Naslov
Oxidation of Salicylic Acid and Aspirin by Human Cytochromes P450

Autori
Sedgeman, Carl A. ; Bojić, Mirza ; Guengerich, F. Peter.

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Izvornik
2015 VICB Student Research Symposium ; Oral & Poster Presentations Abstracts / - , 2015

Skup
2015 VICB Student Research Symposium

Mjesto i datum
Nashville (TN), Sjedinjene Američke Države, 13.08.2015

Vrsta sudjelovanja
Poster

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
aspirin; P450

Sažetak
Aspirin (acetylsalicylic acid) is a commonly used analgesic. It is rapidly deacetylated both enzymatically and non-enzymatically to salicylic acid. Salicylic acid can then be further metabolized by conjugation with glycine or glucuronides or by hydroxylation to form 2, 3-dihydroxybenzoic acid (2, 3-DHBA) and 2, 5-dihydroxybenzoic acid (2, 5-DHBA). This oxidation has been suspected to occur from oxygen radicals via Fenton reactions as well as by cytochrome P450 enzymes. We analyzed the formation of 2, 3-DHBA and 2, 5-DHBA in the presence of human liver microsomes by HPLC with fluorescence detection. We were able to determine that microsomal oxidation was much faster for salicylic acid than aspirin. 2, 3-DHBA was found to be the major oxidative product formed from salicylic acid, whereas aspirin could detect only 2, 5-DHBA. Recombinant human P450s 2C8, 2C9, 2C19, 2D6, 2E1, and 3A4 all catalyzed the 5-hydroxylation of salicylic acid. Inhibitor studies were able to confirm that all six of these enzymes played a role in the formation of 2, 3- and 2, 5-DHBA, as well as found that 2A6 and 2B6 played a role in the hydroxylation to 2, 5-DHBA. It was also shown in the inhibitor studies that P450 2E1 was the major enzyme contributing to the in both 3- and 5-hydroxylations.

Izvorni jezik
Engleski

Znanstvena područja
Kemija, Farmacija

POVEZANOST RADA