Premium
Inhibition of cholesterol synthesis by β‐benzal butyric acid and derivatives
Author(s) -
Porcellati G.,
Giorgini D.,
Toja E.
Publication year - 1969
Publication title -
lipids
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.601
H-Index - 120
eISSN - 1558-9307
pISSN - 0024-4201
DOI - 10.1007/bf02532628
Subject(s) - lanosterol , butyric acid , squalene , chemistry , cholesterol , biochemistry , biosynthesis , mevalonic acid , acetic acid , enzyme , metabolite , specific activity , in vitro , stereochemistry , sterol
Cholesterol biosynthesis has been examined using rat liver slices in vitro from 2‐ 14 C‐acetate and 2‐ 14 C‐mevalonate, in the presence of β‐benzal butyric acid (BBA) and its metabolite, α‐hydroxy β‐benzal butyric acid (HBBA), both of which are postulated to act as potential hypocholesterolemic agents. Procedures have been devised to follow radioactivity incorporation of these precursors into the squalene, lanosterol and cholesterol fractions. The results show that cholesterol synthesis from labeled acetate is noticeably inhibited by BBA final concentrations as small as 10 μM, while the rate of labeling is much less inhibited by HBBA. When acetate is replaced by labeled mevalonate, cholesterol synthesis is hardly inhibited by both BBA and HBBA. The results indicate that BBA probably affects some of the reactions which lead acetate to mevalonate formation. Acetyl‐CoA: ligase (E.C.6.2.1.1) and acetyl‐CoA acetyl transferase (E.C.2.3.1.) therefore have been examined. Ligase activity is substantially inhibited only by 1 mM concentration of BBA and HBBA, whereas the transferase enzyme is unaffected. BBA probably affects other reactions in the metabolic sequence which converts acetate into mevalonate.