Homing-in on the origin of biliary steroids

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Abstract
See article on page 700 The raison d’être of bile is to provide a conduit to eliminate excess cholesterol from the organism.1 Biliary secretion accomplishes this function in two ways. The liver secretes unesterified (free) cholesterol molecules into bile and also converts cholesterol molecules into bile acids, which are secreted as water soluble anions (bile salts). Bile salt synthesis from cholesterol compensates for obligatory faecal loss (as acidic sterols) during enterohepatic cycling, and this feedback control is regulated by the efficiency of bile salt return from the intestine. In a healthy human of ideal body weight, de novo synthesis amounts to about 250 mg a day and the bile salt pool, which approximates 3 g, cycles 8 to 12 times a day; therefore, the contribution of bile salt synthesis to biliary secretion is approximately 1%. In contrast to the efficiency of the enterohepatic circulation, 50% of the 1000 mg of cholesterol secreted daily into bile is lost in faeces as bacterial metabolic products (neutral sterols) in faeces, thereby exceeding the loss of cholesterol as acidic sterols by a factor of 2 to 1. Knowledge of the precursor sources and disposition of biliary cholesterol and bile salts is important for its own sake and to provide targets for new drugs because of the high prevalence rates of atherosclerosis and cholesterol gallstones in Western societies. In both animals and humans, the contributions of de novo cholesterol synthesis to biliary cholesterol secretion, as well as bile salt synthesis, are now considered to be of minor quantitative importance, with estimates as low as 10%.2 Clearly, the evidence suggests that biliary cholesterol and bile salt molecules derive principally from preformed cholesterol in plasma lipoproteins.2-4 Now, Hillebrant and colleagues (see page 700) have narrowed the focus and …