Cholesterol from human gallstones

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). 

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

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... 

Lithocholic acid was first isolated from a gallstone by Fischer in 1911 (30). It was later isolated from ox bile (1 g from 100 kg of bile) (64) from rabbit bile (0.4 g from 900 ml) (65) and subsequently from monkey, human, pig, and guinea pig bile (2, 66, 67). Lithocholic acid has been identified as one of the bile acids in human blood (68) and as a principal fecal bile acid. Moset-tig et al. (69) isolated lithocholic acid from human stool and estimated its concentration to be 3 g/100 kg of fresh stool. Lithocholic acid is particularly insoluble, is not hydroxylated to an appreciable extent in man (70), and may be the cause of liver disease (4). In early studies lithocholic acid was not available in sufficient amounts from natural sources and was prepared from cholic acid. Lithocholic acid was particularly valuable in establishing the correspondence of the B/C ring structure between bile acids and cholesterol (71). 

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.

Two nucleation processes important to many people (including some surface scientists ) occur in the formation of gallstones in human bile and kidney stones in urine. Cholesterol crystallization in bile causes the formation of gallstones. Cryotransmission microscopy (Chapter VIII) studies of human bile reveal vesicles, micelles, and potential early crystallites indicating that the cholesterol crystallization in bile is not cooperative and the true nucleation time may be much shorter than that found by standard clinical analysis by light microscopy [75]. Kidney stones often form from crystals of calcium oxalates in urine. Inhibitors can prevent nucleation and influence the solid phase and intercrystallite interactions [76, 77]. Citrate, for example, is an important physiological inhibitor to the formation of calcium renal stones. Electrokinetic studies (see Section V-6) have shown the effect of various inhibitors on the surface potential and colloidal stability of micrometer-sized dispersions of calcium oxalate crystals formed in synthetic urine [78, 79]. 

Cholesterol is the central compound m any discussion of steroids Its name is a combination of the Greek words for bile (chole) and solid (stereos) preceding the characteristic alcohol suffix ol It is the most abundant steroid present m humans and the most important one as well because all other steroids arise from it An average adult has over 200 g of cholesterol it is found m almost all body tissues with relatively large amounts present m the brain and spinal cord and m gallstones Cholesterol is the chief constituent of the plaque that builds up on the walls of arteries m atherosclerosis... 

Cholesterol is a vital component of the human body. It stabilizes cell membranes and is the precursor of bile acids, vitamin D, and steroid hormones. The body s cells can synthesize cholesterol when needed, but excess cholesterol cannot be broken down and must be excreted from the body through the bile into the small intestine. When imbalances occur, cholesterol can accumulate in the gallbladder promoting gallstone formation. Cholesterol accumulation in the bloodstream (hypercholesterolemia) can cause atherosclerotic plaques to form within artery walls. 

In addition to the mouse CYP7A1 knockouts, work has been done with overexpression in mice . The mice did not exhibit altered cholesterol levels . The lack of an LXR element in a region (—56 to —49) of the human promoter may dictate some of the differences seen in mouse and human models. With regard to humans, one study of biopsy samples from gallstone patients led to the conclusion that there was no correlation between levels of total bile acids and P450 7A1 activity . A correlation was seen with levels of chenodeoxycholic acid. 

Isolated for the first time in 1775 from gallstones by the physician Benjamin Gottlob Friedrich Conradi (Jena, Germany), cholesterol occurs everywhere in the human body. With high levels especially in the brain, the spinal cord and the suprarenal glands, the total amount of cholesterol in an adult adds up to some 240 grams. Invertebrates, on the other hand, synthesise in addition 24-dehydro-cholesterol in considerable quantity. 

Cholesterol crystallisation is thought to be the first step in the formation of gallstones in the human biliary system and the process of cholesterol nucleation remains incompletely understood. GIXD revealed a phase transition from a monolayer to a highly crystalline rectangular bilayer phase (165). The presence of the phospholipid DPPC in the cholesterol film inhibited cholesterol crystallisation [165]. AFM provided complementary information on the thickness and morphology of the cholesterol films transferred to a solid support The cholesterol monolayer thickness was 13 2 A and in the bilayer phase the presence of elongated faceted crystallites of pure cholesterol about 10 layers thick could be observed [165]. 

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