Morell P, Jurevics H
Department of Biochemistry and Biophysics University of North Carolina, Chapel Hill 27599-7250, USA.
Neurochem Res. 1996 Apr;21(4):463-70. doi: 10.1007/BF02527711.
We review some of the older literature concerning metabolic turnover of cholesterol in the nervous system. The overall picture is that incorporation of radioactive precursors into brain cholesterol is roughly proportional to the rate of myelination and that, once incorporated, radioactive cholesterol is relatively stable metabolically. We outline a strategy for demonstrating the source (local synthesis or uptake from circulation) of cholesterol in brain. The experimental design involves determining the rate of accumulation of cholesterol; this is calculated as the increasing amounts of sterol in brain at successive time intervals during development. The rate of appearance of newly synthesized cholesterol is determined from incorporation of radioactivity from 3H20 (injected i.p. several hours prior to sacrifice) into cholesterol. The radioactivity associated with the sterol fractions and the specific activity of body water determined from the serum can be used to calculate the absolute amount of sterol newly synthesized during the time when 3H20 was present. The results obtained demonstrated that all of the bulk cholesterol accumulating in brain can be accounted for by newly synthesized cholesterol. None of the radioactive cholesterol came from the circulation, since cholesterol feeding suppressed cholesterol biosynthesis in the liver and specific radioactivity of circulating cholesterol was negligible. Thus, almost all cholesterol accumulating in brain during development is locally synthesized.
我们回顾了一些关于神经系统中胆固醇代谢周转的早期文献。总体情况是，将放射性前体掺入脑胆固醇大致与髓鞘形成速率成正比，并且一旦掺入，放射性胆固醇在代谢上相对稳定。我们概述了一种证明脑中胆固醇来源（局部合成或从循环中摄取）的策略。实验设计包括确定胆固醇的积累速率；这是通过计算发育过程中连续时间间隔内脑中固醇含量的增加量来确定的。新合成胆固醇的出现速率是通过将3H2O（在处死前几小时腹腔注射）的放射性掺入胆固醇来确定的。与固醇部分相关的放射性以及从血清中测定的身体水分的比活性可用于计算在存在3H2O期间新合成的固醇的绝对量。获得的结果表明，脑中积累的所有大量胆固醇都可以由新合成的胆固醇来解释。没有放射性胆固醇来自循环，因为喂食胆固醇会抑制肝脏中的胆固醇生物合成，并且循环胆固醇的比放射性可以忽略不计。因此，发育过程中脑中积累的几乎所有胆固醇都是局部合成的。
