Relationship between changes in free cholesterol and pyrophosphomevalonate decarboxylase activity during myelination.

The patterns of cholesterol content in chick brain and liver were studied during embryonic development and compared with the variations in the specific activities of mevalonate-activating enzymes during the same period. Total cholesterol content in both embryonic chick brain and liver increased during incubation. The relative percentage of free cholesterol was always maintained over 85% in brain, while in liver this percentage decreased to less than 10% during the later days of incubation. A straight parallelism was observed between free cholesterol and pyrophosphomevalonate decarboxylase activity in the embryonic brain. On the other hand, the hepatic decarboxylase exhibited a lower specific activity than in brain and did not show significant variations throughout the same period of incubation. Changes in brain pyrophosphomevalonate decarboxylase activity were more pronounced than those observed in both mevalonate kinase and phosphomevalonate kinase activities, in spite of that the specific activity of decarboxylase was the lowest of the three mevalonate-activating enzymes, suggesting that this reaction is one rate-limiting step for cholesterogenesis during myelination.