Kinetic characteristics of citrate influx and efflux with mitochondria from Morris hepatomas 3924A and 16.

Carrier-mediated citrate transport has been demonstrated and characterized at 10°in mitochondria from Morris hepatomas 3924A and 16 and in normal and host liver preparations by the inhibitor-stop technique using 1,2,3-benzenetricarboxylate. We studied: (a) citrate influx in exchange for endogenous substrates; (b) citrate influx into mitochondria loaded with citrate; (c) citrate efflux from citrate-loaded mitochondria in exchange for either external citrate or malate; and (d) the temperature dependence of citrate efflux from citrate-loaded hepatoma 3924A mitochondria and its controls. At 10°,mito chondria from tumor 3924A displayed Kmand Vmaxvalues close to those of normal control liver mitochondria. Tumor 16 mito chondria exhibited similar Kmbut somewhat higher Vma« values relative to its normal control. As a function of temperature, however, the rate of citrate efflux from citrate-loaded hepatoma 3924A mitochondria differed dramatically from that of normal and host mitochondria. Biphasic Arrhenius plots characterized the normal and host liver preparations (discontinuities at 12.5° and 11.0°, respectively), whereas with tumor 3924A mitochon dria the plot was linear and indicated no phase transition temperature. Extrapolation to 37° indicated an apparent Vmax for citrate efflux from the tumor 3924A mitochondria that was 109% higher than that for normal liver mitochondria. Thus, at physiological temperature, hepatoma 3924A mitochondria may have the capacity to efflux citrate more rapidly than normal liver mitochondria. We speculate that an increased citrate transport capability correlates with the well-documented en hanced rate of cholesterogenesis in hepatomas and other fastgrowing tumors.