Các ion kim loại được yêu cầu cho chức năng cần thiết, nhưng độc hại vượt quá. Metalloproteins đóng vai trò quan trọng về cấu trúc và chức năng trong chuyển hóa tế bào. Cơ chế hằng định nội môi duy trì một sự cân bằng quan trọng để tránh ngộ độc. Cơ chế này phải có khả năng để đối phó với thay đổi nồng độ kim loại trong môi trường của chúng tôi do chế độ ăn uống hoặc các chất gây ô nhiễm môi trường. Duy trì sự cân bằng đòi hỏi phải có quy định cơ. | 16 Genetic Susceptibility to Heavy Metals in the Environment Diane W. Cox and Lara M. Cullen University of Alberta Edmonton Alberta Canada John R. Forbes McGill University Montreal Quebec Canada 1. INTRODUCTION Many metal ions are required for essential functions yet are toxic in excess. Metalloproteins play important structural and functional roles in cell metabolism. Homeostatic mechanisms maintain a critical balance to avoid toxicity. Such mechanisms must be able to respond to changes in metal concentration in our environment due to diet or environmental pollutants. Maintenance of balance requires regulated absorption transport and excretion mechanisms controlled by a number of genes whose products ensure correct transport of metals to specific sites. Each metal is expected to have its own series of transporters. However as we will show in the following pages several metals are highly dependent upon the concentration of other metals. When any gene within the balanced system is nonfunctional the balance can be upset. The specific genes involved in human transport are best known for copper and iron. Both metals are associated with diseases involving metal storage which Copyright 2002 Marcel Dekker Inc. can be affected by excessive metal intake. These two metals have important interactions. Zinc and molybdate in the form of tetrathiomolybdate each have an effect on the transport of copper. Knowledge of the copper transport pathway has increased dramatically in less than a decade and is the major focus of this chapter. Copper and iron are chosen for discussion also because they demonstrate genetic disorders and show environmental consequences. 2. OVERVIEW OF COPPER TRANSPORT IN HUMANS The average daily copper intake is between 1 and 2 mg and approximately half of this is absorbed 1 . This copper plays an essential role in a number of proteins. Cytochrome oxidase is an inner-membrane mitochondrial protein complex functioning as a key enzyme that catalyzes the .
