Persistence of Cholesterol-4-¹⁴C in the Central Nervous System

Abstract

RECENT work from this laboratory^1,2 has shown that once cholesterol-4-¹⁴C is incorporated into the central nervous system of developing rabbits and chickens it remains with little change for more than a year. It seems likely that this radioactive cholesterol is incorporated into the myelin sheath, but there remains the possibility that once in the central nervous system the cholesterol undergoes internal turnover, being broken down and resynthesized in situ. This communication presents evidence to show that the radioactive carbon atom, even after 18 months, remains in its original position in the cholesterol molecule. In these experiments cholesterol extracted from the central nervous system with chloroform–methanol (2 : 1) was isolated by fractionation on an alumina column. The cholesterol was converted to cholestenone by an Oppenauer oxidation³. Next the radioactive cholestenone was ozonized and then oxidized with hydrogen peroxide by the method of Turner⁴. The keto-acid (I) obtained as a result of this elimination of a carbon atom at position 4 was purified and recrystallized. The melting point was in agreement with that reported in the literature^4,5. Comparison of the radioactivity of the cholesterol with the radioactivity of the keto-acid (Table 1) shows that almost all the activity disappears on elimination of the 4-C atom. Furthermore, it was found that all the radioactivity in the original crude extract of the central nervous system was due to its content of radioactive cholesterol (Table 1). This latter result also suggests that the cholesterol molecule remains intact in the central nervous system for more than a year, for if the cholesterol-4-¹⁴C had been degraded it would be anticipated that other radioactive lipids would be synthesized from the resultant fragments. These two groups of experiments, therefore, support the view that the cholesterol that persists in the central nervous system remains metabolically inert for more than a year.