Regulation of human arylamine N-acetyltransferase transcription, translation and protein stability

在饮食和工作场所，个人对许多药物和其他化学物质的反应非常不同。这种变异在治疗患者和试图确定暴露于毒素的风险时可能是一个重要的并发症。个体之间的遗传差异是造成这种变异的一个常见原因。然而，人类中的许多酶和其他蛋白质受到环境因素的控制，这些因素既可以增加它们的活性，也可以抑制它们的活性。在这项研究中，我们将研究一个重要的酶家族(乙酰基转移酶)的活性是如何因环境因素而在个体之间发生变化的。我们将研究每种酶的基因，并了解这种控制机制。我们还将仔细研究蛋白质的结构，并确定当受到外部刺激时，这种结构可能会如何变化。预期的结果将是更好地了解这些参与许多药物新陈代谢的重要酶，并提供一种手段，以确定不同的个人可能对外国化学品和药物的反应，这些药物在体内使用这些酶进行新陈代谢。

Individuals respond very differently to many drugs and other chemicals in the diet and workplace. This variation can be a significant complication in treating patients and in attempting to determine risk with exposure to toxins. Genetic differences between individuals are a common reason for this variation. However, many enzymes and other proteins in humans are controlled by environmental factors that can either increase their activity or inhibit it. In this study, we will investigate how the activity of an important family of enzymes (the acetyltransferases) varies between individuals as a result of environmental factors. We will look at the genes for each of the enzymes and learn about this control mechanism. We will also look careful at the structure of the proteins and determine how this may change when challenged with external stimuli. The expected outcome will be a better understanding of these important enzymes that are involved in the metabolism of many drugs, and also provide a means of determining how different individuals may respond to foreign chemicals and drugs that use these enzymes in the body for metabolism.