New developments in the regulation of heme metabolism and their implications

Critical Reviews in Toxicology
M D Maines


Various endogenous and exogenous chemicals, such as hormones, drugs, and carcinogens and other environmental pollutants are enzymatically converted to polar metabolites as a result of their oxidative metabolism by the mixed-function oxidase system. This enzyme complex constitutes the major detoxifying system of man and utilizes the hemoprotein--cytochrome P-450--as the terminal oxidase. Recent studies with trace metals have revealed the potent ability of these elements to alter the synthesis and to enhance the degradation of heme moiety of cytochrome P-450. An important consequence of these metal actions is to greatly impair the ability of cells to oxidatively metabolize chemicals because of the heme dependence of this metabolic process. In this report the effects of exposure to trace metals on drug oxidations is reviewed within the framework of metal alterations of heme metabolism, including both its synthesis and degradation, since these newly discovered properties of metals have made it possible to define a major dimension of metal toxicity in terms of a unified cellular mechanism of action.


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Jan 1, 1987·Journal of Toxicology and Environmental Health·P K Srivastava, U K Misra
Dec 17, 2005·Antioxidants & Redox Signaling·Mahin D Maines
Jan 1, 1997·Annual Review of Pharmacology and Toxicology·M D Maines
May 1, 1997·Brain Research. Brain Research Protocols·J F Ewing, M D Maines
Nov 26, 2002·Medical Hypotheses·D C Downey
Apr 1, 1993·International Journal for Parasitology·P SrivastavaV C Pandey
Oct 7, 2003·European Journal of Drug Metabolism and Pharmacokinetics·Ritu AnejaRamesh Chandra
Jan 1, 1990·Comparative Biochemistry and Physiology. B, Comparative Biochemistry·R F AddisonK W Renton
Jan 1, 1988·The International Journal of Biochemistry·N G AbrahamS Shibahara
Jul 21, 2009·The American Journal of Cardiology·Abhijeet DhobleRanjan K Thakur
May 4, 2000·American Journal of Kidney Diseases : the Official Journal of the National Kidney Foundation·K OhtaS Koizumi
Jul 9, 2003·British Journal of Haematology·Abas H LaftahTimothy J Peters
Sep 1, 1986·Biochemical Pharmacology·J C Veltman, M D Maines
Jun 19, 1998·Chemico-biological Interactions·B Can-EkeM Iscan
Apr 16, 1985·Biochemical and Biophysical Research Communications·M K Qato, M D Maines
May 1, 1994·Medical Hypotheses·D C Downey
Nov 15, 1986·Archives of Biochemistry and Biophysics·G M TrakshelM D Maines
Jan 1, 1987·Annals of the New York Academy of Sciences·A Oskarsson, B A Fowler
Jan 1, 1987·Annals of the New York Academy of Sciences·F W Sunderman
Jan 1, 1988·Journal of Biochemical Toxicology·M E CebriánJ W Bridges
Jan 1, 1989·Archives of Biochemistry and Biophysics·R K Kutty, M D Maines
Jul 15, 1988·Biochemical and Biophysical Research Communications·G M Trakshel, M D Maines
Feb 1, 1988·Archives of Biochemistry and Biophysics·G M TrakshelM D Maines
Aug 1, 1991·Archives of Biochemistry and Biophysics·E L SaundersM L Freeman

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