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 excelle nt model system for the study of fat metabolism. When reared in approp riate conditions, the locust passes through a period in development wh en its metabolism is strongly directed towards lipogenesis. This enhan ced level of lipogenesis, which occurred in the 4- to 6-day old adult locust, was inhibited by the potent and specific sulphonamide inhibito rs of CA, acetazolamide, methazolamide and ethoxzolamide, whilst the l ow levels of synthesis evident in the insect outside this lipogenic pe riod remained unaffected. The relative effectiveness of the three diff erent sulphonamides in inhibiting lipogenesis correlated well with the ir effectiveness as inhibitors of carbonic anhydrase activity. Inhibit ion of lipogenesis by methazolamide was not overcome by the addition o f bicarbonate (up of 25 mM) to the incubation medium. Consequently, th ese data suggest that inhibition is mediated through restriction of bi carbonate provision largely for pyruvate carboxylase in the mitochondr ion rather than for acetyl CoA in the cytoplasma. We propose that carb onic anhydrase is necessary for the provision of bicarbonate for eleva ted levels of lipogenesis.