Cholesterol Precursor Pools for the Synthesis of Cholic and Chenodeoxycholic Acids in Rats

The rates of excretion and specific activities of total bile acids, cholic acid, chenodeoxycholic acid, and cholesterol excreted in the bile were measured during a diurnal cycle in bile fistula rats fed [3H]cholesterol for 4 to 5 weeks. One [3H]-cholesterol-fed rat received a constant infusion of [2-14C]-mevalonic acid and another received a constant infusion of 7α-hydroxy[4-14C]cholesterol during collection of the bile. The rates of excretion of the four biliary constituents measured exhibited diurnal rhythm, with a maximum during the night and a minimum at noon. The specific activities of total 3H-labeled bile acids and of [3H]cholic acid decreased during the first half of the dark period, to reach a minimum coinciding with the maximum rate of excretion, and then increased during the second half of the dark period. The specific activities of [3H]chenodeoxycholate and [3H]cholesterol did not change appreciably during the diurnal cycle. During [2-14C]mevalonate infusion the specific activity of [14C]cholate varied diurnally in parallel with the change in specific activity of [3H]cholate, but that of [14C]chenodeoxycholate did not change during the diurnal cycle. During 7α-hydroxy[4-14C]cholesterol infusion the specific activity of [14C]cholate varied diurnally in parallel with that of [3H]cholate. The specific activity of [14C]chenodeoxycholate fell markedly during the night and was higher than that of [14C]-cholate throughout the diurnal cycle. These observations indicate that newly synthesized hepatic cholesterol is the preferred substrate for the formation of cholic acid, but they raise the possibility that some chenodeoxycholic acid is formed from a pool of cholesterol other than that from which cholic acid is formed.