Indian Institute of Science, Centre for Neuroscience, C.V. Raman Avenue, Bangalore 560012, India.
Expert Opin Drug Metab Toxicol. 2013 May;9(5):551-8. doi: 10.1517/17425255.2013.759208. Epub 2013 Jan 18.
Cytochromes P450 (P450) and associated monooxygenases are a family of heme proteins involved in metabolism of endogenous compounds (arachidonic acid, eicosanoids and prostaglandins) as also xenobiotics including drugs and environmental chemicals. Liver is the major organ involved in P450-mediated metabolism and hepatic enzymes have been characterized. Extrahepatic organs, such as lung, kidney and brain have the capability for biotransformation through P450 enzymes. Brain, including human brain, expresses P450 enzymes that metabolize xenobiotics and endogenous compounds.
An overview of P450-mediated metabolism in brain is presented focusing on distinct differences seen in expression of P450 enzymes, generation of unique P450 enzymes in brain through alternate splicing and their consequences in terms of metabolism of psychoactive drugs and inflammatory prompts, such as leukotrienes, thus modulating inflammatory response.
The brain possesses unique P450s that metabolize drugs and endogenous compounds through pathways that are markedly different from that seen in liver indicating that extrapolation directly from liver to brain is not appropriate. It is therefore necessary to characterize the unique brain P450s and their ability to metabolize xenobiotics and endogenous compounds to better understand the functions of this important class of enzymes in brain, especially human brain.
细胞色素 P450（P450）和相关的单加氧酶是一类血红素蛋白，参与内源性化合物（花生四烯酸、类二十烷酸和前列腺素）以及包括药物和环境化学物质在内的外源性物质的代谢。肝脏是 P450 介导的代谢中主要涉及的器官，已经对其肝酶进行了特征描述。肺、肾和脑等肝外器官具有通过 P450 酶进行生物转化的能力。大脑，包括人脑，表达能够代谢外源性物质和内源性化合物的 P450 酶。
本文重点介绍了脑内 P450 介导的代谢，讨论了 P450 酶表达的明显差异、脑内通过选择性剪接产生独特的 P450 酶，以及它们在代谢精神活性药物和炎症提示物（如白三烯）方面的影响，从而调节炎症反应。
大脑具有独特的 P450 酶，可以通过与肝脏明显不同的途径代谢药物和内源性化合物，这表明不能直接将肝脏的结论外推到大脑。因此，有必要对独特的脑 P450 及其代谢外源性物质和内源性化合物的能力进行特征描述，以更好地了解这一重要酶类在大脑中的功能，特别是在人脑。
