Lithocholic add

Lithocholic add costs 2 or 3 times more than cholesterol. Thus, although the yields are slightly lower with cholesterol, it is cheaper to use it Furthermore, cholesterol is more widely available and in greater quantities than lithocholic add. These two factors tend to favour the use of cholesterol. Lithocholic add does have the advantages, however, of being more water soluble and is, therefore, more easily supplied to cultures in aqueous media. The costs of recovery of die desired product from the reaction brew are also commercially important. The point we are making in this in-text activity is that in selecting a substrate we need to consider more than simply the conversion effidency and the cost of the substrate. 

A medium containing bile salts such as lithocholic add along with carbohydrates and peptone has been used to isolate gut organisms. One such isolate has been shown to completely degrade the lithocholic add (structure given in Figure 9.1). 

The data shown in Table 9.3 indicate that highest yields of l,4-androstadiene-3,17-dione are obtained using lithocholic add as substrate. However, dtis substrate is not necessarily the one of choice for the commerdal production of l,4-androstadiene-3,17-dione using A. simplex, list factors that could deteimine the choice of substrate. 

Problem 27.8 Lithocholic acid i.s an A-6 cis steroid found in human bile. Draw lithocholic add showing chair conformations as in Figure 27.4, and tell whether the hydroxyl group at C3 is axial or equatorial. 

FIGURE 3.4 Structures of endogenous compounds involved in glucuronidation bile adds, lithocholic add (LA) and hyodeoxycholic acid (HDCA) short chain bile acids, etianic add and isoetianic add, steroid hormones, androsterone, testosterone, estrone, estradiol, estriol. 

B.a. are biosynthesized from cholesterol by 7a-hy-droxylation, reduction of the double bond at podtion S, and epimerization at position 3. The side chain is shortened by -oxidation. Free B.a. can be prepared by alkaline hydrolysis of animal bile. They are used as starting materials for the partial laboratory synthesis of important steroid hormones. See Cholic acid, Deoxychohc acid, Lithocholic add. 

Bile acids are the end products of hepatic cholesterol catabolism and play essential roles in eliminating cholesterol from the body. However, pathophysiological accumulation of bile acids elicits cytotoxicity and can lead to cholestasis in livers. PXR plays a critical role in bile acid detoxification, by regulating bile add biosynthesis, transport and metaboUsm. Stndies in PXR knock out and humanized PXR mice revealed that PXR reduces secondary bile acid lithocholic add (LCA)-induced liver toxidty [77], PXR regulates... 

---