Costs of molecular adaptation to the chemical exposome: a focus on xenobiotic metabolism pathways.
Philos Trans R Soc Lond B Biol Sci
; 379(1898): 20220510, 2024 Mar 25.
Article
em En
| MEDLINE
| ID: mdl-38310928
ABSTRACT
Organisms adapt to their environment through different pathways. In vertebrates, xenobiotics are detected, metabolized and eliminated through the inducible xenobiotic-metabolizing pathways (XMP) which can also generate reactive toxic intermediates. In this review, we will discuss the impacts of the chemical exposome complexity on the balance between detoxication and side effects. There is a large discrepancy between the limited number of proteins involved in these pathways (few dozens) and the diversity and complexity of the chemical exposome (tens of thousands of chemicals). Several XMP proteins have a low specificity which allows them to bind and/or metabolize a large number of chemicals. This leads to undesired consequences, such as cross-inhibition, inefficient metabolism, release of toxic intermediates, etc. Furthermore, several XMP proteins have endogenous functions that may be disrupted upon exposure to exogenous chemicals. The gut microbiome produces a very large number of metabolites that enter the body and are part of the chemical exposome. It can metabolize xenobiotics and either eliminate them or lead to toxic derivatives. The complex interactions between chemicals of different origins will be illustrated by the diverse roles of the aryl hydrocarbon receptor which binds and transduces the signals of a large number of xenobiotics, microbiome metabolites, dietary chemicals and endogenous compounds. This article is part of the theme issue 'Endocrine responses to environmental variation conceptual approaches and recent developments'.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Microbioma Gastrointestinal
/
Expossoma
Tipo de estudo:
Health_economic_evaluation
Limite:
Animals
Idioma:
En
Revista:
Philos Trans R Soc Lond B Biol Sci
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
França