Table 4.
Examples of the metabolic activation of natural products by human cytochrome P450 enzymes
| Natural product | P450 | Category | Reaction | Reference PMED IDs | Reference No. |
|---|---|---|---|---|---|
| Aflatoxin B1 (AFB1) | 2A13 | Mycotoxin, Aspergillus species | Hydroxylation (AFM1 formation) and epoxidation 8,9- (low activity, activation) | 16385575, 30454686, 22743290 | (Deng et al. 2018; He et al. 2006; Yang et al. 2012) |
| AFB1 | 2W1 | Mycotoxin, Aspergillus species | Oxidation, activation | 16379042 | (Brandon et al. 2006) |
| AFB1 | 2B6 | Mycotoxin, Aspergillus species | Epoxidation 8,9- (low activity, activation) | 8597154, 9280407, 11360624 | (Code et al. 1997; Neal 1995; Wu et al. 1997) |
| AFB1 | 2A6 | Mycotoxin, Aspergillus species | Epoxidation, exo-8,9-, activation | 8082563, 1944238, 16385575, 11189750 | (Gonzalez and Gelboin 1994; He et al. 2006; Lewis et al. 1999; Yun et al. 1991) |
| AFB1 | 3A5 | Mycotoxin, Aspergillus species | Epoxidation, exo-C8,9- (activation, a major enzyme at higher concentration), medium Km, medium activity | 9385444, 9730826, 7893152, 16608170, 30454686, 11189750 | (Deng et al. 2018; Gillam et al. 1995; Kamdem et al. 2006; Kim et al. 1997; Lewis et al. 1999; Wang et al. 1998) |
| AFB1 | 2E1 | Mycotoxin, Aspergillus species | Oxidation (weak activation) | 11189750 | (Lewis et al. 1999) |
| AFB1 | 3A4 | Mycotoxin, Aspergillus species | Epoxidation, exo-8,9- (activation), major enzyme, medium Km and activity | 8261428, 7766804, 12079611, 1902334, 9385444, 11782366, 9730826, 11368545, 16608170, 9003190, 30454686, 8975785, 11497333, 1643250, 11189750 | (Deng et al. 2018; Gallagher et al. 1996; Gallagher et al. 1994; Kamdem et al. 2006; Kim et al. 1997; Lewis et al. 1999; Ramsdell et al. 1991; Raney et al. 1992; Shimada and Guengerich 1989; Ueng et al. 1997; Ueng et al. 1995; Van Vleet et al. 2001; Van Vleet et al. 2002a; Van Vleet et al. 2002b; Wang et al. 1998; Xue et al. 2001) |
| AFB1 | 1A2 | Mycotoxin, of Aspergillus species | Epoxidation, exo-8,9- (activation), and endo-8,9- (detoxication), medium Km and activity | 8261428, 7766804, 12079611, 1902334, 11782366, 16385575, 16608170, 30454686, 8975785, 11497333, 11189750 | (Deng et al. 2018; Gallagher et al. 1996; Gallagher et al. 1994; He et al. 2006; Kamdem et al. 2006; Lewis et al. 1999; Ramsdell et al. 1991; Shimada and Guengerich 1989; Ueng et al. 1995; Van Vleet et al. 2001; Van Vleet et al. 2002a; Van Vleet et al. 2002b) |
| AFB1 | 3A7 | Mycotoxin, Aspergillus species | Epoxidation, exo-8,9- (activation, major enzyme at higher concentration), medium Km, medium activity | 30454686 | (Deng et al. 2018) |
| Aflatoxin G1 (AFG1) | 2A13 | Mycotoxin, Aspergillus species | Oxidation, activation | 23907605 | (Zhang et al. 2013) |
| AFG1 | 1A2 | Mycotoxin, Aspergillus species | Oxidation, activation | 11189750 | (Lewis et al. 1999) |
| AFG1 | 3A4 | Mycotoxin, Aspergillus species | Oxidation, activation | 8082563, 8261428, 7766804, 12079611, 1902334, 352361, 12849689, 11189750 | (Buening et al. 1978; Gallagher et al. 1994; Gonzalez and Gelboin 1994; Lewis et al. 1999; Ramsdell et al. 1991; Sabater Vilar et al. 2003; Ueng et al. 1995; Van Vleet et al. 2002a) |
| Aristolochic acid I | 1A1 | Nephrotoxin and carcinogen, from the plant Aristolochia fangchi and other species and several Asarum species | Nitroreduction, reductive activation, N-hydroxyaristolactam formation | 11511187, 15386410, 23701164, 26593908, 24152141, 22086975, 23353840, 26861298 | (Jerabek et al. 2012; Milichovský et al. 2016; Stiborová et al. 2015; Stiborová et al. 2014; Stiborová et al. 2005; Stiborová et al. 2001b; Stiborová et al. 2012a; Stiborová et al. 2013) |
| Aristolochic acid I | 1A2 | Nephrotoxin and carcinogen, from the plant Aristolochia fangchi and other species and several Asarum species | Nitroreduction, reductive activation, N-hydroxyaristolactam (high activity) | 11511187, 15386410, 23701164, 26593908, 24152141, 22086975, 23353840, 26861298 | (Jerabek et al. 2012; Milichovský et al. 2016; Stiborová et al. 2015; Stiborová et al. 2014; Stiborová et al. 2005; Stiborová et al. 2001b; Stiborová et al. 2012a; Stiborová et al. 2013) |
| Aristolochic acid I | 1A1 | Nephrotoxin and carcinogen, from the plant Aristolochia fangchi and other species and several Asarum species | O-Demethylation, detoxication | 26593908, 22086975 | (Stiborová et al. 2015; Stiborová et al. 2012a) |
| Aristolochic acid I | 1A2 | Nephrotoxin and carcinogen, from the plant Aristolochia fangchi and other species and several Asarum species | O-Demethylation, detoxication | 26593908, 22086975 | (Stiborová et al. 2015; Stiborová et al. 2012a) |
| Aristolochic acid I | 2C9 | Nephrotoxin and carcinogen, from the plant Aristolochia fangchi and other species and several Asarum species | O-Demethylation, detoxication | 26593908 | (Stiborová et al. 2015) |
| Aristolochic acid I | 3A4 | Nephrotoxin and carcinogen, from the plant Aristolochia fangchi and other species and several Asarum species | O-Demethylation, detoxication | 26593908 | (Stiborová et al. 2015) |
| Aristolochic acid II | 1A1 | Nephrotoxin and carcinogen, from the plant Aristolochia fangchi and other species and several Asarum species | Nitroreduction, reductive activation | 11511187, 15386410 | (Stiborová et al. 2005; Stiborová et al. 2001b) |
| Aristolochic acid II | 1A2 | Nephrotoxin and carcinogen, from the plant Aristolochia fangchi and other species and several Asarum species | Nitroreduction, reductive activation (high activity) | 11511187, 15386410 | (Stiborová et al. 2005; Stiborová et al. 2001b) |
| Benzophenone | 1A1 | Muscat grape and mango compound, flavoring substance, ultraviolet protection compound | Benzhydrol and 4-hydroxybezophenone formation, activation | 12160905 | (Takemoto et al. 2002) |
| Benzophenone | 1A2 | Muscat grape and mango compound, flavoring substance, ultraviolet protection compound | Benzhydrol and 4-hydroxybezophenone formation, activation | 12160905 | (Takemoto et al. 2002) |
| Benzophenone | 1B1 | Muscat grape and mango compound, flavoring substance, ultraviolet protection compound | Benzhydrol and 4-hydroxybezophenone formation, activation | 12160905 | (Takemoto et al. 2002) |
| Benzophenone | 2A6 | Muscat grape and mango compound, flavoring substance, ultraviolet protection compound | Benzhydrol and 4-hydroxybezophenone formation, activation | 12160905 | (Takemoto et al. 2002) |
| Curcumin | 2D6 | Coloring agent, yellow pigment from Curcuma longa, chemopreventive | O-Demethylation, activation | 12220536 | (Sakano and Kawanishi 2002) |
| Curcumin | 1A1 | Coloring agent, yellow pigment from Curcuma longa, chemopreventive | O-Demethylation, activation | 12220536 | (Sakano and Kawanishi 2002) |
| Curcumin | 1A2 | Coloring agent, yellow pigment from Curcuma longa, chemopreventive | O-Demethylation, activation | 12220536 | (Sakano and Kawanishi 2002) |
| Δ3-Carene | 1A2 | Bicyclic monoterpene | Epoxidation (high Km, medium activity, activation) | 16379671 | (Duisken et al. 2005) |
| Diallyl sulfone | 2E1 | Garlic oil compound, organosulfur | Oxidation (diallyl sulfoxide and diallyl sulfone formation, activation) | 11062148, 16510538, 11238812 | (Black et al. 2006; Forkert et al. 2000; Yang et al. 2001) |
| Ecteinascidin 743, trabectedin (ET-743) | 3A4 | Marine compound, tetrahydroisoquinoline | Oxidation, low Km, major enzyme, activation | 12231541,16162970, 16379042 | (Reid et al. 2002; Brandon et al. 2005; Brandon et al. 2006) |
| Ecteinascidin 743, trabectedin (ET-743) | 2C9 | Marine compound, tetrahydroisoquinoline | Oxidation, activation | 12231541,16162970, 16379042 | (Reid et al. 2002; Brandon et al. 2005; Brandon et al. 2006) |
| Ecteinascidin 743, trabectedin (ET-743) | 2C19 | Marine compound, tetrahydroisoquinoline | Oxidation, activation | 16162970, 16379042 | (Brandon et al. 2005; Brandon et al. 2006) |
| Ecteinascidin 743, trabectedin (ET-743) | 2E1 | Marine compound, tetrahydroisoquinoline | Oxidation, activation | 12231541,16162970, 16379042 | (Reid et al. 2002; Brandon et al. 2005; Brandon et al. 2006) |
| Ecteinascidin 743, trabectedin (ET-743) | 2D6 | Marine compound, tetrahydroisoquinoline | Oxidation, activation | 12231541,16162970, 16379042 | (Reid et al. 2002;Brandon et al. 2005; Brandon et al. 2006) |
| Estragole | 2A6 | Alkenylbenzene | C1´-Hydroxylation (major enzyme, medium Km, medium activity), activation after sulfation | 17407329 | (Jeurissen et al. 2007) |
| Estragole | 2C19 | Alkenylbenzene | C1´-Hydroxylation (minor enzyme, medium Km, medium activity), activation after sulfation | 17407329 | (Jeurissen et al. 2007) |
| Estragole | 1A2 | Alkenylbenzene | C1´-Hydroxylation, activation after sulfation, high Km, medium activity) | 17407329 | (Jeurissen et al. 2007) |
| Estragole | 2D6 | Alkenylbenzene | C1´-Hydroxylation, activation after sulfation, at high concentrations | 17407329 | (Jeurissen et al. 2007) |
| Estragole | 2E1 | Alkenylbenzene | C1´-Hydroxylation, activation after sulfation, at high concentrations | 17407329 | (Jeurissen et al. 2007) |
| Ethanol | 2C19 | Organic solvent | Oxidation (acetaldehyde formation), activation, high Km, high activity | 17084997 | (Hamitouche et al. 2006) |
| Ethanol | 1A1 | Organic solvent | Oxidation (acetaldehyde formation), activation, high Km (~10 mM), high activity | 17084997 | (Hamitouche et al. 2006) |
| Ethanol | 1B1 | Organic solvent | Oxidation (acetaldehyde formation), activation, high Km (~10 mM), high activity | 17084997 | (Hamitouche et al. 2006) |
| Ethanol | 2B6 | Organic solvent | Oxidation (acetaldehyde formation), activation, high Km (~10 mM), high activity; in vivo after long-term treatment or at high doses | 17084997 | (Hamitouche et al. 2006) |
| Ethanol | 2D6 | Organic solvent | Oxidation (acetaldehyde formation), activation, high Km (~10 mM), high activity; in vivo after long-term treatment or at high doses | 17084997 | (Hamitouche et al. 2006) |
| Ethanol | 2C8 | Organic solvent | Oxidation (acetaldehyde formation), activation, high Km (~10 mM), high activity; in vivo after long-term treatment or at high doses | 17084997 | (Hamitouche et al. 2006) |
| Ethanol | 2C9 | Organic solvent | Oxidation (acetaldehyde formation), activation, high Km (~10 mM), high activity; in vivo after long-term treatment or at high doses | 17084997 | (Hamitouche et al. 2006) |
| Ethanol | 2J2 | Organic solvent | Oxidation (acetaldehyde formation), activation, high Km (~10 mM), high activity; in vivo after long-term treatment or at high doses | 17084997 | (Hamitouche et al. 2006) |
| Ethanol | 4A11 | Organic solvent | Oxidation (acetaldehyde formation), activation, high Km (~10 mM), high activity; in vivo after long-term treatment or at high doses | 17084997 | (Hamitouche et al. 2006) |
| Ethanol | 1A2 | Organic solvent | Oxidation (acetaldehyde formation), activation, high Km (~10 mM), high activity; in vivo after long-term treatment or at high doses | 17084997, 10446146, 9368031, 8627510, 9884161 | (Asai et al. 1996; Bell and Guengerich 1997; Bell-Parikh and Guengerich 1999; Hamitouche et al. 2006) |
| Ethanol | 2E1 | Organic solvent | Oxidation (acetaldehyde formation), activation, high Km (~10 mM), high activity; in vivo after long-term treatment or at high doses | 17084997, 8313838, 10446146, 9368031, 8627510, 7687464, 17084997, 9143349, 30362088 | (Asai et al. 1996; Dai et al. 1993; Hamitouche et al. 2006; Guengerich and Avadhani 2018; Yang and Cederbaum 1997) |
| Ethanol | 3A4 | Organic solvent | Oxidation (acetaldehyde formation), activation, high Km (~10 mM), high activity; in vivo after long-term treatment or at high doses | 17084997, 8571359, 10976571, 10446146, 9368031, 8627510, 9884161 | (Asai et al. 1996; Bell and Guengerich 1997; Bell-Parikh and Guengerich 1999; Hamitouche et al. 2006; Novak and Woodcroft 2000; Raucy 1995; Salmela et al. 1998) |
| Ethyl carbamate (urethane) | 2E1 | Carbamic acid derivative, fermentation byproduct | Oxidation to vinyl carbamate epoxide, activation | 1664256, 1912327 | (Guengerich and Kim 1991; Guengerich et al. 1991) |
| 4-Ipomeanol | 1A2 | Pulmonary toxin, alkylating, from Fusarium solani | Oxidation, activation, major enzyme | 1651809, 15892579 | (Baer et al. 2005; Czerwinski et al. 1991) |
| 4-Ipomeanol | 2C19 | Pulmonary toxin, alkylating, from F. solani | Oxidation, activation, major enzyme | 15892579 | (Baer et al. 2005) |
| 4-Ipomeanol | 2D6 | Pulmonary toxin, alkylating, from F. solani | Oxidation, activation | 15892579 | (Baer et al. 2005) |
| 4-Ipomeanol | 2E1 | Pulmonary toxin, alkylating, from F. solani | Oxidation, activation | 15892579 | (Baer et al. 2005) |
| 4-Ipomeanol | 2F1 | Pulmonary toxin, alkylating, from F. solani | Oxidation, activation | 1651809 | (Czerwinski et al. 1991) |
| 4-Ipomeanol | 3A4 | Pulmonary toxin, alkylating, from F. solani | Epoxidation, activation | 14967002, 17584015 | (Alvarez-Diez and Zheng 2004; Kalgutkar et al. 2007) |
| 4-Ipomeanol | 3A4 | Pulmonary toxin, alkylating, from F. solani | Oxidation, activation, minor enzyme | 1651809, 15892579 | (Baer et al. 2005; Czerwinski et al. 1991) |
| 4-Ipomeanol | 4B1 | Pulmonary toxin, alkylating, from F. solani | Oxidation, activation | 1651809, 23748241, 27092941, 30409834 | (Czerwinski et al. 1991; Roellecke et al. 2016; Teitelbaum et al. 2019) |
| 3-Methylindole (skatole) | 1A2 | Pulmonary toxin | Dehydrogenation (3-methyleneindolenine formation, low Km, high activity, high efficiency, activation) | 8558432, 11408359 | (Lanza and Yost 2001; Thornton-Manning et al. 1996) |
| 3-Methylindole (skatole) | 2A6 | Pulmonary toxin | Epoxidation (3-methyloxindole formation, at high concentration, activation) | 8558432, 11408359 | (Lanza and Yost 2001; Thornton-Manning et al. 1996) |
| 3-Methylindole (skatole) | 1A2 | Pulmonary toxin | Epoxidation (3-methyloxindole formation, low Km, high activity, high efficiency, activation) | 8558432, 11408359 | (Lanza and Yost 2001; Thornton-Manning et al. 1996) |
| 3-Methylindole (skatole) | 1B1 | Pulmonary toxin | Epoxidation (3-methyloxindole form., low Km, high activity, high efficiency, activation) | 8558432, 11408359 | (Lanza and Yost 2001; Thornton-Manning et al. 1996) |
| 3-Methylindole (skatole) | 1A1 | Pulmonary toxin | Epoxidation (3-methyloxindole form., low Km, medium activity, high efficiency, activation) | 8558432, 11408359 | (Lanza and Yost 2001; Thornton-Manning et al. 1996) |
| 3-Methylindole (skatole) | 2E1 | Pulmonary toxin | Epoxidation (3-methyloxindole form., low Km, medium activity, high efficiency, activation) | 8558432, 11408359 | (Lanza and Yost 2001; Thornton-Manning et al. 1996) |
| 3-Methylindole (skatole) | 1A2 | Pulmonary toxin | Hydroxylation, C- (indole-3-carbinol formation, low Km, high activity, high efficiency, activation) | 8558432, 11408359 | (Lanza and Yost 2001; Thornton-Manning et al. 1996) |
| 3-Methylindole (skatole) | 1A1 | Pulmonary toxin | Hydroxylation, C- (indole-3-carbinol formation, low Km, medium activity, high efficiency, activation) | 8558432, 11408359 | (Lanza and Yost 2001; Thornton-Manning et al. 1996) |
| 3-Methylindole (skatole) | 1B1 | Pulmonary toxin | Hydroxylation, C- (indole-3-carbinol formation, low Km, medium activity, high efficiency, activation) | 8558432, 11408359 | (Lanza and Yost 2001; Thornton-Manning et al. 1996) |
| 3-Methylindole (skatole) | 2F1 | Pulmonary toxin | Dehydrogenation (desaturation, 3-methyleneindolenine formation, low Km, medium activity, high efficiency and activation) | 8558432, 11408359, 10383923, 17962375 | (Kartha and Yost 2008; Lanza et al. 1999; Lanza and Yost 2001; Thornton-Manning et al. 1996) |
| 3-Methylindole (skatole) | 2F1 | Pulmonary toxin | Dehydrogenation (desaturation, 3-methyleneindolenine formation, high activation) | 8558432, 11408359, 10383923, 17962375, 20795680, 20187624 | (Kartha and Yost 2008; Lanza et al. 1999; Lanza and Yost 2001; Thornton-Manning et al. 1996; Weems et al. 2010; Weems and Yost 2010) |
| 3-Methylindole (skatole) | 1A1 | Pulmonary toxin | Dehydrogenation (desaturation, 3-methyleneindolenine form., low Km, medium activity, high efficiency, activation) | 8558432, 11408359, 20795680, 20187624 | (Lanza and Yost 2001; Thornton-Manning et al. 1996; Weems et al. 2010; Weems and Yost 2010) |
| 3-Methylindole (skatole) | 2A13 | Pulmonary toxin | Dehydrogenation (desaturation, 3-methyleneindolenine formation, activation) | 8558432, 11408359, 20795680, 20187624 | (Lanza and Yost 2001; Thornton-Manning et al. 1996; Weems et al. 2010; Weems and Yost 2010) |
| 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) | 2E1 | Tobacco-specific nitrosamine | Activation | 19156262 | (Krishnan et al. 2009) |
| NNK | 1B1 | Tobacco-specific nitrosamine | Activation (low activation) | 19156262 | (Krishnan et al. 2009) |
| NNK | 2A13 | Tobacco-specific nitrosamine | Hydroxylation, Cα-methylene (keto aldehyde formation), activation, medium Km, medium activity, or high activity | 11016631, 12975327, 15333516, 15528319, 15962925, 12130698 | (Bao et al. 2005; He et al. 2004b; Jalas et al. 2003; Su et al. 2000; Wong et al. 2005b; Zhang et al. 2002) |
| NNK | 2A13 | Tobacco-specific nitrosamine | Hydroxylation, Cα-methyl (keto alcohol), major enzyme for activation, medium Km, medium activity, or high activity | 11016631, 12975327, 15333516, 15528319, 15962925, 12130698, 17671098, 21473878, 23917075 | (Bao et al. 2005; Chiang et al. 2011; He et al. 2004b; Jalas et al. 2003; Megaraj et al. 2014; Su et al. 2000; Wong et al. 2005b; Zhang et al. 2007; Zhang et al. 2002) |
| NNK | 2B6 | Tobacco-specific nitrosamine | Hydroxylation, α-methyl (keto alcohol formation), activation, major reaction | 11360624, 12920169, 16174803, 9280407, 1312898, 8806763, 9106248, 8485585 | (Code et al. 1997; Crespi et al. 1997; Dicke et al. 2005; Patten et al. 1996; Penman et al. 1993; Smith et al. 2003a; Smith et al. 1992; Wu et al. 1997) |
| NNK | 2F1 | Tobacco-specific nitrosamine | Hydroxylation, α-methyl (keto alcohol formation), activation | 1312898, 8806763 | (Patten et al. 1996; Smith et al. 1992) |
| NNK | 2A6 | Tobacco-specific nitrosamine | Hydroxylation, Cα-methyl (keto alcohol and ketoaldehyde formation), high Km, low activity, minor reaction, weak activation | 1312898, 8806763, 1423839, 9106248, 9280407, 8485585, 10837014, 11600130, 12920169, 11016631, 11080669, 14668073, 15333516, 16364922, 21473878 | (Chiang et al. 2011; Code et al. 1997; Crespi et al. 1997; Fujita and Kamataki 2001b; He et al. 2004b; Kushida et al. 2000; Patten et al. 1996; Penman et al. 1993; Sellers et al. 2003; Smith et al. 2003a; Smith et al. 1992; Su et al. 2000; von Weymarn et al. 2006; Yamazaki et al. 1992) |
| NNK | 2E1 | Tobacco-specific nitrosamine | Hydroxylation, Cα-methylene (keto aldehyde formation), high Km, low activity, minor reaction, activation | 1312898, 8806763, 1423839, 9106248, 9280407, 8485585, 10837014, 11600130, 12920169 | (Code et al. 1997; Crespi et al. 1997; Fujita and Kamataki 2001b; Kushida et al. 2000; Patten et al. 1996; Penman et al. 1993; Smith et al. 2003a; Smith et al. 1992; Yamazaki et al. 1992) |
| NNK | 2E1 | Tobacco-specific nitrosamine | Hydroxylation, Cα-methyl (keto alcohol), high Km, medium activity, major reaction, activation | 1312898, 8806763, 1423839, 9106248, 9280407, 8485585, 10837014, 11600130 | (Code et al. 1997; Crespi et al. 1997; Fujita and Kamataki 2001b; Kushida et al. 2000; Patten et al. 1996; Penman et al. 1993; Smith et al. 1992; Yamazaki et al. 1992) |
| NNK | 2D6 | Tobacco-specific nitrosamine | Hydroxylation, Cα-methyl (keto alcohol), high Km, medium activity, or high activity, major reaction, activation | 1312898, 8806763, 9106248, 9280407, 8485585 | (Code et al. 1997; Crespi et al. 1997; Patten et al. 1996; Penman et al. 1993; Smith et al. 1992) |
| NNK | 1A2 | Tobacco-specific nitrosamine | Hydroxylation, α-methyl (keto alcohol formation), high Km, medium activity, activation | 1312898, 8806763, 9106248, 9280407, 8485585, 11774366, 12214673, 16174803, 21473878, 19156262 | (Chiang et al. 2011; Code et al. 1997; Crespi et al. 1997; Dicke et al. 2005; Fujita and Kamataki 2001a; Kamataki et al. 2002; Krishnan et al. 2009; Patten et al. 1996; Penman et al. 1993; Smith et al. 1992) |
| 4-Methylphenol (p-cresol) | 1A1 | Antiseptic, disinfectant | Hydroxylation, C-methyl, 4-hydroxybenzaldehyde formation (activation, low activity) | 16174805 | (Yan et al. 2005) |
| 4-Methylphenol (p-cresol) | 1A2 | Antiseptic, disinfectant | Hydroxylation, C-methyl, 4-hydroxybenzaldehyde formation (activation, high activity) | 16174805 | (Yan et al. 2005) |
| 4-Methylphenol (p-cresol) | 2C19 | Antiseptic, disinfectant | Hydroxylation, C-methyl, 4-hydroxybenzaldehyde formation (activation, low activity) | 16174805 | (Yan et al. 2005) |
| 4-Methylphenol (p-cresol) | 2D6 | Antiseptic, disinfectant | Hydroxylation, C-methyl, 4-hydroxybenzaldehyde formation (activation, low activity) | 16174805 | (Yan et al. 2005) |
| 4-Methylphenol (p-cresol) | 2C9 | Antiseptic, disinfectant | Hydroxylation, C-methyl, 4-hydroxybenzaldehyde formation (activation, low activity) | 16174805 | (Yan et al. 2005) |
| 4-Methylphenol (p-cresol) | 3A4 | Antiseptic, disinfectant | Hydroxylation, C-methyl, 4-hydroxybenzaldehyde formation (activation, low activity) | 16174805 | (Yan et al. 2005) |
| 4-Methylphenol (p-cresol) | 2E1 | Antiseptic, disinfectant | Hydroxylation, C-aromatic, formation of 4-methyl-o-hydroquinone (activation, high activity) | 16174805 | (Yan et al. 2005) |
| 4-Methylphenol (p-cresol) | 2C19 | Antiseptic, disinfectant | Hydroxylation, C-aromatic, formation of 4-methyl-o-hydroquinone (activation, low activity) | 16174805 | (Yan et al. 2005) |
| 4-Methylphenol (p-cresol) | 2C9 | Antiseptic, disinfectant | Hydroxylation, C-aromatic, formation of 4-methyl-o-hydroquinone (activation, low activity) | 16174805 | (Yan et al. 2005) |
| 4-Methylphenol (p-cresol) | 1A1 | Antiseptic, disinfectant | Hydroxylation, C-aromatic, formation of 4-methyl-o-hydroquinone (activation, low activity) | 16174805 | (Yan et al. 2005) |
| 4-Methylphenol (p-cresol) | 1A2 | Antiseptic, disinfectant | Hydroxylation, C-aromatic, formation of 4-methyl-o-hydroquinone (activation, low activity) | 16174805 | (Yan et al. 2005) |
| 4-Methylphenol (p-cresol) | 2D6 | Antiseptic, disinfectant | Hydroxylation, C-aromatic, formation of 4-methyl-o-hydroquinone (activation, low activity) | 16174805 | (Yan et al. 2005) |
| 4-Methylphenol (p-cresol) | 3A4 | Antiseptic, disinfectant | Hydroxylation, C-aromatic (activation, low activity) | 16174805 | (Yan et al. 2005) |
| 4-Methylphenol (p-cresol) | 2E1 | Antiseptic, disinfectant | Hydroxylation, C-methyl, 4-hydroxybenzaldehyde formation (low activity) | 16174805 | (Yan et al. 2005) |
| 3-N-Nitrosoguvacine (NGC) | 1A1 | Nitrosamine, betel quid, Areca nut compound | Oxidation, activation | 23983642 | (Lin et al. 2013) |
| NGC | 2A6 | Nitrosamine, betel quid, Areca nut compound | Oxidation, activation | 23983642 | (Lin et al. 2013) |
| NGC | 2E1 | Nitrosamine, betel quid, Areca nut compound | Oxidation, activation | 23983642 | (Lin et al. 2013) |
| 3-N-Nitrosoguvacoline (NGL) | 2A13 | Nitrosamine, betel quid, Areca nut compound | Oxidation, major enzyme, activation | 15725615 | (Miyazaki et al. 2005) |
| NGL | 2A6 | Nitrosamine, betel quid, Areca nut compound | Oxidation, major enzyme, activation | 15725615, 23983642 | (Lin et al. 2013; Miyazaki et al. 2005) |
| NGL | 2E1 | Nitrosamine, betel quid, Areca nut compound | Oxidation, activation | 23983642 | (Lin et al. 2013) |
| 3-(N-Nitrosomethylamino)propionaldehyde (NMPA) | 1A1 | Nitrosamine, betel quid, Areca nut compound | Oxidation, activation | 15725615, 23983642 | (Lin et al. 2013; Miyazaki et al. 2005) |
| NMPA | 1B1 | Nitrosamine, betel quid, Areca nut compound | Oxidation, activation | 15725615 | (Miyazaki et al. 2005) |
| NMPA | 2A13 | Nitrosamine, betel quid, Areca nut compound | Oxidation, major enzyme, activation | 15725615 | (Miyazaki et al. 2005) |
| NMPA | 2A6 | Nitrosamine, betel quid, Areca nut compound | Oxidation, activation | 15725615, 23983642 | (Lin et al. 2013; Miyazaki et al. 2005) |
| NMPA | 2E1 | Nitrosamine, betel quid, Areca nut compound | Oxidation, activation | 15725615, 23983642 | (Lin et al. 2013; Miyazaki et al. 2005) |
| 3-(N-Nitrosomethylamino)propionitrile (NMPN) | 1B1 | Nitrosamine, betel quid, Areca nut compound | Oxidation, activation | 15725615 | (Miyazaki et al. 2005) |
| NMPN | 2A13 | Nitrosamine, betel quid, Areca nut compound | Oxidation, activation | 15725615 | (Miyazaki et al. 2005) |
| NMPN | 2A6 | Nitrosamine, betel quid, Areca nut compound | Oxidation, major enzyme, activation | 15725615, 23983642 | (Lin et al. 2013; Miyazaki et al. 2005) |
| NMPN | 2E1 | Nitrosamine, Betel quid, Areca nut compound | Oxidation, major enzyme, activation | 15725615, 23983642 | (Lin et al. 2013; Miyazaki et al. 2005) |
| NMPN | 1A1 | Nitrosamine, betel quid, Areca nut compound | Oxidation, major enzyme, activation | 15725615, 23983642 | (Lin et al. 2013; Miyazaki et al. 2005) |
| Menthofuran | 1A2 | Monoterpene, pennyroyal herb and oil compound, pulegone metabolite | Activation | 26969934 | (Lassila et al. 2016) |
| Menthofuran | 3A4 | Monoterpene, pennyroyal herb and oil compound, pulegone metabolite | Activation | 26969934 | (Lassila et al. 2016) |
| Menthofuran | 2B6 | Monoterpene, pennyroyal herb and oil compound, pulegone metabolite | Activation | 26969934 | (Lassila et al. 2016) |
| Menthofuran (R)-(+)- | 2A6 | Monoterpene, pennyroyal herb and oil compound, pulegone metabolite | C2-Hydroxylation, (2-hydroxymethofuran formation), activation | 10220485 | (Khojasteh-Bakht et al. 1999) |
| Menthofuran (R)-(+)- | 1A2 | Monoterpene, pennyroyal herb and oil compound, pulegone metabolite | C2-Hydroxylation, (2-hydroxymethofuran formation), high Km, low activity, activation | 10220485, 26969934 | (Khojasteh-Bakht et al. 1999; Lassila et al. 2016) |
| Menthofuran (R)-(+)- | 2C19 | Monoterpene, pennyroyal herb and oil compound, pulegone metabolite | C2-Hydroxylation, (2-hydroxymethofuran formation), high Km, low activity, activation | 10220485 | (Khojasteh-Bakht et al. 1999) |
| Menthofuran (R)-(+)- | 2E1 | Monoterpene, pennyroyal herb and oil compound, pulegone metabolite | C2-Hydroxylation, (2-hydroxymethofuran formation), medium Km, low activity, activation | 10220485 | (Khojasteh-Bakht et al. 1999) |
| Methyleugenol | 2C19 | Phenylpropene, from Rhizoma acorigraminei | C1´-Hydroxylation, medium activity, high Km, activation, followed by formation of 1´-sulfooxymethyleugenol | 16411663 | (Jeurissen et al. 2006) |
| Methyleugenol | 2D6 | Phenylpropene, from Rhizoma acorigraminei | C1´-Hydroxylation, medium activity, high Km, activation, followed by formation of 1´-sulfooxymethyleugenol | 16411663 | (Jeurissen et al. 2006) |
| Methyleugenol | 2E1 | Phenylpropene, from Rhizoma acorigraminei | C1´-Hydroxylation, medium activity, high Km, activation, followed by formation of 1´-sulfooxymethyleugenol | 16411663, 9328175 | (Gardner et al. 1997; Jeurissen et al. 2006) |
| Methyleugenol | 1A2 | Phenylpropene, from Rhizoma acorigraminei | C1´-Hydroxylation, major enzyme, activation, followed by formation of 1´-sulfooxymethyleugenol | 16411663, 25549870 | (Al-Subeihi et al. 2015; Jeurissen et al. 2006) |
| Methyleugenol | 2C9 | Phenylpropene, from Rhizoma acorigraminei | C1´-Hydroxylation, major enzyme, activation, followed by formation of 1´-sulfooxymethyleugenol | 16411663 | (Jeurissen et al. 2006) |
| Methyleugenol | 2B6 | Phenylpropene, from Rhizoma acorigraminei | Epoxidation, major enzyme, activation, followed by formation of 1-sulfooxymethyleugenol | 25549870 | (Al-Subeihi et al. 2015) |
| Monocrotaline | 3A4 | Pyrrolizidine alkaloid, genotoxic | Pyrrole formation, dehydrogenation, activation | 15649625 | (Wang et al. 2005) |
| N´-Nitrosonornicotine (NNN) | 1A1 | Tobacco-specific nitrosamine | Activation | 11774366 | (Fujita and Kamataki 2001a) |
| NNN | 1A2 | Tobacco-specific nitrosamine | Activation | 11774366 | (Fujita and Kamataki 2001a) |
| NNN | 1B1 | Tobacco-specific nitrosamine | Activation | 11774366 | (Fujita and Kamataki 2001a) |
| NNN | 2A6 | Tobacco-specific nitrosamine | 5´-Hydroxylation (activation, major enzyme) | 11774366, 12214673, 9029045, 9276639, 15651850 | (Fujita and Kamataki 2001a; Kamataki et al. 2002; Patten et al. 1997; Staretz et al. 1997; Wong et al. 2005b) |
| NNN | 2C19 | Tobacco-specific nitrosamine | Activation | 11774366 | (Fujita and Kamataki 2001a) |
| NNN | 3A4 | Tobacco-specific nitrosamine | 2´-Hydroxylation (activation) | 11774366, 9029045, 9276639 | (Fujita and Kamataki 2001a; Patten et al. 1997; Staretz et al. 1997) |
| NNN | 3A5 | Tobacco-specific nitrosamine | Activation | 11774366 | (Fujita and Kamataki 2001a) |
| NNN | 2A13 | Tobacco-specific nitrosamine | 2´-Hydroxylation (activation, major enzyme) | 15651850 | (Wong et al. 2005b) |
| NNN | 2E1 | Tobacco-specific nitrosamine | 5´-Hydroxylation (activation) | 9276639 | (Patten et al. 1997) |
| NNN | 2D6 | Tobacco-specific nitrosamine | 5´-Hydroxylation (activation, major enzyme) | 9276639 | (Patten et al. 1997) |
| Ochratoxin A | 2C9 | Mycotoxin, from Aspergillus ochraceus and Penicillium verrucosum | Oxidation, activation | 10712746 | (El Adlouni et al. 2000) |
| Ochratoxin A | 1A1 | Mycotoxin, from Aspergillus ochraceus and Penicillium verrucosum | Oxidation, activation | 8542584 | (de Groene et al. 1996) |
| Ochratoxin A | 1A2 | Mycotoxin, from Aspergillus ochraceus and Penicillium verrucosum | Oxidation, activation | 8542584, 11189750 | (de Groene et al. 1996; Lewis et al. 1999) |
| Ochratoxin A | 3A4 | Mycotoxin, from Aspergillus ochraceus and Penicillium verrucosum | Oxidation, activation | 8542584, 16139406 | (de Groene et al. 1996; Simarro Doorten et al. 2006) |
| Pulegone (R)-(+)- | 1A2 | Monoterpene, pennyroyal herb and oil compound | Oxidation, menthofuran formation (high Km, medium activity, medium efficiency, activation) | 10220485 | (Khojasteh-Bakht et al. 1999) |
| Pulegone (R)-(+)- | 2C19 | Monoterpene, pennyroyal herb and oil compound | Oxidation, menthofuran formation (medium Km, medium activity, medium efficiency, activation) | 10220485 | (Khojasteh-Bakht et al. 1999) |
| Pulegone (R)-(+)- | 2E1 | Monoterpene, pennyroyal herb and oil compound | Oxidation, menthofuran formation (major enzyme, medium Km, high activity, medium efficiency, activation) | 10220485 | (Khojasteh-Bakht et al. 1999) |
| Retrorsine | 3A4 | Pyrrolizidine alkaloid, genotoxic | Pyrrole formation, activation | 15649625, 25651456, 24799337, 32469285, 19818743 | (Dai et al. 2010; Fashe et al. 2015; Lu et al. 2020; Tu et al. 2014; Wang et al. 2005) |
| Retrorsine | 2C19 | Pyrrolizidine alkaloid, genotoxic | Pyrrole formation, activation | 19818743 | (Dai et al. 2010) |
| Riddelliine | 3A4 | Pyrrolizidine alkaloid, genotoxic | Pyrrole formation, activation dehydrogenation | 15649625, 32798647 | (Li et al. 2020; Wang et al. 2005) |
| Riddelliine | 3A5 | Pyrrolizidine alkaloid, genotoxic | Pyrrolic metabolite formation, dehydrogenation, activation | 32798647 | (Li et al. 2020) |
| Riddelliine | 3A7 | Pyrrolizidine alkaloid, genotoxic | Pyrrolic metabolite formation, dehydrogenation, activation, low activity | 32798647 | (Li et al. 2020) |
| Safrole | 1B1 | Methylenedioxyphenyl, sassafras oil and betel quid component | C1´-Hydroxylation, activation | 15310247 | (Ueng et al. 2004) |
| Safrole | 2A6 | Methylenedioxyphenyl, sassafras oil and betel quid component | C1´-Hydroxylation, major enzyme at low concentration, medium Km, medium activity, activation | 15377158, 15310247, 17407329, 23112005 | (Jeurissen et al. 2004; Jeurissen et al. 2007; Ueng et al. 2004; Uno et al. 2013) |
| Safrole | 2C19 | Methylenedioxyphenyl, sassafras oil and betel quid component | C1´-Hydroxylation, high Km, medium activity, activation | 15377158, 17407329 | (Jeurissen et al. 2004; Jeurissen et al. 2007) |
| Safrole | 2C9 | Methylenedioxyphenyl, sassafras oil and betel quid component | C1´-Hydroxylation, major enzyme at higher conc., high Km, medium activity, activation | 15377158, 15310247, 17407329 | (Jeurissen et al. 2004; Jeurissen et al. 2007; Ueng et al. 2004) |
| Safrole | 3A4 | Methylenedioxyphenyl, sassafras oil and betel quid component | C1´-Hydroxylation, activation | 15310247 | (Ueng et al. 2004) |
| Safrole | 2E1 | Methylenedioxyphenyl, sassafras oil and betel quid component | C1´-Hydroxylation, major enzyme, activation | 15310247, 15377158 | (Jeurissen et al. 2004; Ueng et al. 2004) |
| Safrole | 2D6 | Methylenedioxyphenyl, sassafras oil and betel quid component | C1´-Hydroxylation, activation, high Km, low activity | 15377158 | (Jeurissen et al. 2004) |
| Safrole | 1A2 | Methylenedioxyphenyl, sassafras oil and betel quid component | o-Quinone formation, activation | 30865484, 29082813 | (Hu et al. 2019; Yang et al. 2018) |
| Safrole | 1A1 | Methylenedioxyphenyl, sassafras oil and betel quid component | C1´-Hydroxylation, activation | 15310247 | (Ueng et al. 2004) |
| Senecionine | 3A4 | Pyrrolizidine alkaloid, genotoxic | Pyrrole formation, N-oxygenation, dehydrogenation, activation | 2009596, 8095200 | (Guengerich 1993; Miranda et al. 1991) |
| Sterigmatocystin | 1A1 | Mycotoxin, fungal product | Epoxidation, activation (minor reaction) | 7955101, 20929267, 21913247 | (Cabaret et al. 2011; Cabaret et al. 2010; Shimada et al. 1994) |
| Sterigmatocystin | 1A2 | Mycotoxin, fungal product, xanthon | Epoxidation, activation (minor reaction) | 7955101, 20929267, 21913247 | (Cabaret et al. 2011; Cabaret et al. 2010; Shimada et al. 1994) |
| Sterigmatocystin | 2W1 | Mycotoxin, fungal product | Oxidation, activation | 16551781 | (Wu et al. 2006) |
| Sterigmatocystin | 3A4 | Mycotoxin, fungal product | Epoxidation, activation (minor reaction) | 9328287, 20929267, 21913247, 7554070 | (Cabaret et al. 2011; Cabaret et al. 2010; Gillam et al. 1997; Yamazaki et al. 1995) |
| Sterigmatocystin | 3A7 | Mycotoxin, fungal product | Oxidation, activation | 9328287 | (Gillam et al. 1997) |
| Sterigmatocystin | 1B1 | Mycotoxin, fungal product | Oxidation (weak activation) | 16551781 | (Wu et al. 2006) |
| Sterigmatocystin | 2W1 | Fungal product | Oxidation (activation) | 16379042 | (Brandon et al. 2006) |