Đang chuẩn bị nút TẢI XUỐNG, xin hãy chờ
Tải xuống
Many vertebrate species express two enzymes that are capable of catalysing the reduction of various isomers of biliverdin. Biliverdin-IXa reductase (BVR-A) is most active with its physiological substrate biliverdin-IXa, but can also reduce the three other biliverdin isomers IXb,IXdand IXc. Bili-verdin-IXbreductase (BVR-B) catalyses the reduction of only the IXb,IXd and IXc isomers of biliverdin. | ỊFEBS Journal The use of synthetic linear tetrapyrroles to probe the verdin sites of human biliverdin-IXa reductase and human biliverdin-IXb reductase Edward M. Franklin1 Seamus Browne1 Anne M. Horan1 Katsuhiko Inomata2 Mostafa A. S. Hammam3 Hideki Kinoshita2 Tilman Lamparter4 Georgia Golfis1 and Timothy J. Mantle1 1 Schoolof Biochemistry and Immunology Trinity College Dublin Ireland 2 Division of MaterialSciences Graduate Schoolof NaturalScience and Technology Kanazawa University Ishikawa Japan 3 Department of Chemistry Schoolof Science Nagoya University Aichi Japan 4 Institut fur Botanik I Universitat Karlsruhe TH Germany Keywords Biliverdin dimethyl ester ditaurate inhibitor jaundice tolerance Correspondence E. M. Franklin Schoolof Biochemistry and Immunology Trinity College Dublin Dublin 2 Ireland Fax 353 1677 2400 Tel 353 1896 1612 E-mail efrankli@tcd.ie Received 23 April2009 revised 9 June 2009 accepted 11 June 2009 doi 10.1111 j.1742-4658.2009.07148.x Many vertebrate species express two enzymes that are capable of catalysing the reduction of various isomers of biliverdin. Biliverdin-IXa reductase BVR-A is most active with its physiological substrate biliverdin-IXa but can also reduce the three other biliverdin isomers IXb IXỖ and IXy. Bili-verdin-IXb reductase BVR-B catalyses the reduction of only the IXb IXỖ and IXy isomers of biliverdin. Therefore the activity of BVR-A can be measured using biliverdin-IXa as a specific substrate. We now show that the dimethyl esters of biliverdin-IXb and biliverdin-IXỗ are substrates for BVR-B but not for BVR-A. This provides a useful method for specifically assaying the activity of both BVR-A and BVR-B in crude mixtures using biliverdin-IXa for BVR-A and the dimethyl ester of either biliverdin-IXb or biliverdin-IXỗ for BVR-B. Human BVR-A has been suggested as a pharmacological target for neonatal jaundice. Because of the absence of a crystal structure with biliverdin bound to BVR-A we have investigated indirect ways of .
