The biophysical and spectroscopic characterisation of two novel P450 fusion enzymes is reported. The first of these is CYP102A3, which is a fusion of P450 haem and cytochrome P450 reductase (CPR)-like domains and functions as a catalytically self-sufficient fatty acid hydroxylase in its host organism Bacillus subtilis. The elucidation of structural...
Published in Comprehensive Toxicology
Toxicology, simply defined, is the ‘study of poisons’. Fundamental to the discipline of toxicology is the development of experimental approaches that allow for characterization of the broad array of adverse effects that may result from exposure to toxic substances (‘poisons’). Toxic substances occur in many forms, including both natural and man-mad...
Published in Comprehensive Toxicology
Major enzyme systems involved in the biotransformation of xenobiotics via hepatic oxidative (phase I) and conjugative (phase II) pathways are reviewed in the context of physiological and anatomical features that influence these pathways in the intact liver in vivo. Enzyme systems belonging to the phase I category discussed in this chapter include m...
Published in Biochemical and Biophysical Research Communications
Induction of the major drug metabolizing enzyme CYP3A4 by xenobiotics contributes to the pronounced interindividual variability of its expression and often results in clinically relevant drug–drug interactions. It is mainly mediated by PXR, which regulates CYP3A4 expression by binding to several specific elements in the 5′ upstream regulatory regio...
All sea turtle populations face the risk of extinction. Of the threats to sea turtles, the effects of environmental chemicals are the least understood. Polychlorinated biphenyls (PCBs) are toxic, persistent, ubiquitous, anthropogenic halogenated organic contaminants (HOCs). While anthropogenic HOCs are notorious for their toxicity, exposure to natu...
All sea turtle populations face the risk of extinction. Of the threats to sea turtles, the effects of environmental chemicals are the least understood. Polychlorinated biphenyls (PCBs) are toxic, persistent, ubiquitous, anthropogenic halogenated organic contaminants (HOCs). While anthropogenic HOCs are notorious for their toxicity, exposure to natu...
Published in Biochemical and Biophysical Research Communications
Fungi, particularly the white rot basidiomycetes, have an extraordinary capability to degrade and/or mineralize (to CO 2) the recalcitrant fused-ring high molecular weight (⩾4 aromatic-rings) polycyclic aromatic hydrocarbons (HMW PAHs). Despite over 30 years of research demonstrating involvement of P450 monooxygenation reactions in fungal metabolis...
Published in Comprehensive Toxicology
Chemicals that cause loss of ovarian follicles are of toxicological importance because females are born with a finite number of primordial follicles. Premature loss of this follicle pool can accelerate the time to ovarian senescence or menopause in women, ultimately reducing the reproductive life span. Many, but by no means all, xenobiotics require...
Published in Comprehensive Toxicology
Alcoholic liver disease (ALD) remains a major cause of morbidity and mortality worldwide. For example, the Veterans Administration Cooperative Studies reported that patients with cirrhosis and superimposed alcoholic hepatitis had a 4-year mortality of >60%. The poor prognosis of ALD implies that preventing disease progression would be more effectiv...
Published in Comprehensive Toxicology
The health, economic, and sociologic benefits of breastfeeding are substantial. As a result, women are encouraged to exclusively breastfeed their infants until they are around six months of age. However, the transfer of drugs and other xenobiotics to the infant via breast milk is a frequent cause of concern. Many women requiring drug therapy interr...
