Trihydroxycholanic acid

Synonyms Cholalic acid Cholalin Colalin 3,7,12-Trihydroxycholanic acid 3a,7a,12a-Trihydroxy-5-p-cholan-24-oic acid... 

Uses Oil-phase ingred. for dispersing pigments used in pressed powds. ennol-lient, plasticizer, and skin conditioner in cosmetics Trihydrated alumina. See Aluminum hydroxide 1,1,3-Trihydroperfluoro-1-propanol. See 2,2,3,3-Tetrafluoro-l-propanol 3,7,12-Trihydroxycholanic acid 3a,7a,12a-Trihydroxy-5-P-cholan-24-oic acid. See Cholic acid... 

Bile acids have historically received much less attention than other steroids, for example the corticosteroids however, now that useful thertqreutic effects ate being observed from some bile acids, there is fresh interest in Ais area. A strain of Cunninghamella Uakesleeana has been isolated that will 15p-hy-droxylate lithocholic acid (80 equation 26) in 31% yield.Further reaction is possible to give 3a,lip,15p-trihydroxy-5p-cholanic acid (15%), 3a,15p,18a-trihydioxy-5p-cholanic acid (4%) and 3a,lla,15p-trihydroxycholanic acid (9%). Taurolithocholic acid (81 equation 27) can be 7p-hydroxy-lated in virtually quantitative yield by Mortierella ramanniana. ... 

A few other compounds found in bile of specific animal species should be mentioned briefly. Hammarsten (39) isolated a substance from walrus and sea-lion bile that he showed to be a trihydroxy C24 acid. Windaus and Van Schoor (40) showed this to be an a-hydroxy acid, 3,7,23-trihydroxy-cholanic acid. This compound is called jS-phocaecholic acid. Pythocholic acid (C24H40O5) occurs in the bile of the family of snakes that includes boas and pythons (41, 42). The formula 3a,12a,16a-trihydroxycholanic acid has been suggested (43). Ursodeoxycholic acid (44) occurs in bear bile and is apparently 3a,7 -dihydroxycholanic acid. Hyodeoxycholic acid (3a,6a-dihydroxycholanic acid) has been isolated from hog bile. 

Hyocholic acid was isolated from pig bile by Haslewood in 1954 (123, 124). It has not been detected in the bile of other species. Hyocholic acid was characterized by Haslewood (125), Ziegler (126,127) and by Hsia et al. (89) as 3a,6a,7a-trihydroxycholanic acid. The acid may be synthesized by NaBH4 reduction of 3a,6a-dihydroxy-7-ketocholanic acid, which in turn is prepared from chenodeoxycholic acid (89). 

Pythocholic acid has been isolated from several species of snakes of the family Boidae (132). It was characterized as a 3-, 12-, 15- or 16-trihydroxy-cholanic acid by Haslewood and Wootton (132) and Haslewood (133). The assignment of the 16a-hydroxyl group is consistent with optical rotation data (134). The acid takes its name from the python where it is the principal bile acid. Despite its character as a unique trihydroxycholanic acid, pythocholic acid is probably not a primary acid, but rather formed by hydroxylation of deoxycholic acid returning from the gut (135). 

The chromatographic characteristics of these acids suggested that they were trihydroxycholanic acids. The sulfuric acid absorption spectra of these acids determined according to the procedure of Bernstein and Lenhard (29) exhibited three maxima at 309, 368, and 418 m/ . also suggesting the presence of three hydroxyl groups [Hsia et al. (30)]. Results of elemental analyses were in agreement of the empirical formula of C24H40O5, that of a trihydroxycholanic acid. 

The chief bile acids are the taurine and glycine derivates of dwlic add (3a, 7a, 12a-trihydroxycholanic acid), of deoxycholic add (3a, 12a-dihydroxycholanic acid), and of the isomeric chenodeoxycholic add (3a,7a-dihydroxycholanic acid). The bile acids are one of the end products of the metabolism of cholesterol however, over 90% of the amount secreted (20-30 gm per day) is reabsorbed in the intestine and thus stays in the enterohepatic circulation. 

Constrictor and python snakes have a capacity for the formation of pythocholic acid (3a, 12a, 16a-trihydroxycholanic acid) (Fig. 4) from deoxycholic acid in the liver. From an elaborate study with a bile fistula python and labeled cholesterol, Bergstrom et al. (1960a) showed the step-wise hydroxylation of the sterol nucleus to be 7a and then 12a. The 7a-hydroxyl group is lost through dehydration by the action of intestinal microorganisms and the deoxycholic acid subsequently formed is 16a-hydroxylated in the liver to pythocholic acid. 

Hyodeoxycholic acid is not a primary acid though it is the principal constituent of bladder bile of the pig. The acid from which it is derived by bacterial action in the intestine is 3a,6a,7a-trihydroxycholanic (hyocholic) acid (88). 6-Hydroxylated acids were considered unique to the pig until similar acids were identified as minor constituents in rat fistula bile (89). Since that time hyodeoxycholic acid has been reported to occur in rat plasma and liver (90), in rat bile (91), and in rat feces (92, 93). 

The physical chemistry of micellar structure and formation has been reviewed extensively elsewhere[40,45-47], and is only briefly summarized. The concentration at which micellar aggregation of bile salts molecules occurs (critical micellar concentration, CMC) is affected by bile salt structure, pH, temperature and a variety of other factors. Conjugated bile salts have a higher CMC than the unconjugates, and the CMC for trihydroxycholanates (cholic acid) is higher than for the dihydroxy derivatives. Among the latter, deoxy-cholate forms micelles at a lower CMC than does chenodeoxycholate. 

Figure 4.34 In vitro dissolution rates of various cholanic acid derivative-reserpine coprecipitates in ethyl acetate at 37° C. O, lithocholic acid A cholic acid , deoxycholic acid , 5)9-cholanic acid A, 3,12,24-trihydroxycholane , precipitated reserpine only. From Stoll et al. [240] with permission.

It has been shown that bile acid conjugates have a protective effect against proteolytic inactivation of pancreatic cholesterol esterase (Vahouny ei al., 1965, 1967). Complete protection against inactivation was provided by 3a,12a-dihydroxy and 3o ,7a,12a-trihydroxycholanate. The protective effect seems to be due to the formation of a specific bile salt enzyme complex. Phospholipase A, another pancreatic enzyme, is activated by bile acid conjugates (Magee et al., 1962). This enzyme removes a fatty acid moiety from lecithin, giving lysolecithin. This hydrolysis of lecithin is of importance for the intestinal absorption of this phosphatide (Nilsson and Bergstrom, 1967 Nilsson, 1968). 

---