Comparing the oxidative functions of neutrophil myeloperoxidase and cytochrome P450 enzymes in drug metabolism
Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved..
Drug metabolism is an essential process that chemically alters xenobiotic substrates to activate or terminate drug activity. Myeloperoxidase (MPO) is a neutrophil-derived haem-containing enzyme that is involved in killing invading pathogens, although consequentially, this same oxidative activity can produce metabolites that damage host tissue and play a role in various human pathologies. Cytochrome P450s (CYPs) are a superfamily of haem-containing enzymes that are significantly involved in the metabolism of drugs by functioning as monooxygenases and can be induced or inhibited, resulting in significant drug-drug interactions that lead to unanticipated adverse drug reactions. In this review, the functions of drug metabolism of MPO and CYPs are explored, along with their involvement and association for common enzymatic pathways by certain xenobiotics. MPO and CYPs metabolize numerous xenobiotics, although few reported studies have made a direct comparison between both enzymes. Additionally, we employed molecular docking to compare the active site and haem prosthetic group of MPO and CYPs, supporting their similar catalytic activities. Furthermore, we performed LCMS analysis and observed a shared hydroxylated mefenamic acid metabolite produced in both enzymatic systems. A proper understanding of the enzymology and mechanisms of action of MPO and CYPs is of significant importance when enhancing the beneficial functions of drugs in health and diminishing their damaging effects on diseases. Therefore, awareness of drugs and xenobiotic substrates involved in MPO and CYPs metabolism pathways will add to the knowledge base to foresee and prevent potential drug interactions and adverse events.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2024 |
|---|---|
| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:392 |
|---|---|
| Enthalten in: |
Chemico-biological interactions - 392(2024) vom: 01. März, Seite 110942 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Tran, Newton H [VerfasserIn] |
|---|
| Links: |
|---|
| Themen: |
42VZT0U6YR |
|---|
| Anmerkungen: |
Date Completed 25.03.2024 Date Revised 26.03.2024 published: Print-Electronic Citation Status MEDLINE |
|---|
| doi: |
10.1016/j.cbi.2024.110942 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM369480406 |
|---|
| LEADER | 01000caa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM369480406 | ||
| 003 | DE-627 | ||
| 005 | 20240326235749.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 240309s2024 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1016/j.cbi.2024.110942 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1349.xml |
| 035 | |a (DE-627)NLM369480406 | ||
| 035 | |a (NLM)38458309 | ||
| 035 | |a (PII)S0009-2797(24)00088-7 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Tran, Newton H |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Comparing the oxidative functions of neutrophil myeloperoxidase and cytochrome P450 enzymes in drug metabolism |
| 264 | 1 | |c 2024 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 25.03.2024 | ||
| 500 | |a Date Revised 26.03.2024 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved. | ||
| 520 | |a Drug metabolism is an essential process that chemically alters xenobiotic substrates to activate or terminate drug activity. Myeloperoxidase (MPO) is a neutrophil-derived haem-containing enzyme that is involved in killing invading pathogens, although consequentially, this same oxidative activity can produce metabolites that damage host tissue and play a role in various human pathologies. Cytochrome P450s (CYPs) are a superfamily of haem-containing enzymes that are significantly involved in the metabolism of drugs by functioning as monooxygenases and can be induced or inhibited, resulting in significant drug-drug interactions that lead to unanticipated adverse drug reactions. In this review, the functions of drug metabolism of MPO and CYPs are explored, along with their involvement and association for common enzymatic pathways by certain xenobiotics. MPO and CYPs metabolize numerous xenobiotics, although few reported studies have made a direct comparison between both enzymes. Additionally, we employed molecular docking to compare the active site and haem prosthetic group of MPO and CYPs, supporting their similar catalytic activities. Furthermore, we performed LCMS analysis and observed a shared hydroxylated mefenamic acid metabolite produced in both enzymatic systems. A proper understanding of the enzymology and mechanisms of action of MPO and CYPs is of significant importance when enhancing the beneficial functions of drugs in health and diminishing their damaging effects on diseases. Therefore, awareness of drugs and xenobiotic substrates involved in MPO and CYPs metabolism pathways will add to the knowledge base to foresee and prevent potential drug interactions and adverse events | ||
| 650 | 4 | |a Comparative Study | |
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Review | |
| 650 | 4 | |a Cytochrome P450 | |
| 650 | 4 | |a Drug metabolites | |
| 650 | 4 | |a Free radicals | |
| 650 | 4 | |a H(2)O(2) | |
| 650 | 4 | |a Heme | |
| 650 | 4 | |a Myeloperoxidase | |
| 650 | 7 | |a Cytochrome P-450 Enzyme System |2 NLM | |
| 650 | 7 | |a 9035-51-2 |2 NLM | |
| 650 | 7 | |a Heme |2 NLM | |
| 650 | 7 | |a 42VZT0U6YR |2 NLM | |
| 650 | 7 | |a Peroxidase |2 NLM | |
| 650 | 7 | |a EC 1.11.1.7 |2 NLM | |
| 650 | 7 | |a Xenobiotics |2 NLM | |
| 700 | 1 | |a Mosa, Farag E S |e verfasserin |4 aut | |
| 700 | 1 | |a Barakat, Khaled |e verfasserin |4 aut | |
| 700 | 1 | |a El-Kadi, Ayman O S |e verfasserin |4 aut | |
| 700 | 1 | |a Whittal, Randy |e verfasserin |4 aut | |
| 700 | 1 | |a Siraki, Arno G |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Chemico-biological interactions |d 1969 |g 392(2024) vom: 01. März, Seite 110942 |w (DE-627)NLM000001848 |x 1872-7786 |7 nnns |
| 773 | 1 | 8 | |g volume:392 |g year:2024 |g day:01 |g month:03 |g pages:110942 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1016/j.cbi.2024.110942 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 392 |j 2024 |b 01 |c 03 |h 110942 | ||