The biosynthesis of isoprenoid lipids including ubiquinone in muscle from normal and genetically dystrophic mice

Abstract

The concentration and rates of biosynthesis of ubiquinone, squalene, and cholesterol were studied in muscle from genetically dystrophic mice and their heterozygous normal littermates. The biosynthesis of ubiquinone from its 14C-benzoic acid precursor was studied in vivo, and from its isoprenoid sidechain precursor 2- 14C-MVA lactone, in vitro. The ubiquinone and cholesterol content per gram of dystrophic skeletal muscle was increased above normal 80–100%, whereas squalene concentration was unchanged. The rate of biosynthesis of ubiquinone was increased in dystrophic muscle by a factor of 1.5–3.4 over controls. The mitochondrial content of ubiquinone in normal and dystrophic muscle was the same, but extramitochondrial ubiquinone was increased in the dystrophic mouse. Succinic dehydrogenase activities were also unchanged in mitochondria from dystrophic muscle. These data do not support the view that a deficiency of ubiquinone exists in the dystrophic muscle. In fact, the excess in synthesis of ubiquinone and squalene indicate a disturbance in the regulation of the biosynthesis of isoprenoid compounds in muscle which may be intrinsic to the genetic disorder of muscular dystrophy.