nor the inhibition in the homogenates with intermediate concentrations tested.
There are a few other comments to be made. The authors report that, when normal hepatocytes were incubated with 5 m M hypoglycin, gluconeogenesis from lactate was inhibited, but G6Pase activity was not. This comment is misleading, since the residual gluconeogenic activity was greater when hepatocytes were incubated with 5 mM hypoglycin (63%) than when incubated with a mixture of four natural amino acids (leu, ile, lys, and trp: 1 m M each) without hypoglycin (30%). Therefore, this moderate inhibition of gluconegenesis is not due to the specific inhibitory action of hypoglycin. When hepatocytes were used, the keto analog, rather than hypoglycin itself, should have been used as an inhibitor, since hypoglycin is probably transaminated by the same branched-chain amino acid transaminase which is mainly distributed in extrahepatic tissues.
The title of the paper is misleading, since it gives the impression that the results elucidate the major mechanisms for the hypoglycemic action of hypoglycin-far from it! It is unfortunate that in the "Introduction" and "Discussion," the authors have ignored a number of pertinent contributions by others and instead relied heavily on their own review articles, one of which was written almost two decades ago. For key facts, original papers should always be cited.