Abstract

The effect of unsodeoxycholic acid analogues bearing modifications at the side-chain moiety of the molecule was tested on cholesterol 7α-hydroxylase and HMG-CoA reductase in rat liver microsomes. The compounds included 23 R,S mixture and the single isomers 23 R and 23 S of 23 methylursodeoxycholic acid (23-methyl UDCA), the isomeric mixture ( cis + trans) of 3α,7β-dihydroxy-20,22-methylen-5β-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 μM. Isomers 23 R and 23 S of 23-methyl-UDCA inhibited cholesterol 7α-hydroxylase in a concentration-dependent manner. The inhibitory capacity was similar for the two isomers. The extent of inhibition of the 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 (3α,7β-dihydroxy-22,23-methylen-5β-cholan-24-oic acid). None of these bile acid derivatives affected the activity of the enzyme HMG-CoA reductase.

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