Reassessment of sup 14 CO sub 2 compartmentation and of ( sup 14 C)formate oxidation in rat liver

Our previous report had concluded that a fraction of ({sup 14}C)formate oxidation in liver occurs in the mitochondrion. This conclusion was based on the labeling patterns of urea and acetoacetate labeled via {sup 14}CO{sub 2} generated from ({sup 14}C)formate and other ({sup 14}C)substrates. We reassessed our interpretation in experiments conducted in (i) perifused mitochondria and (ii) isolated livers perfused with buffer containing ({sup 14}C)formate, ({sup 14}C)gluconolactone, {sup 14}CO{sub 2}, or NaH{sup 13}CO{sub 3}, in the absence and presence of acetazolamide, an inhibitor of carbonic anhydrase. Our data show that the cytosolic pools of bicarbonate and CO{sub 2} are not in isotopic equilibrium when {sup 14}CO{sub 2} is generated in the cytosol or is supplied as NaH{sup 14}CO3. We retract our earlier suggestion of a mitochondrial site of ({sup 14}C)formate oxidation.