Cytochrome oxidase phospholipid interaction

Knowles, P.F., Watts, A., and Marsh, D., 1981, Spin label studies of headgroup specificity in the interaction of phospholipids with yeast cytochrome oxidase. Biochemistry, 20 5888. 

Doxombicin binds readily to ceU membranes, changing their structure and function. The targets of doxombicin binding are compounds with a negative charge, of which the most extensively studied is the phospholipid cardiolipin (Pollakis et ah, 1983). Cardiolipin occurs in high concentrations in the inner mitochondrial membrane, where it is required for full activity of cytochrome c oxidase. In a recent study (Das and Mazumdar, 2000), the interaction between cytochrome c oxidase and cardiohpin in the presence of doxombicin was analysed, and the results of pico-second time-resolved fluorescence depolarization showed that the cardiohpin layer was depleted due to complexation with the dmg. 

For most drugs, oxidative biotransformation is performed primarily by the mixed-function oxidase enzyme system, which is present predominantly in the smooth endoplasmic reticulum of the liver. This system comprises (1) the enzyme NADPH cytochrome P450 reductase (2) cytochrome P450, a family of heme-containing proteins that catalyze a variety of oxidative and reductive reactions and (3) a phospholipid bilayer that facilitates interaction between the two proteins. Important exceptions to this rule are ethyl alcohol and caffeine, which are oxidatively metabolized by enzymes primarily present in the soluble, cytosolic fraction of the liver. 

Inhibition of cytochrome c oxidase, interaction with phospholipids 358... 

While cyanide inhibition of cytochrome c oxidase may not account for the full spectrum of toxicity in CS exposure, cyanide toxicity may include an array of biochemical interactions (Way, 1984). These include lipid peroxidation (Johnson et al, 1987), cyanide release of endogenous opioids to cause respiratory paralysis (Leung et al, 1986), disruption of neuronal calcium homeostasis (Johnson et al, 1986), and phospholipids hydrolysis (Sakaida and Farber,... 

The situation is even worse for membrane lipids. Not a single, naturally occurring phospholipid with unsaturated hydrocarbon chains has yet been crystallized. However, nearly 40 crystal structures of closely related synthetic glycerolipids with saturated hydrocarbon chains have been solved by X-ray. On the structural level, little is known about the interactions of proteins with lipid bilayer environments. Detergent molecules have been detected in some of the X-ray structures, and a small number of studies discuss lipids bound to proteins. An example is cytochrome C oxidase crystals, where the lipids were found to be arranged in a bilayer structure. 

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