Turnover of plasma cholesterol in man

Cholesterol-4-(14)C was injected intravenously into a series of normal men, untreated hyperlipidemic patients, and hyperlipidemic patients being treated with cholestyramine. The specific radioactivity of plasma total cholesterol was measured during the ensuing 10 wk. 16 studies were carried out in 10 subjects. Analysis of the turnover curves of plasma cholesterol revealed that in every study the turnover of plasma cholesterol conformed to a two-pool model. Each turnover curve was analyzed in terms of this model, as expressed by the equation: specific activity = C(A)e(-alphat) + C(B)e(-betat). The parameters which were calculated included the constants C(A), C(B), alpha, and beta; the size of the first pool (M(A)); the rate constants for the total rate of removal of cholesterol from each pool (k(AA) and k(BB)); and the production rate in pool A (PR(A)). In two normal men and five untreated patients the average size of pool A was 25g. The effect of cholestyramine was assessed by comparing the results obtained without therapy with those obtained during therapy in five subjects studied under both conditions. Cholestyramine therapy produced a large increase in PR(A) (from 0.98 to 1.98 g/day) and in the rate of removal of cholesterol from pool A. Cholestyramine did not significantly alter the size of pool A. It is not possible to calculate the size of the total body exchangeable pool of cholesterol from the turnover curve of plasma cholesterol. It is also not possible to calculate the metabolic turnover rate, i.e., the rate of cholesterol degradation and excretion, in the whole body. This parameter can, however, be estimated by assuming that cholesterol is removed from the body only by way of the tissue pools that comprise pool A. Under these conditions the metabolic turnover rate is equal to the production rate in pool A.