The Glyoxylate Cycle in Rat Epiphyseal Cartilage: The Effect of Vitamin D₃ on the Activity of Enzymes Isocitrate Lyase and Malate Synthase

Abstract

The effect of vitamin D deficiency and subsequent vitamin D replacement on the metabolism of rat epiphyseal growth plate cartilage was studied. Biochemical analysis of cartilage showed the presence of two unique glyoxylate cycle enzymes (isocitrate lyase and malate synthase) whose activity was markedly increased after treatment with vitamin D. Additionally, rat cartilage demonstrated the ability to oxidize fatty acid in the presence of cyanide, characteristic of peroxisomal β-oxidation rather than mitochondrial β-oxidation. Vitamin D treatment also increased fatty acid oxidation. Finally, incubation of rat cartilage in the presence of a fatty acid substrate, such as palmitate, resulted in a higher tissue glycogen content. Tissue glycogen production was further enhanced by vitamin D. Such data indicate the presence of glyoxylate cycle enzymes in a vertebrate tissue and raise the possibility that mammalian cartilage can convert lipid to carbohydrate. A thorough evaluation of certain human clinical conditions indicates a potential relationship between peroxisomes, fatty acid β-oxidation by peroxisomes, and a peroxisomal glyoxylate cycle.