Structure, function and regulation of human cytosolic sulfotransferases

点击翻译按钮获取中文摘要

The sulfotransferase family of enzymes serve an important role in the metabolism of drugs and foreign chemicals. They also metabolise a range of chemicals that are normally present in the body such as hormones and substances that are involved in brain function (neurotransmitters). Observations from clinical studies suggest that differences in sulfotransferases activities may be a causal factor in the incidence of certain types of cancer and neurodegenerative diseases. Recent advances in understanding the molecular biology of these enzymes have shown us that multiple forms of sulfotransferase existed within the body. In this area my laboratory has been at the forefront of the cloning and characterisation of these enzymes. Indeed, we were the first laboratory to clone the major human sulfotransferase (SULT1A3) responsible for the metabolism of brain neurotransmitters. We have also used new technology to determine the shape of this important enzyme. At the time of writing my laboratory has characterised a total seven human sulfotransferases but unlike SULT1A3, our knowledge of the functional significance of the other six sulfotransferase is poorly understood. Further, our knowledge of what regulates the amount of sulfotransferase in different tissues is practically nonexistent. The thrust of this project is to extend our studies on the physiological function of these enzymes and also through the use of molecular biology techniques understand what controls the level of their expression in different human tissues. This knowledge will provide a basis for understanding the role of sulfotransferases play in drug and chemical metabolism. It will also aid our understanding of their role in hormone and neurotransmitter metabolism and help determine whether they are involved in such diseases as cancer and neurodegenerative diseases.