Specifically 14C-labeled
palmitic acids were perfused through livers and incubated with slices of kidneys from rats in
diabetic ketosis. The distribution of 14C in the hydroxybutyric
acid formed was determined. In liver, the ratio of incorporation of 14C from [13-14C]
palmitic acid into
carbon 1 to
carbon 3 of the hydroxybutyric
acid was the same as the ratio in
carbon 2 to
carbon 4 from [6-14C]
palmitic acid. In kidney, the
carbon 1-to-carbon 3 ratio was more than twice the
carbon 2-to-carbon 4 ratio. In both tissues, 14C from [16-14C]
palmitic acid was preferentially incorporated into
carbon 4 compared to
carbon 2 of the hydroxybutyric
acid, but more so in liver than kidney. These results mean that in liver, the sole pathway of
acetoacetate formation is via
hydroxymethylglutaryl-CoA, while in kidney it is not. Rather in kidney,
acetoacetyl-CoA is converted to
acetoacetate to a large extent by direct deacylation, presumably via a
transferase- and/or deacylase-catalyzed reaction. In liver, most of the
palmitic acid utilized is converted to
acetoacetate while in kidney it is not. We previously estimated that, as a minimum, 11% of the hydroxybutyric
acid excreted by the rat in
diabetic ketosis is formed without
hydroxymethylglutaryl-CoA as an intermediate. The kidney appears to be the source of this hydroxybutyric
acid if the pathways operative in these tissues in vitro are those that also operate in vivo.