Physicochemical Properties of Bile Acids

Bile acids are C-24 to C-28 carboxylic acids with a steroid nucleus containing hydroxylic substituents and part or all of the side chain of 5 -cholestane (Fig. 1). The A/B ring junction is cis (Sp hydrogen) in the bile acids of most higher vertebrates, although A/B trans (alio) bile acids (5a hydrogen) occur in lower vertebrates (HIO). Bile acids do not occur in invertebrates. Most unconjugated bile acids have 24 carbon atoms with the basic structure of 5p- 

Bile acids contain hydroxyl groups, which are usually substituted at positions, C-3, C-7, or C-12 of the steroid nucleus. The three major bile acids found in man are 3a,7a,12a-trihydroxy-5P-cholan-24-oic acid 3a,7a-dihydroxy-5p-cholan-24-oic add and 3a,12a-dihydroxy-5p-cholan-24-oic acid. Because of the complexities of steroid nomenclature, bile acids are nearly always referred to by trivial names. 11108, the three major human bile acids are named cholic acid, chenodeoxycholic acid, and deoxycholic acid, respectively, and their chemical structures are shown in Fig. 1. Human bile does, however, contain small amounts of other bile acids, such as lithocholic acid (3a-hydroxy-5P-cholan-24-oic add) and ursodeoxycholic add (3a,7p-dihydroxy-5p-cholan-24-oic acid) (see Fig. 1). 

There is a wide variety in the types of bile acids found in different animal species. Some species have unique bile acids, such as a-muricholic acid (3a,6p,7a-trihydroxy-5p-cholan-24-oic add) and -muridiolic add (3a,6, 7 -trihydroxy- -cholan 24-oic acid) in rats and mice, and hyodeoxycholic acid (3a,6a-dihydroxy-Sp-cholan 24-oic acid) in pigs. Haslewood (H9) has studied the distribution of bile acids in the animal kingdom and has suggested that the C-24 adds, which are common to most advanced animal forms, can be regarded as the present endpoints in the evolution of the chemical structure of bile adds. 

Another type of conjugation occurring with bile acids involves the hydroxyl groups. These may form sulfate esters or conjugates with glucuronic acid, usually at the 3a position. The formation of sul te esters was first demonstrated as a possible bile acid metabolic pathway in man by Palmer and Bolt (P3). These bile acids can be detected as excretion products in the urine (A6). 

It should be pointed out that in this review no distinction is made between the terms bile acid and bile salt. These terms are used interchangeably, although in a strict sense un-ionized forms should be called bile acids, while 

---

Hofmann, A.F., and A. Roda. 1984. Physicochemical properties of bile acids and their relationship to biological properties An overview of the problem. J Lipid Res 25 1477. 

The topic of bile acids has been the subject of a number of general reviews and books (28, 29, 30, 33, 34). Certain reviews have dealt, in part, with physicochemical aspects of the bile salts (35-39) or have mentioned physicochemical properties only briefly (28, 30, 34, 40). A review dealing specifically with the physicochemical properties of bile salts and their relation to physiologic function was published in 1967 (1). This chapter will be limited to a discussion of the physicochemical properties of bile acids and their salts. (For physiologic correlations, see 1, 8, 9, 10, 41, and 197.)... 

---