Inhibition of rat brain lipid synthesis in vitro by 4-hydroxybutyric acid

4-Hydroxybutyric acid (4HB) is accumulated in succinic semialdehyde dehydro genase deficiency, an inherited metabolic disease severely affecting the CN S during postnatal development. Thus, the present study was designed to eva luate the in vitro influence of 4HB on lipid synthesis and CO2 production f rom [U-C-14] acetate in cerebral cortex of 30-day-old Wistar rats. In the p resence of 4HB, there was an inhibition of lipid synthesis in cerebral cort ex prisms and homogenates. However, no inhibition of lipid synthesis occurr ed in the homogenates free of nuclei and mitochondria. In addition, CO2 pro duction was inhibited by 4HB in cerebral cortex prisms, and homogenates and in the mitochondrial fraction. These results might possibly be explained b y an impairment of mitochondrial metabolism by 4HB which may secondarily in hibit lipid synthesis. The results reported here may help to better underst and the neuropathophysiology of I-hydroxybutyric aciduria.