Human Gallstones

Prelab Exercise Explain how the process of bromination and debromination of cholesterol can free it from impurities. Write a detailed mechanism for the bromination of cholesterol, taking care to consider the stereochemistry of the product. 

In this experiment cholesterol will be isolated from human gallstones. Cholesterol is an unsaturated alcohol containing 27 carbon atoms and 46 hydrogen atoms  

Cholesterol soluble in methyl tert-butyl ether in the gallbladder 

It is a solid, mp 148.5°C, and is insoluble in water but soluble in boiling ethanol and dioxane. 

HDL high-density lipoproteins (good) LDL low-density lipoproteins (bad) 

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Cholesterol is a solid alcohol the average human body contains about 200 g distributed in brain, spinal cord, and nerve tissue and occasionally clogging the arteries and the gall bladder (see Chapter 22 for background and procedure for isolating cholesterol from human gallstones). 

Many of the experiments are classics introduced by Louis Fieser, for example, the isolation of cholesterol from human gallstones, the use of very high boiling solvents to speed syntheses of such compounds as tetraphenylcyclopentadiene and p-terphenyl, and the Martins Yellow experiment (Chapter 61). 

Cholesterol (C27H46O) (1) is the most widely occurring sterol in all the animal tissues as a constituent of animal membranes. Since it was first isolated from human gallstone, this compound was named cholesterol from the Greek word for bile solids . Cholesterol is synthesized from... 

Sahuquilo R, Rubio JM, Ribo E, Ros and M VELA (2000) Application of focused —microwave wet digestion to the determination of trace metals in human gallstones by ICP/AES. J Trace Elements Med Biol 14 96-99. 

These results raise the question of whether these amorphous stones containing calcium bile salts could be related to the pathogenesis of the cholesterol stones. Glycine-conjugated bile salts, particularly of the less soluble compounds such as chenodeoxycholate and lithocholate, have been found in greater proportions in the centers of human gallstones (167), and it would be of interest to know whether this is the case in the cholesterol stones that frequently coexisted in these animals. 

Cholesterol, one of the most widely occurring steroids, can be isolated by extraction of nearly all animal tissues. Human gallstones are a particularly rich source. 

Human gallstones are almost pure cholesterol this gallstone is about 0.5 cm in diameter. 

Figure 4.38 Dissolution behavior of coprecipitated (A), anhydrous (O), and hydrated ( ) cholesterol and of human gallstone ( ) in a model bile system. From Mufson et al. [272] with permission.

Another experimental approach to gallstone therapy is the use of phenobarbital. In Rhesus monkeys it increases bile salt and phospholipid secretion into bile without significantly changing cholesterol secretion.98 Furthermore, it has been reported to decrease cholesterol saturation in hepatic bile in man.99 Phenobarbital s ability to decrease the relative cholesterol content in bile may allow dissolution of cholesterol gallstones after long-term therapy. Neither lecithin nor cholestyramine are effective in human gallstone disease.100... 

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