Lopez Garcia, M. Pilar published the artcileHuman liver cytochromes P-450 expressed in yeast as tools for reactive-metabolite formation studies. Oxidative activation of tienilic acid by cytochromes P-450 2C9 and 2C10, SDS of cas: 40180-04-9, the main research area is oxidative activation tienilic acid cytochrome yeast; Saccharomyces cytochrome P 450 tienilic acid.
Human liver cytochromes P 450 (P 450) 2C9 and 2C10 expressed in yeast reproduce all the metabolic features of the oxidation of tienilic acid (2-aryloxo-thiophene) and its isomer (3-aroylthiophene) by human liver microsomes. Microsomes of yeast expressing either P 450 2C9 or P 450 2C10 catalyze (a) the 5-hydroxylation of tienilic acid by NADPH and O2 (Km = 6 μM, Vmax = 2.5 turnover/min), (b) the activation of tienilic acid and its isomer into electrophilic metabolites which covalently bind to proteins, and (c) the formation of a mercaptoethanol adduct which results from the trapping of the tienilic acid isomer sulfoxide by this thiol. Microsomes of yeast expressing human liver P 450 3A4, 1A1 and 1A2 are unable to catalyze these reactions. There is a striking similarity between the quant. characteristics of the oxidation of tienilic acid (and its isomer) by yeast-expressed P 450 2C9 (or 2C10) and by human liver microsomes: (a) analogous Km values (around 10 μM) for tienilic acid 5-hydroxylation, (b) a strong inhibition of tienilic acid oxidation by human sera containing anti-(liver kidney microsomes type 2) (anti-LKM2) antibodies, and (c) almost identical relative ratios of tienilic acid metabolic activation/5-hydroxylation and of tienilic acid activation/the activation of its isomer with both systems. Rates of oxidation of tienilic acid (and its isomer) by yeast microsomes are 6-8-fold higher than those found in human liver microsomes, which would be in agreement with the previously reported amount of P 450 2C9 in human liver. These results not only suggest the important role of P 450 2C9 in the oxidative metabolism of tienilic acid in human liver, but also indicate that the 5-hydroxylation reaction could be a useful marker for P 450 2C9 activity and underline the interest of human liver P 450s expressed in yeast as tools for studying the formation of reactive metabolites.
European Journal of Biochemistry published new progress about Enzyme kinetics. 40180-04-9 belongs to class benzothiophene, name is 2-(2,3-Dichloro-4-(thiophene-2-carbonyl)phenoxy)acetic acid, and the molecular formula is C13H8Cl2O4S, SDS of cas: 40180-04-9.
Referemce:
Benzothiophene – Wikipedia,
Benzothiophene | C8H6S – PubChem