Kekki M, Miettinen T A, Wahlström B
J Lipid Res. 1977 Jan;18(1):99-114.
The purpose of the study was to develop a kinetic method for measurement of different parameters of cholesterol metabolism in man using labeled cholesterol precursors that could initially be incorporated even into the slowly exchangeable cholesterol pool. For this purpose, tritiated water and [2-14C]mevalonate were given to five normocholesterolemic subjects and the activities for serum cholesterol and body water were measured serially for up to eight weeks. Elimination of cholesterol was measured by fecal analysis of neutral and acidic steroids. For comparison, two subjects received a mixture of [4-14C]cholesterol and [2-3H]mevalonate. The data were subjected to multicompartmental analysis by computer, with the assumption that synthesis occurred in two compartments. The rapidly exchangeable cholesterol (pool 1) and the fractional hydrogon transport constant from body water to cholesterol could not be measured directly; therefore, the influence of two different mass transport values was tested. The best fit was obtained with the smaller mass of cholesterol in pool 1 associated with a hydrogen transport constant of 0.700 (32 out of 46 hydrogens originate from water). Kinetic analysis of the data allows estimates of the exchangeable cholesterol mass, flux rates of cholesterol between pools 1 and 2, and synthesis of cholesterol separately in the two pools. The results of computer analysis suggested that, in contrast to what has been assumed earlier on the basis of studies with radiolabelled cholesterol, 22-53% of endogenous cholesterol synthesis took place in pool 2 from body water and that this synthesis tended to correlate with the total body fat mass. The study with [2-3H]mevalonate and [4-14C]cholesterol indicated synthesis in pool 2 to be 20-22% of the total. Up to 50% of the DL[2-14C]mevalonate dose was incorporated into cholesterol. The fractional incorporation of DL-mevalonate into pool 2 was correlated with that of tritiated water, indicating that both precursors studied yielded essentially the same kinetic result.
本研究的目的是开发一种动力学方法，用于测量人体胆固醇代谢的不同参数，该方法使用标记的胆固醇前体，这些前体最初可掺入甚至缓慢交换的胆固醇池中。为此，给五名血脂正常的受试者给予了氚水和[2-¹⁴C]甲羟戊酸，并连续测量血清胆固醇和身体水分的活性，长达八周。通过粪便中性和酸性类固醇分析来测量胆固醇的消除情况。为作比较，两名受试者接受了[4-¹⁴C]胆固醇和[2-³H]甲羟戊酸的混合物。数据通过计算机进行多室分析，假设合成发生在两个室中。快速交换的胆固醇（池1）以及从身体水分到胆固醇的氢转运分数常数无法直接测量；因此，测试了两种不同质量转运值的影响。当池1中胆固醇质量较小时，与氢转运常数0.700（46个氢中有32个来自水）相关时，获得了最佳拟合。对数据进行动力学分析，可以估计可交换胆固醇质量、池1和池2之间胆固醇的通量率，以及两个池中胆固醇的合成情况。计算机分析结果表明，与早期基于放射性标记胆固醇研究的假设相反，22%-53%的内源性胆固醇合成发生在池2中，来自身体水分，并且这种合成倾向于与总体脂质量相关。用[2-³H]甲羟戊酸和[4-¹⁴C]胆固醇进行的研究表明，池2中的合成占总量的20%-22%。高达50%的DL[2-¹⁴C]甲羟戊酸剂量掺入了胆固醇中。DL-甲羟戊酸掺入池2的分数与氚水的分数相关，表明所研究的两种前体产生的动力学结果基本相同。
