Property and activity of mycoloyl esters of methyl glucoside and trehalose. Effect on mitochondrial oxidative phosphorylation related to organization of suspensions and to acyl-chain structures.
Methyl alpha-D-glucoside and alpha, alpha'-D-trehalose acylated on their primary hydroxyl group by alpha-alkyl-beta-hydroxy acids (mycolic acids) with 18, 32 and more than 80 carbon atoms were studied. These cord factors and analogues when dispersed in water gave hydrated and organized phases which bore resemblances and differences to phospholipid liposomes. Phase transition temperature was determined by fluorescence for the C32 derivatives and by differential scanning calorimetry for the C80 derivatives. A narrow temperature interval between the gel and the fluid states was observed, indicating that this transition was a strongly cooperative phenomenon. The activity on mitochondria of these diacyl trehaloses was studied with succinate as substrate. The fluid suspensions were more active than the rigid ones. There was no influence of the relative configuration of the mycoloyl residue. Acyl chains with 18, 32 and more than 80 carbon atoms had rather similar activities on phosphorylation, but differences appeared when considering effects on respiration. Electron microscopy suggested that cord factor weakened the peripheral part of the inner membrane, but cristae looked unchanged. These observations, together with the results of our previous monolayer studies of these glycolipids, led us to propose a model for interaction of cord factor with mitochondria.
D000818:Animals; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D003311:Cord Factors / Q000494:pharmacology*; D004187:Disaccharides / Q000494:pharmacology*; D004952:Esters; D005260:Female; D006017:Glycolipids / Q000494:pharmacology*; D008560:Membrane Fluidity; D008757:Methylglucosides / Q000494:pharmacology; D008759:Methylglycosides / Q000494:pharmacology; D008930:Mitochondria, Liver / Q000187:drug effects; D008968:Molecular Conformation; D009171:Mycolic Acids / Q000494:pharmacology; D010085:Oxidative Phosphorylation / Q000187:drug effects; D051381:Rats; D013329:Structure-Activity Relationship; D013696:Temperature; D014199:Trehalose / Q000031:analogs & derivatives / Q000494:pharmacology
D003311:Cord Factors; D004187:Disaccharides; D004952:Esters; D006017:Glycolipids; D008757:Methylglucosides; D008759:Methylglycosides; D009171:Mycolic Acids; D014199:Trehalose