New enzymatic assay for the AKR1C enzymesBeranič, Nataša, 1985- ...The imbalance in expression of the human aldo-keto reductases AKR1C1-AKR1C3 is related to different hormone dependent and independent cancers and some other diseases. The AKR1C1-3 enzymes thus ... represent emerging targets for the development of new drugs. Currently, various enzymatic assays are used in the search for AKR1C inhibitors, and consequently the results of different research groups are not necessarily comparable. During our recent search for AKR1C inhibitors, we found a cyclopentanol derivative (2-(4-chlorobenzylidene)cyclopentanol, CBCP-ol) and its respective cyclopentanone counterpart (2-(4-chlorobenzylidene)cyclopentanone, CBCP-one) that acted as AKR1C substrates. We determined the kinetic parameters K(M), k(cat) and k(cat)/K(M) for oxidation of CBCP-ol and reduction of CBCP-one by AKR1C enzymes in the presence of NAD(+)/NADP(+) and NADH/NADPH, respectively. The catalytic efficiencies for the oxidation of CBCP-ol in the presence of NAD(+) or NADP(+) were in general higher when compared to the catalytic efficiencies for reduction of CBCP-one in the presence of NADH or NADPH. When NADPH was used, as compared to NADH, the reductions of CBCP-one by AKR1C1, AKR1C2 and AKR1C3 were 14-, 51- and 31-fold more efficient, respectively. When comparing to oxidations of the well-known artificial substrates, 1-acenaphthenol and S-tetralol, we observed similar catalytic efficiencies as for CBCP-ol oxidation with NAD(+) and NADP(+). The comparison of CBCP-one reduction with NADPH to reductions of physiological substrates revealed in general higher efficiencies, except for reduction of 9-cis-retinaldehyde by AKR1C3. This NADPH-dependent reduction of CBCP-one was then used to re-evaluate inhibitory potencies of the known inhibitors of the target AKR1C3 and the anti-target AKR1C2, medroxyprogesterone acetate and ursodeoxycholic acid, respectively, showing K(i) constants similar to the reported values.Vir: Enzymology and molecular biology of carbonyl metabolism (Str. 204-209)Vrsta gradiva - prispevek na konferenci ; neleposlovje za odrasleLeto - 2013Jezik - angleškiCOBISS.SI-ID - 30357465
Vnos na polico
Dostop do baze podatkov JCR je dovoljen samo uporabnikom iz Slovenije. Vaš trenutni IP-naslov ni na seznamu dovoljenih za dostop, zato je potrebna avtentikacija z ustreznim računom AAI.
Baze podatkov, v katerih je revija indeksirana
|Ime baze podatkov||Področje||Leto|
Izberite prevzemno mesto:
Gesla v Splošnem geslovniku COBISS
Prosimo, počakajte trenutek.