Specifically 14C-labeled mevalonic
acids were administered to rats in
diabetic ketosis, and the distribution of 14C was determined in the hydroxybutyric
acid each rat excreted. Also, the distributions of 14C were determined in hydroxybutyric
acid formed by slices of livers and kidneys from rats in
diabetic ketosis and incubated with the specifically labeled mevalonic
acids. The distributions found are in accord with the conversion of
mevalonate to
hydroxymethylglutaryl-CoA by the shunt pathway proposed by J. Edmond and G. Popják ((1974) J. Biol. Chem. 249, 66-71). That is,
carbon 5 of
mevalonate was metabolized to form the carboxyl of
acetyl-CoA and carbons 2 and 3 of
mevalonate were converted in large measure to hydroxybutyric
acid without
acetyl-CoA as an intermediate, i.e. the bond between
carbon 2 and 3 was not cleaved, while the bond between 1 and 2, traced with [1,2-14C]
mevalonate, was cleaved. Similar distributions of 14C were found in hydroxybutyric
acid excreted by rats in
diabetic ketosis administered specifically 14C-labeled isovaleric
acids,
isovaleric acid having in its metabolism intermediates common to those in the shunt pathway.