Effect of natural and structurally modified bile acids on cholesterol metabolizing enzymes in rat liver microsomes. II

✍ Scribed by E. De Fabiani; M. Crestani; L. Fasoli; E. Bosisio

• Publisher: Elsevier Science
• Year: 1991
• Tongue: English
• Weight: 350 KB
• Volume: 57
• Category: Article
• ISSN: 0009-3084
• DOI: 10.1016/0009-3084(91)90054-f

✦ Synopsis

The effect of ursodeoxycholic acid analogues bearing modifications at the side-chain moiety of the molecule was tested on cholesterol 7a-hydroxylase and HMG-CoA reductase in rat liver microsomes. The compounds included 23R,S mixture and the single isomers 23R and 23S of 23 methylursodeoxycholic acid (23-methyl UDCA), the isomeric mixture (cis + trans) of 3a,7Bdibydroxy-20,22-methylen-5B-cholan-23-oic acid (norcypro-UDCA) and the corresponding single isomers. Each steroid was added to liver microsomes as the sodium salt, at concentrations ranging from 25 to 200 ~M. Isomers 23R and 23S of 23-methyl-UDCA inhibited cholesterol 7a-hydroxylase in a concentration-dependent manner. The inhibitory capacity was similar for the two isomers. The extent of inhibition oftbe analogues was greater than that of the parent compound UDCA. Shortening of the side-chain in norcypro-UDCA resulted in a partial loss of the inhibitory effect, as compared to cypro-UDCA (3a,7B-dibydroxy-22,23-methylen-5B-cholan-24-oic acid). None of these bile acid derivatives affected the activity of the enzyme HMG-CoA reductase.