VARIATIONS IN LIPID INTAKE AND THEIR INFLUENCE ON RESPIRATION AND TRICARBOXYLIC ACID CYCLE ACTIVITY

Abstract

The possible role of dietary lipids and lipid-soluble constituents in the tricarboxylic acid cycle, respiratory systems, and mitochondrial structure is discussed, with special emphasis on vitamin D, vitamin A, and essential fatty acids. Deficiency of any of these substances produces structural alterations in isolated kidney or liver mitochondria. In the case of vitamin D deficiency the structural alteration in kidney mitochondria is accompanied by an increased rate of citrate and isocitrate oxidation and a decreased transfer of calcium ions from inside to outside the mitochondria. Vitamin D added in vitro or given to the intact rat specifically decreases citrate oxidation and increases the translocation of calcium. Vitamin A deficiency increases the respiration of liver homogenates and mitochondria in the absence of phosphate acceptor, an effect which could readily be reversed within 48 hours after vitamin A administration. Increased ATPase and decreased respiratory control were also noted in liver mitochondria from vitamin A deficient rats. The structural change as well as the biochemical lesions could also be reversed within 48 hours after vitamin A administration. Similar experiments with essential fatty acid deficient mitochondria also revealed a high ATPase, low respiratory control, and marked structural damage. These changes could be reversed by the feeding of essential fatty acids to the deficient animals for 1–3 weeks. Despite many attempts, it was not possible to demonstrate structural changes in mitochondria in situ as a result of any of the deficiencies described. It is suggested that the respiratory and tricarboxylic acid cycle changes that have been attributed to the lipid constituents of the diet are secondary to alterations in subcellular membrane systems. The use of these membrane systems as tools or models in a study of the mechanism of action of the dietary lipid and lipid-soluble materials is discussed.