A7 CYP2A6 CYP19A1 5,6-EET CYP4F11 CYP4F3 ALDH2 CYP4F22 DDCX H2O CHOL7a,24(S)DIOL H2O NADPH H2O Paraxanthine NADP+ FAD H+ NAD+ H2O2 CYP2D6 POMC(138-176) H2O NADPH 4CHOL7aOLONE NADPH CH2O NADP+ 19OH-PGH2 NADPH CYP2A13 4-ethoxyaniline CYP4F11 O2 H+ 6BHT O2 H+ HALO ACV CYP2F1 HOMZ ARA NADP+ PPi CYP2E1 CYP2W1 O2 CYP2C19 O2 H2O DSQ H2O NADPH H+ CYP2C19 H2O H2O FDXR CYP2F1 NADPH NADP+ CYP4B1 H2O CYP2F1 O2 NADP+ CYP4A11 NADPH H+ 6BHT NADPH ACSS2 NADP+ TES H+ TYR (2Fe-2S)(1+) H+ EST17b Zn2+ CTL NADPH NCOA1 TBXAS1 CES1 CDL NADP+ CYP11B1 CYP3A43 H2O NADP+ NADPH NADPH DHA LPAM H2O CYP3A4 NADPH CYP26C1 CYP4B1 NADP+ 24OH-CHOL AADAC H2O AOC2 Q6ZWL3 Uniprot ALDO P16435 Uniprot CHEBI:4057 ChEBI CHEBI:4058 ChEBI H+ NADH 224930 Purification and partial characterization of aldehyde dehydrogenase from human erythrocytes. Inoue K, Nishimukai H, Yamasawa K. PubMed CHEBI:31932 ChEBI Zn2+ BPHL NH3 HPHAC H2O NADH CHEBI:46640 ChEBI CYP2C19 CYP2D6 CHEBI:72790 ChEBI CHEBI:36005 ChEBI Q96DG6 Uniprot CHEBI:48416 ChEBI CYP2C18 P22760 Uniprot O2 NADPH O2 NADP+ CYP2S1 CYP2C19 4CHOL7a,12a,27TONE H2O TrXA3 LTB4 COUM CHEBI:35854 ChEBI CHEBI:2453 ChEBI 19HETE 18HCORST Q86WA6 Uniprot CXPA 11DCORST CHEBI:16414 ChEBI Q16853 Uniprot CHEBI:17169 ChEBI H+ O2 CYP26A1 NADP+ NADP+ CYP2D6 ADH1B NADP+ CHEBI:8050 ChEBI H+ P30837 Uniprot H2O2 NADP+ NADPH CHEBI:85505 ChEBI CYP2A7 atRA CHEBI:40574 ChEBI CHEBI:17650 ChEBI CHEBI:1294 ChEBI CHEBI:34310 ChEBI CHEBI:16581 ChEBI NADPH 5HT H2O 3AAPNAL CHEBI:17813 ChEBI 4HPCP O2 CYP4F22 CYP3A4 H2O H2O 14,15-EET CHEBI:17026 ChEBI CYP2E1 TMA NADPH CHEBI:28694 ChEBI Q16850 Uniprot 3MEIN CHEBI:16469 ChEBI CHEBI:40538 ChEBI CHEBI:62845 ChEBI O2 O75106 Uniprot CHEBI:17500 ChEBI NADP+ H+ NADPH CYP2C9 CYP3A5 CHEBI:16113 ChEBI CYP2S1 H+ CYP2B6 NADPH CYP11A1 CYP2C8 ADH1C CHEBI:17263 ChEBI CHEBI:16474 ChEBI O2 CHEBI:15378 ChEBI CHEBI:18009 ChEBI HCPM NADP+ CYP4F2 NADPH H+ Cu2+ O2 NADPH CHEBI:15552 ChEBI CDCA O2 CYP4F11 CHEBI:15377 ChEBI CYP2S1 CHEBI:16521 ChEBI P05093 Uniprot CYP2A13 CHEBI:42977 ChEBI CYP4A11 H2O H2O CHEBI:37623 ChEBI H+ H2O P05091 Uniprot CHEBI:15351 ChEBI DEXM CHEBI:15346 ChEBI H2O CHEBI:16908 ChEBI CHEBI:30805 ChEBI CHEBI:34157 ChEBI H2O CYP2C9 CHEBI:34130 ChEBI NADPH HCOOH CHEBI:34490 ChEBI NADPH CHEBI:34450 ChEBI 4OH-EST17b H2O CHEBI:16973 ChEBI Mg2+ CYP4B1 P00352 Uniprot FAD HPTXL H2O CHEBI:16236 ChEBI H2O CHEBI:29888 ChEBI H2O H+ NADH P07327 Uniprot CYP2F1 CYP2E1 Q9NR19 Uniprot PTGS1 CYP2S1 CHEBI:15366 ChEBI CYP3A43 P00326 Uniprot H2O P00325 Uniprot H2O AOC1 P28332 Uniprot P08319 Uniprot NADPH CHEBI:15554 ChEBI CHEBI:10545 ChEBI NADP+ CHEBI:29105 ChEBI P24557 Uniprot NADP+ NADP+ H2O H+ CYP1B1 CYP24A1 AOC3 CYP11A1 O2 I4AH CYP2C9 PhOH O2 EPHX1 CHEBI:15647 ChEBI H2O CYP2C8 CHEBI:4470 ChEBI CYP4F2 NADPH CHEBI:29133 ChEBI H+ P40394 Uniprot H2O Q9NUB1 Uniprot INDOL MeOH CYP7B1 4065146 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 TFAC 4OH-atRA O2 H+ P4 O2 CH3CHO O75881 Uniprot CHEBI:26355 ChEBI CYP4F3 CYP2A7 P23219 Uniprot P01189 Uniprot CHEBI:15646 ChEBI H+ NADP+ CHOL3b,7a,25TRIOL NADPH CYP4F2 O2 CYP2C18 CHEBI:27510 ChEBI MAOB NADP+ CORST CHEBI:63905 ChEBI H2O CHEBI:8107 ChEBI CHEBI:63840 ChEBI NADP+ CYP2J2 CHEBI:6532 ChEBI P22680 Uniprot H2O MTZ CYP51A1 P20813 Uniprot NADP+ FAD P05181 Uniprot FAD P10632 Uniprot CYP4A22 Losec CYP4F3 P33261 Uniprot FDX1 CYP2C19 CHEBI:16842 ChEBI H+ H+ H2O H+ CHEBI:45863 ChEBI H2O CHEBI:63804 ChEBI ISCAL CoA-SH CHEBI:30725 ChEBI 7 alpha-hydroxycholesterol Hist CHEBI:25858 ChEBI EtOH NADP+ O2 P11712 Uniprot CYP2A13 P10635 Uniprot 18196 Two aldehyde dehydrogenases from human liver. Isolation via affinity chromatography and characterization of the isozymes. Greenfield NJ, Pietruszko R. PubMed Q96SQ9 Uniprot CHOL P24903 Uniprot P11509 Uniprot H+ ADH6 Ac-CoA CYP2F1 C2H4 H+ CHEBI:5615 ChEBI P05177 Uniprot NADPH CHEBI:1784 ChEBI CHEBI:27732 ChEBI P33260 Uniprot CHEBI:16580 ChEBI Q9HB55 Uniprot NADP+ O2 CYP2U1 NADP+ P20853 Uniprot Q16696 Uniprot NADP+ OM Q7Z449 Uniprot H+ 3,16DOH-PALM CHEBI:27385 ChEBI CHEBI:17996 ChEBI CHEBI:46195 ChEBI CHEBI:29138 ChEBI P13584 Uniprot Q02928 Uniprot CHEBI:29129 ChEBI H2O P51589 Uniprot O2 Q8TAV3 Uniprot NADP+ 9cRA Q5TCH4 Uniprot PGH2 H2O FMO2 P78329 Uniprot O2 CHEBI:19138 ChEBI CHEBI:39567 ChEBI CHEBI:63799 ChEBI ADH5 H2O CHEBI:63590 ChEBI CHEBI:17347 ChEBI CYP2E1 Q9Y6A2 Uniprot H2O CYP2S1 CHEBI:17998 ChEBI O2 HPHT CHEBI:17703 ChEBI Phenytoin Q08477 Uniprot CHEBI:28477 ChEBI NADP+ Q6NT55 Uniprot CHEBI:63839 ChEBI P15538 Uniprot Q9HBI6 Uniprot ALDH1B1 NADP+ CHEBI:64043 ChEBI H2O CHEBI:34477 ChEBI O2 CHEBI:1864 ChEBI P04798 Uniprot CHEBI:27999 ChEBI NH3 CHEBI:17899 ChEBI Acetaminophen (TN TYLENOL) CHEBI:48333 ChEBI FDX1L CHEBI:63838 ChEBI CYP7A1 CYP2D6 CHEBI:15843 ChEBI CYP4F8 CHEBI:48825 ChEBI TAMO H2O2 CYP26C1 CHEBI:4026 ChEBI CHEBI:63859 ChEBI CYP2A7 CHEBI:63800 ChEBI O2 SPM CYP2A13 CYP2C8 NADPH CHEBI:18153 ChEBI CHEBI:34665 ChEBI PREG CYP2C8 NADPH CHOL CYP2B6 CHEBI:37640 ChEBI BaP4,5-DHD 20OH-LTB4 CHEBI:28750 ChEBI H2O ADH1A Q02318 Uniprot CHEBI:30751 ChEBI Q16678 Uniprot CHEBI:9171 ChEBI CYP3A5 CHEBI:27561 ChEBI CYP3A7 AMP CYP3A7 CHEBI:28794 ChEBI CYP2B6 H+ CYP4A22 CYP2C18 CYP2C9 CHEBI:7772 ChEBI CHEBI:2504 ChEBI 11DCORT CYP2B6 CHEBI:16422 ChEBI P11511 Uniprot NADP+ H+ NADPH TYR CYP2C9 O2 P08686 Uniprot NADP+ CMBL CHEBI:28324 ChEBI ACSS1 Q9NYL5 Uniprot PTXL CYP2B6 NADPH O2 H+ CCl4 BEG 2CEO Ca2+ NADPH BZAL CYP21A2 H2O H2O Homo sapiens Pathway is converted from Reactome id: (Reactome Converter) 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) Phase 1 - Functionalization of compounds CYP2E1 CHEBI:63912 ChEBI 24OH-CHOL CHEBI:15379 ChEBI CHEBI:15627 ChEBI H+ NASPN CYP2J2 CYP2S1 CYP2A6 NADPH H2O O2 PAOX H+ O2 H+ O2 RXRA NADPH CYP3A43 H2O2 H2O NADPH Oxindole H2O2 CHEBI:16716 ChEBI CYP17A1 CHEBI:28509 ChEBI NADPH CHEBI:47266 ChEBI R-NUL-76433 Reactome CHEBI:18276 ChEBI CORT SPN CYP2J2 CYP2C8 LNSOL CHEBI:81621 ChEBI CYP2D6 O2 4CHOL7a,12a,24(S)TONE CYP2J2 FAD P23141 Uniprot H+ CHEBI:41001 ChEBI NAD+ CHEBI:34560 ChEBI O00748 Uniprot H+ POR L-Val H2O CYP2A13 O2 NADPH O2 H+ CHEBI:27958 ChEBI CYP2F1 TMAO CHEBI:17790 ChEBI ALDH3A1 20OH-TrXA3 NADP+ CHEBI:196991 ChEBI CHEBI:3410 ChEBI P30838 Uniprot H+ H2 TBM MTZ-SOX CTLA AFB1 BaP4,5O NADPH NADP+ H+ NADP+ H+ H2O CYP2A7 HCOOH H2O H+ CHEBI:29108 ChEBI CHEBI:27398 ChEBI P19801 Uniprot P07099 Uniprot CHEBI:18295 ChEBI CYP2E1 ADH4 NADPH CYP2S1 CYP3A43 CYP4F11 CoA-SH CYP2C9 FAD NADPH PTCN VC P05108 Uniprot FDXR P22570 Uniprot P10109 Uniprot CYP2C8 H2O H+ CHEBI:33738 ChEBI H2O Q6P4F2 Uniprot 10843999 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 NHABP PTGIS CYP4F11 H+ CYP11B2 O43174 Uniprot CYP2J2 Q6V0L0 Uniprot CYP11B2 Q9NR63 Uniprot CHEBI:63802 ChEBI CHEBI:50648 ChEBI CAF O2 NH3 H+ NADP+ CH3COOH CHEBI:83782 ChEBI CYP450 (ox.) CHEBI:48926 ChEBI H+ CHEBI:15630 ChEBI PTGIS CHEBI:16225 ChEBI H+ P11766 Uniprot PGG2 O2 CYP2D6 HDoHE H+ CYP4F2 CYP2D6 H2O CYP2C19 CHEBI:16827 ChEBI CHEBI:33737 ChEBI CYP4F22 H2O 3AAPNAL NADP+ O2 Q9NWM0-3 Uniprot H+ CHEBI:27584 ChEBI NADH CHEBI:16485 ChEBI CYP3A4 H2O H2O2 H2O HBr NR1H4 H2O P19099 Uniprot P20815 Uniprot CYP4A22 Phenylacetaldehyde NASPM P08684 Uniprot CPM P24462 Uniprot ATP O2 CYP2A13 CYP4F22 O2 CYP4F22 CYP2A7 Trichloromethyl radical 11DCORST CYP2A7 CYP2C9 O2 O2 HDBQ H2O acetyl group CHEBI:16755 ChEBI H+ Q15788 Uniprot Q15596 Uniprot Q96RI1 Uniprot CYP4F12 CYP4F8 H2O P19793 Uniprot CHEBI:16325 ChEBI NADP+ H+ H+ NADPH H2O 11,12-EET H2O O2 O2 CYP7A1 ARA NADPH CYP2A6 NADPH 17aHPREG VD3 NCOA2 P98187 Uniprot ARA CHEBI:28834 ChEBI Q9UNU6 Uniprot AFXBO Q16647 Uniprot Q9HCS2 Uniprot H2O NADP+ TES 4CHOL7a,27DONE O2 CYP2C8 4HPAA NADP+ TXA2 CH3COO- LCHA NADPH H2O H+ 20OH-LTB4 CYP2R1 NADPH HCOU NADPH NADP+ heme b NADP+ Ca2+ 4CHOL7a,12aDONE CYP2C9 NADP+ NADPH H2O S-FGSH NH3 EtOH CYP2B6 CYP4F12 CYP2F1 NADP+ (2Fe-2S)2+ NADPH O2 O2 CYP2C8 CYP27A1 O2 CYP1A1 CYP39A1 O2 H+ H+ H2O NADPH PEA O2 O2 E1 O2 H2O CYP1A2 H2O CHEBI:17823 ChEBI CYP2F1 BZAM O2 O15528 Uniprot CHEBI:15367 ChEBI H2O CHEBI:63911 ChEBI Q07973 Uniprot NADP+ H2O NADP+ H2O MIND H+ 4,4DMCHtOL FMO1 CYP2C19 CYP2A6 CHEBI:63998 ChEBI CYP2A7 CHEBI:63795 ChEBI CYP3A5 CYP8B1 H+ S-HMGSH CHEBI:37248 ChEBI H2O 27OH-CHOL CHEBI:31697 ChEBI NADP+ CHEBI:16881 ChEBI C6H6 CYP2S1 N-demethylated loperamide H+ 3APAL NAD+ LTB4 CYP4A22 ALDH1A1 O2 CYP2A7 NABQI EtO 20a,22b-DHCHOL CYP4A22 ATP O2 CYP2E1 H2O NADPH CYP26B1 H+ CHEBI:15882 ChEBI NH3 H2O CHEBI:28940 ChEBI CHEBI:29132 ChEBI NADPH CYP2A13 H+ Q6VVX0 Uniprot CHEBI:17933 ChEBI H2O NADP+ NADPH HTOLB FMO3 H+ CH3CHO H+ NADPH CYP2F1 NADPH CYP4F3 CYP4F8 H+ NADP+ P27338 Uniprot H2O P21397 Uniprot FDX1 CHEBI:27647 ChEBI Q01740 Uniprot CHEBI:18420 ChEBI CYP2B6 ANDST NADP+ H+ NADP+ O2 CYP46A1 COCN 8,9-EET CHEBI:28790 ChEBI NADP+ NADP+ CYP2C9 CHEBI:15760 ChEBI PGI2 CHEBI:15621 ChEBI CHEBI:16134 ChEBI Ac-CoA The start coordinate is not yet known (Reactome) CYP27B1(?-508) CHEBI:16240 ChEBI H2O2 CYP2E1 SPM CHEBI:63825 ChEBI CHEBI:15724 ChEBI 25OH-CHOL O2 CHEBI:18139 ChEBI CYP2C18 NAD+ CHEBI:50673 ChEBI DCA CHEBI:63904 ChEBI H+ CYP7B1 O2 CES2 CYP4B1 NADPH NADP+ 12-HETE CHEBI:63828 ChEBI Q99518 Uniprot 5HIALD MAOA CHEBI:41774 ChEBI P31513 Uniprot CHEBI:16238 ChEBI CYP2B6 Q6QHF9 Uniprot NADPH CHEBI:15422 ChEBI CYP4F2 CHEBI:15846 ChEBI OLMS CHEBI:16027 ChEBI CYP8B1 CHEBI:15343 ChEBI O2 CYP4F22 O2 CYP2A13 NADPH CTL FDX1L NH3 O2 PPi NADP+ VACV PHEN AMP CHEBI:18397 ChEBI DEXT CHEBI:50157 ChEBI H+ CHEBI:17927 ChEBI O2 PGH2 CHEBI:16424 ChEBI O2 3OH-PALM NADP+ CHEBI:17312 ChEBI diketone CH2O NADPH O2 CYP4F2 O2 CHEBI:30322 ChEBI CHEBI:15746 ChEBI CHEBI:18090 ChEBI CHEBI:17148 ChEBI CHEBI:16610 ChEBI CYP4A11 H2O2