Hyocholic acid

OH-estradiol, 4-OH-estradiol, estrone, dihydrotestosterone, trans-retinoic acid, 4-hydroxy-retinoic acid, hyocholic acid, hyodeoxycholic, testosterone, LTB4... 

The prefixes glyco- and tauro- prevail all others, i.e. glyco-hyocholic acid. F igure 8.11. Structure and nomenclature of bile acids. 

Hydroxy retinoic acid, hyocholic acid, hyodeoxycholic, testosterone, leukotriene B4,... 

TThe following systematic names are given to steroids and bile acids referred to by trivial names cholestanol, 5a-cholestan-3/5-ol cholic acid, 3a,7a,12a-trihydroxy-5j3-cholanoic acid hyocholic acid, 3a,6a,7a-trihydroxy-5/S-cholanoic acid a-muricholic acid, 3a,6/S,7a-trihydroxy-5/S-cholanoic acid /5-muricholic acid, 3a,6/S,7/S-trihydroxy-5/S-cholanoic acid allocholic acid, 3a,7a,12a-trihydroxy-5a-cholanoic acid chenodeoxycholic acid, 3a,7a-dihydroxy-5/5-cholanoic acid deoxycholic acid, 3a,12a-dihydroxy-5iS-cholanoic acid allochenodeoxycholic acid, 3a,7a-dihydroxy-5a-cholanoic acid allodeoxycholic acid, 3a,12a-dihydroxy-5a-cholanoic acid lithocholic acid, 3a-hydroxy-5/5-cholanoic acid. 

The changes of the cholesterol molecule that occur in its conversion into bile acids include epimerization of the 3 -hydroxyl group, reduction of the double bond, introduction of hydroxyl groups in positions C-7 (cheno-deoxycholic acid), C-7 and C-12 (cholic acid), or C-6 and C-7 (a- and P-muricholic acids, hyocholic acid), and transformation of the C27 side chain into a C24-carboxylic acid. 

The bile of germfree swine from two different sources contained the taurine and glycine conjugates of chenodeoxycholic acid, hyodeoxycholic acid, hyocholic acid, and (probably) cholic acid. The hyodeoxycholic acid was present at 4 % by weight and could be detected by TLC as its conjugate. It had previously been felt that hyodeoxycholate in swine was solely a microbial dehydroxylation product of hyocholic acid however, this study shows that it can be biosynthesized by the germfree swine. 

Hydroxyximcnynic acid, in H-00360 Hyocholic acid, in T-00187 Hyodeoxycholic acid, in D-OOl 15 Hyodcoxycholylglycine, in D-OOl 15... 

Figure 13 Chromatograms of gall bladder extracts from the pacific lamprey (A), western brook lamprey (B), and sea lamprey (C). Petromyzonol sulfate (PZS) and allocholic acid (ACA) cleanly separate from each other and hyocholic acid (HA) and lithocholic acid (LCA) are the internal standards. (Reprinted with permission from Steroids, 68 (2003) 515-523 Elsevier.)...

Five bile acids (glyco- and tauro-3a,6a-dihydroxy-5]8-cholanoic acid, cheno-deoxycholic acid, hyocholic acid, 6-ketolitocholic acid) were extracted fix m bile and analyzed as their methyl esters. Baseline resolution was obtained on a cyanopro-pyl column (RI detector) in 25 min when an 89/6/5 hexane/IPA/dichloromethane (+1% 1-pentanol and 1% water) mobile phase was used [687]. 

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). 

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). 

The occurrence of a species-specific bile acid in pig bile [Haslewood (1) Haslewood and Sjovall (2)] and of two such acids in rat bile [Bergstrom and Sjovall (3) Hsia et al. (4) Matschiner et al. (5)] was observed almost simultaneously. After their isolation and characterization, these acids were found to be isomeric 3a,6,7-trihydroxy-5/5-cholanic acids. The acid from pig bile was named hyocholic acid [Haslewood (6) Ziegler (7)], and the two acids from rat bile were named a- and /3-muricholic acids [Hsia et al. (8)]. The fourth isomer of these glycols was identified as a metabolite of hyodeoxycholic acid (3rt,6a-dihydroxy-5 9-cholanic acid) in the rat [Matschiner et al. (9, 10)], and was named ry-muricholic acid [Hsia et al. (8)]. The vicinal glycol structures in ring B of these acids are unique features, but even more unique are their species-specific characteristics which are particularly demonstrated in the metabolic pathways that lead to their formation. 

Haslewood (24) pointed out that hyocholic cannot be separated from hyodeoxycholic acid, another characteristic acid of the pig, by the usual procedures of crystallization. A sample of hyodeoxycholic acid with a sharp melting point of 191-192°C was shown to contain more than 20% of hyocholic acid in his laboratory. Caution therefore must be exercised in interpreting prior data obtained on hyodeoxycholic acid which might have been contaminated with hyocholic acid. 

The structure of hyocholic acid was proposed by Haslewood (24) and by Ziegler (7) to be 3a,6a,7 -trihydroxy-5 -cholanic acid (I, Fig. 1). Since it was known that pig bile contains hyodeoxycholic acid (3a,6a-dihydroxy) and chenodeoxycholic acid (3a,7a-dihydroxy) the bile was assumed to contain possibly also an acid with both 6a- and 7a-hydroxyl groups. Chemical evidence for the vicinal glycol structure in hyocholic acid was found after chromic oxidation. The product, 3-keto-6,7-secocholanic acid-6,7-dioic... 

Fig. 1. Structure of hyocholic acid. [Adapted from Haslewood (24) and Ziegler (7).]...

Hyocholic acid forms an acetonide (IV). Although it could not be crystallized [Ziegler (7) Haslewood (24)], its formation was substantiated by chromatographic mobility and data of quantitative acetylation. Formation of the acetonide gave evidence for the m-glycol structure in hyocholic acid. The a-orientation of this 6,7-glycol was deduced from data of molecular rotations. Based on values from Barton and Klyne (34), the calculated molecular rotation of 3a,6a,7a-trihydroxy-5/3-cholanic acid would be —13 and that of the 3a,6a,7 -isomer, +249. The observed molecular rotation of hyocholic acid was +19. It was therefore concluded that hyocholic acid is the 3a,6a,7a rather than the 3a,6/3,7/3-isomer [Ziegler (7)]. 

Confirmative evidence of the proposed structure was obtained from partial synthesis of hyocholic acid [Hsia et al. (30)]. An important intermediate in the synthesis was 3a,6a-dihydroxy-7-keto-5 -cholanic acid (VII, Fig. 2), first prepared by Takeda et al. (35). The 3 - and 6a-hydroxyl groups in VII were established by the formation of hyodeoxycholic acid (IX) after hydrogenolysis of the ethylenedithioketal derivative (VIII) with Raney nickel. Hyocholic acid was obtained from VII either by reduction with sodium borohydride or by hydrogenation in the presence of platinum both methods were known to produce the axially oriented 7a-hydroxy from 7-keto bile acids [Mosbach et al. (36) Iwasaki (37)]. More direct evidence for the la-hydroxyl group in hyocholic acid was found in a later study [Hsia et al. (8)], when hyocholic acid was derived from bromohydrin acetate XII (Fig. 3),... 

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