The modes of action of long chain alkyl compounds on the respiratory chain-linked energy transducing system in submitochondrial particles.
The interactions of long chain (greater than C7), alkyl compounds with tightly coupled, beef heart submitochondrial particles (SMP) have been investigated with respect to their effects upon respiratory chain-linked electron transfer and energy coupling capacity. Long chain alkyl alcohols, amines, free fatty acids, and methyl esters exhibit a general uncoupling effect, with stimulation of the succinate oxidase activity but inhibition of the NADH oxidase, in SMP. The degree of effectiveness is dependent on the nature of the functional group and the length of the alkyl chain. Submitochondrial particles depleted of F1 and the F1-inhibitor protein are similarly affected. Subsequent treatment with bovine serum albumin reverses the effects of free fatty acids and results in partial recovery of activity with alkyl amines, alcohols, and methyl esters. Differences between the effects of these alkyl compounds and those of sodium dodecyl sulfate, deoxycholate, palmitoyl carnitine, and palmitoyl CoA rule out detergent-like action as the explanation for these observations. These data suggest that specific lipophilic interactions with the membrane, modulated by the nature of the functional group, are responsible for the effects of these compounds on the energy transducing system of SMP. Analyses of the reduction kinetics of the cytochromes indicate that the sites of interaction of these compounds with the inner mitochondrial membrane are associated with the primary dehydrogenase of complex I and energy coupling site 2; alkyl amines possess an additional site of interaction in the region of complex III.
D000438:Alcohols / Q000494:pharmacology*; D000588:Amines / Q000494:pharmacology*; D000818:Animals; D002264:Carboxylic Acids / Q000494:pharmacology*; D002417:Cattle; D003580:Cytochromes / Q000378:metabolism; D003902:Detergents / Q000494:pharmacology; D004579:Electron Transport / Q000187:drug effects*; D004952:Esters / Q000494:pharmacology*; D005230:Fatty Acids, Nonesterified / Q000494:pharmacology*; D066298:In Vitro Techniques; D019814:Myristic Acid; D009227:Myristic Acids / Q000494:pharmacology; D006180:Proton-Translocating ATPases / Q000378:metabolism; D012710:Serum Albumin, Bovine / Q000494:pharmacology; D013367:Submitochondrial Particles / Q000187:drug effects* / Q000378:metabolism
D000438:Alcohols; D000588:Amines; D002264:Carboxylic Acids; D003580:Cytochromes; D003902:Detergents; D004952:Esters; D005230:Fatty Acids, Nonesterified; D009227:Myristic Acids; D019814:Myristic Acid; D012710:Serum Albumin, Bovine; D006180:Proton-Translocating ATPases