Alternative splicing within the human cytochrome P450 superfamily with an emphasis on the brain: the convolution continues

Abstract

The human cytochrome P450 (CYP) superfamily of enzymes regulate hepatic phase 1 drug metabolism and subsequently play a significant role in pharmacokinetics, drug discovery and drug development. Alternative splicing of the cytochrome CYP gene transcripts enhances gene diversity and may play a role in transcriptional regulation of certain CYP proteins. Tissue-specific alternative splicing of CYPs is significant for its potential to add greater dimension to differential drug metabolism in hepatic and extrahepatic tissues, such as the brain, and to our understanding of the CYP family. This review provides an overview of tissue-specific splicing patterns, splicing types, regulation and the functional diversities between liver and splice variant CYP proteins and further explores the relevance of tissue-specific alternative splicing of CYPs in the nervous system.

Keywords::

• alternative splicing
• brain CYPs
• cytochrome P450
• drug metabolism

Acknowledgements

The authors acknowledge the support of this work by NIMH collaborative grant MH070054 awarded to HW Strobel and V Ravindranath and The Texas Training and Technology against Trauma and Terrorism 0004268-T5 Project 7 grant from the US Department of Army awarded to HW Strobel.