| Summary: | Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Biochemical Sciences Candidate: Bc. Michaela Zvěřinová Supervisor: prof. Ing. Vladimír Wsól Ph.D. Title of diploma thesis: Characterization of a new human membrane-bound carbonyl reductase Reducing enzymes are involved in the metabolism of eobiotics and xenobiotics. Carbonyl reductases also belong to the group of reducting enzymes. These are grouped into three protein superfamilies, the SDR, AKR or MDR and they can be either soluble cytosolic or membrane-bound to endoplasmatic reticulum, mitochondria and peroxisomes. Recent research has focused mainly on characterization of microsomal carbonyl reducing enzymes. It has been decribed, only one microsomal carbonyl reductase in metabolism of xenobiotics, 11β-hydroxysteroid dehydrogenase 1. There is a discrepancy in metabolism of oracin between human liver microsomes and purified 11β-hydroxysteroid dehydrogenase 1 so an unknown microsomal carbonyl reductase participates in oracin biotransformation. This enzyme was purified. Carbonyl reductases have broad substrate specificity and also metabolize the strongest tobacco smoke carcinogen NNK. These enzymes reduce NNK to NNAL that can be excrected. The aim of this thesis is to optimize the method for determining metabolite NNAL...
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