Relationship between the pentose-phosphate pathway and the de novo synthesis of fatty acids and cholesterol in oligodendrocyte-enriched glial cultures.

This study focuses on the activity of the pentose-phosphate pathway and its relationship to de novo synthesis of fatty acids and cholesterol in oligodendrocyte-enriched glial cell cultures derived from 1-week old rat brain. The proportion of glucose that was metabolized along the pentose-phosphate pathway was estimated by measuring (14)CO(2) production from [1-(14)C]-, [2-(14)C]- and [6-(14)C]glucose, the utilization of glucose and the production of lactate. Incorporation of (14)C from [(14)C]glucose and from [3-(14)C]acetoacetate into lipids was analysed. The pentose- phosphate pathway produced much more CO(2) from glucose than the Krebs cycle, although it accounted for only a small part of the consumption of glucose (< 3%). The higher (14)CO(2) production from [2-(14)C]glucose than from [6-(14)C]glucose indicated that recycling of the products of the pentose-phosphate pathway takes place in these cells. Gradual inhibition of the pathway with increasing concentrations of 6-aminonicotinamide resulted in a parallel inhibition of the conversion of acetoacetate and of glucose into fatty acids and into cholesterol. Glycolysis was also strongly inhibited in the presence of 6-aminonicotinamide whereas the activity of the Krebs cycle was not affected. These results suggest that de novo synthesis of fatty acids and cholesterol by oligodendrocytes of neonatal rats is closely geared to the activity of the pentose-phosphate pathway in these cells.