Mutual Influence of Human Cytochrome P450 Enzymes and UDP-Glucuronosyltransferases on Their Respective Activities in Recombinant Fission Yeast
Cytochromes P450 (CYPs) and UDP-glucuronosyltransferases (UGTs) are the most important human drug metabolizing enzymes, but their mutual interactions are poorly understood. In this study, we recombinantly co-expressed of each one of the 19 human members of the UGT families 1 and 2 with either CYP2C9...
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MDPI AG
2023-01-01
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| Series: | Biomedicines |
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| Online Access: | https://www.mdpi.com/2227-9059/11/2/281 |
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| author | Sangeeta Shrestha Sharma Shishir Sharma Jie Zhao Matthias Bureik |
| author_facet | Sangeeta Shrestha Sharma Shishir Sharma Jie Zhao Matthias Bureik |
| author_sort | Sangeeta Shrestha Sharma |
| collection | DOAJ |
| description | Cytochromes P450 (CYPs) and UDP-glucuronosyltransferases (UGTs) are the most important human drug metabolizing enzymes, but their mutual interactions are poorly understood. In this study, we recombinantly co-expressed of each one of the 19 human members of the UGT families 1 and 2 with either CYP2C9, CYP2D6, or CYP4Z1 in fission yeast. Using these strains, we monitored a total of 72 interactions: 57 cases where we tested the influence of UGT co-expression on CYP activity and 15 cases of the opposite approach. In the majority of cases (88%), UGT co-expression had a statistically significant (<i>p</i> < 0.05) effect on P450 activity (58% positive and 30% negative). Strong changes were observed in nine cases, including one case with an activity increase by a factor of 23 (CYP2C9 activity in the presence of UGT2A3) but also four cases with a complete loss of activity. When monitoring the effect of CYP co-expression on the activity of five UGTs, activity changes were generally not so pronounced and, if observed, always detrimental. UGT2B7 activity was not influenced by CYP co-expression, while the other UGTs were affected to varying degrees. These data suggest the notion that mutual influence of CYPs and UGTs on each other’s activity is a widespread phenomenon. |
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| institution | Directory Open Access Journal |
| issn | 2227-9059 |
| language | English |
| last_indexed | 2024-03-11T09:07:34Z |
| publishDate | 2023-01-01 |
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| series | Biomedicines |
| spelling | doaj.art-93cbd6954d5f4459806f4512984004d82023-11-16T19:15:52ZengMDPI AGBiomedicines2227-90592023-01-0111228110.3390/biomedicines11020281Mutual Influence of Human Cytochrome P450 Enzymes and UDP-Glucuronosyltransferases on Their Respective Activities in Recombinant Fission YeastSangeeta Shrestha Sharma0Shishir Sharma1Jie Zhao2Matthias Bureik3School of Pharmaceutical Science and Technology, Tianjin University, 92 Weijin Road, Nankai District, Tianjin 300072, ChinaSchool of Pharmaceutical Science and Technology, Tianjin University, 92 Weijin Road, Nankai District, Tianjin 300072, ChinaSchool of Pharmaceutical Science and Technology, Tianjin University, 92 Weijin Road, Nankai District, Tianjin 300072, ChinaSchool of Pharmaceutical Science and Technology, Tianjin University, 92 Weijin Road, Nankai District, Tianjin 300072, ChinaCytochromes P450 (CYPs) and UDP-glucuronosyltransferases (UGTs) are the most important human drug metabolizing enzymes, but their mutual interactions are poorly understood. In this study, we recombinantly co-expressed of each one of the 19 human members of the UGT families 1 and 2 with either CYP2C9, CYP2D6, or CYP4Z1 in fission yeast. Using these strains, we monitored a total of 72 interactions: 57 cases where we tested the influence of UGT co-expression on CYP activity and 15 cases of the opposite approach. In the majority of cases (88%), UGT co-expression had a statistically significant (<i>p</i> < 0.05) effect on P450 activity (58% positive and 30% negative). Strong changes were observed in nine cases, including one case with an activity increase by a factor of 23 (CYP2C9 activity in the presence of UGT2A3) but also four cases with a complete loss of activity. When monitoring the effect of CYP co-expression on the activity of five UGTs, activity changes were generally not so pronounced and, if observed, always detrimental. UGT2B7 activity was not influenced by CYP co-expression, while the other UGTs were affected to varying degrees. These data suggest the notion that mutual influence of CYPs and UGTs on each other’s activity is a widespread phenomenon.https://www.mdpi.com/2227-9059/11/2/281Cytochrome P450UDP-glucuronosyltransferaseCYP2C9CYP2D6CYP4Z1UGT2B7 |
| spellingShingle | Sangeeta Shrestha Sharma Shishir Sharma Jie Zhao Matthias Bureik Mutual Influence of Human Cytochrome P450 Enzymes and UDP-Glucuronosyltransferases on Their Respective Activities in Recombinant Fission Yeast Biomedicines Cytochrome P450 UDP-glucuronosyltransferase CYP2C9 CYP2D6 CYP4Z1 UGT2B7 |
| title | Mutual Influence of Human Cytochrome P450 Enzymes and UDP-Glucuronosyltransferases on Their Respective Activities in Recombinant Fission Yeast |
| title_full | Mutual Influence of Human Cytochrome P450 Enzymes and UDP-Glucuronosyltransferases on Their Respective Activities in Recombinant Fission Yeast |
| title_fullStr | Mutual Influence of Human Cytochrome P450 Enzymes and UDP-Glucuronosyltransferases on Their Respective Activities in Recombinant Fission Yeast |
| title_full_unstemmed | Mutual Influence of Human Cytochrome P450 Enzymes and UDP-Glucuronosyltransferases on Their Respective Activities in Recombinant Fission Yeast |
| title_short | Mutual Influence of Human Cytochrome P450 Enzymes and UDP-Glucuronosyltransferases on Their Respective Activities in Recombinant Fission Yeast |
| title_sort | mutual influence of human cytochrome p450 enzymes and udp glucuronosyltransferases on their respective activities in recombinant fission yeast |
| topic | Cytochrome P450 UDP-glucuronosyltransferase CYP2C9 CYP2D6 CYP4Z1 UGT2B7 |
| url | https://www.mdpi.com/2227-9059/11/2/281 |
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