The study of the biological effects of foreign chemicals (whether therapeutic drugs or chemicals present at work or in the environment) interests the biologist from a number of different and complementary viewpoints. Apart from the more obvious pharmacological and toxicological interest, the experimentalist often uses foreign chemicals to produce in experimental animals disease states similar to naturally occurring diseases, so that their pathogenetic mechanisms and therapy can be studied under controlled conditions. In addition - as Claude Bernard pointed out over a century ago - foreign chemicals can be employed as instruments to analyze the most delicate vital processes; much can be learned about the physiological processes themselves by a careful study of the mechanisms by which these are altered by chemicals. The field of heme and hemoproteins offers an example of the interplay of these different approaches. Their metabolism can be altered by therapeutic drugs and other foreign chemicals and this results in a variety of biological responses that transcend the boundaries of pharmacology into the confines of clinical medi cine, genetics, toxicology, biochemistry and physiology. In this book a multidisciplinary approach to the study of heme metabolism is presented including the effect of chemicals on heme metabolism in patients, the results of experimental work in the whole animal, as well as in vitro studies.

Inhalt
1 The Biosynthesis and Degradation of Heme.- A. Introduction.- B. Structures of Porphyrins and Hemes.- C. Function and Turnover of Hemoproteins.- D. Enzymes of Heme Biosynthesis and Degradation.- E. Conjugation of Bilirubin.- F. Control of Heme and Hemoprotein Biosynthesis.- Abbreviations.- References.- 2 Induction of Hepatic Hemoproteins.- A. Introduction.- B. Use of the Term Induction in Studies on Mammalian Tissues.- C. Tryptophan Pyrrolase (Dioxygenase).- D. Cytochromes of the Endoplasmic Reticulum.- E. Catalase.- F. Mitochondrial Cytochromes.- G. Summary of Conclusions.- Recommended Reviews.- References.- 3 Inhibition of Liver Hemoprotein Synthesis.- A. Introduction.- B. Agents Inhibiting Heme Biosynthesis and Hepatic Hemoprotein Synthesis.- C. Conclusions.- Abbreviations.- References.- 4 Loss of Liver Cytochrome P-450 Caused by Chemicals. Damage to the Apoprotein and Degradation of the Heme Moiety.- A. Introduction.- B. Loss of Liver Cytochrome P-450 Caused by Chemicals Which Require Metabolic Conversion to Reactive Derivatives.- C. Increased Breakdown of the Heme of Liver Cytochrome P-450 Associated with Lipid Peroxidation.- D. Loss of Liver Cytochrome P-450 Caused by the Administration of Various Metals.- References.- 5 Hepatic Porphyrias Caused by 2-Allyl-2-isopropylacetamide, 3,5-Diethoxycarbonyl-1,4-dihydrocollidine, Griseofulvin and Related Compounds.- A. Introduction.- B. The Mechanism of Induction of Porphyria by Drugs.- Abbreviations.- References.- 6 Porphyria Caused by Hexachlorobenzene and Other Polyhalogenated Aromatic Hydrocarbons..- A. Introduction.- B. Properties and Metabolism of Porphyrogenic Polyhalogenated Aromatic Hydrocarbons.- C. Porphyria Caused by Hexachlorobenzene and Other Halogenated Aromatic Hydrocarbons.- D. The Effect of Polyhalogenated Aromatic Hydrocarbons on Heme Metabolism in the Liver.- E. The Mechanism of the Porphyrogenic Action of Polyhalogenated Aromatic Hydrocarbons.- F. General Conclusions.- Abbreviations.- References.- 7 The Effect of Chemicals on Hepatic Heme Biosynthesis. Differences in Response to Porphyrin-Inducing Chemicals Between Chick Embryo Liver Cells, the 17-Day-Old Chick Embryo and Other Species..- A. Introduction.- B. Porphyrin Induction in Chick Embryo Liver Cells.- C. Porphyrin Induction in 17-Day-Old Chick Embryos.- D. Porphyrin Induction in Chickens and Japanese Quail.- E. Differences in Response to Porphyrin-Inducing Drugs in Different Species and Model Test Systems.- Abbreviations.- References.- 8 Pharmacogenetics in the Field of Heme Metabolism: Drug Sensitivity in Hereditary Hepatic Porphyria..- A. Hereditary Hepatic Porphyrias.- B. Precipitation of Hereditary Hepatic Porphyria by Drugs.- C. Experimental Models for the Exacerbation of Hereditary Hepatic Porphyria by Drugs.- D. Common Basis for Induction of Hepatic ALA-Synthetase in Clinical and Experimental Porphyria.- References.- 9 The Influence of Hormonal and Nutritional Factors on the Regulation of Liver Heme Biosynthesis..- A. Introduction.- B. The Influence of Nutritional Factors.- C. The Influence of Hormonal Factors.- References.- 10 Effects of Drugs on Bilirubin Metabolism..- Definition of Certain Abnormalities of Bilirubin Metabolism.- A. Introduction.- B. Normal Bilirubin Metabolism.- C. Drug-Mediated Alterations in Bilirubin Metabolism.- References.- 11 Toxic Effects of Lead, with Particular Reference to Porphyrin and Heme Metabolism..- A. Biosynthesis of Heme.- B. Effect of Lead on the Heme Biosynthetic Pathway.- C. Toxic Effects of Exposure to Lead.- D. Biological Defense Mechanisms Against Lead.- E. Factors Affecting the Toxic Effects of Lead.- F. Diagnosis of Lead Poisoning.- G. Summary.- Abbreviations.- References.- Author Index.