Genetic Regulation

Humans are exposed continuously and unavoidably to a myriad of potentially toxic chemicals that are inherently lipophilic and, consequently, very difficult to excrete. To effect their elimination, the human body has developed appropriate enzyme systems that can transform metabolically these chemicals to hydrophilic, readily excretable, metabolites. This biotransformation process occurs in two distinct phases. Phase I and Phase II, and involves several enzyme systems, the most important being the cytochromes P450. The expression of these enzyme systems is regulated genetically but can be modulated also other factors, such as exposure to chemicals that can either increase or impair activity. Paradoxically, the same xenobiotic-metabolizing enzyme systems also can convert biologically inactive chemicals to highly reactive intermediates that interact with vital cellular macromolecules and elicit various forms of toxicity. Thus, xenobiotic metabolism does not always lead to deactivation but can result also in metabolic activation with deleterious consequences. 

The exact cause of inflammatory bowel disease (IBD) is unknown, although there are components that appear to be infectious and other components that suggest immune dys-regulation. Genetic variations explain some of the increased risk of disease occurrence. 

BUTCHKO, R.A.E., ADAMS, T.H., KELLER, N.P., Aspergillus nidulans mutants defective in stc gene cluster regulation, Genetics, 1999,153,715-720. 

Regulation, Genetics, and Properties of Adenylosuccinate Synthetase A Review... 

Each of the 57 human P450 genes/gene products will be covered here. Clearly much more information is available about some than others. Points to be covered with each, when possible, include sites of expression and relative abimdance, regulation, genetic variation, substrates and reactions, stracture, inhibitors, and clinical issues. It must be emphasized that this chapter is not intended to be comprehensive, and the literature accumulates rapidly the reader is encouraged to do further literature searches for each P450 of interest. 

Xu M, Ju W, Hao H, Wang G, Li P (2013) Cytochrome P450 2J2 distribution, function, regulation, genetic polymorphisms and clinical significance. Drug Metab Rev 45 311 352... 

Nucleic acids are biological macromolecules that carry important genetic material, and play an essential role in encoding, transmitting, expressing, and regulating genetic information. 

Generator EPA term for any person, organization, or agency whose act or process produces medical waste or causes waste to become subject to regulation Genetic effects hereditary effects (mutations) that can be passed on through reproduction because of changes in sperm or ova... 

Microvesicles shed from the cell, such as exomes, export the miRNAs and transport them to other locations, in effect constituting the intercellular communication and thereby regulating genetic function and protein... 

De Sanctis GT, et al. T-lymphocytes regulate genetically determined airway hyperresponsiveness in mice [see comments]. Nat Med 1997 3(4) 460-462. 

---