Carbonic anhydrase provides bicarbonate for de novo lipogenesis in the locust

The role of carbonic anhydrase (CA) in lipogenesis was investigated in the fat body of the desert locust (Schistocerca gregaria), an excellent model system for the study of fat metabolism. When reared in appropriate conditions, the locust passes through a period in development when its metabolism is strongly directed towards lipogenesis. This enhanced level of lipogenesis, which occurred in the 4- to 6-day old adult locust, was inhibited by the potent and specific sulphonamide inhibitors of CA, acetazolamide, methazolamide and ethoxzolamide, whilst the low levels of synthesis evident in the insect outside this lipogenic period remained unaffected. The relative effectiveness of the three different sulphonamides in inhibiting lipogenesis correlated well with their effectiveness as inhibitors of carbonic anhydrase activity. Inhibition of lipogenesis by methazolamide was not overcome by the addition of bicarbonate (up of 25 mM) to the incubation medium. Consequently, these data suggest that inhibition is mediated through restriction of bicarbonate provision largely for pyruvate carboxylase in the mitochondrion rather than for acetyl CoA in the cytoplasma. We propose that carbonic anhydrase is necessary for the provision of bicarbonate for elevated levels of lipogenesis.