Human Membrane-bound Carbonyl Reductases

ABSTRACT Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Biochemical Sciences Candidate Mgr. Hana ŠTAMBERGOVÁ Supervisor prof. Ing. Vladimír WSÓL, Ph.D. Title of Doctoral Thesis Human membrane-bound carbonyl reductases Human membrane bound enzymes involved in the metabolism of carbonyl containing compounds consitute a highly interesting group of enzymes. Despite the great effort of scientists over the world most of them still remain uncharacterized, mainly those from the large short-chain dehydrogenases/reductases superfamily (SDR). At present, 75 SDR members have been indentified in the human genome whereas only 20 % of them is considered to be well characterized. On the other hand 30 % SDRs remain completly uncharacterized. SDR enzymes are involved in the metabolism of steroids, saccharides, retinoids or prostaglandins and therefore play a crucial role in a number of physiological pathways as well as several serious diseases (e.g. hormon dependent cancer, metabolic syndrome, diabetes mellitus). Moreover, SDR proteins contribute to the biotransformation of some xenobiotic compounds. Several SDR enzymes have been identified to be involved in the phase I metabolism of drugs such as doxorubicin, dolasetron, benfluron, metyrapone or ketoprofen, but so far only one..