Palmitate oxidation, pantethine

Effect of pantethine on palmitate oxidation was studied. Fig.3 shows the formation of radioactive CQz from l- C-palmitate as a function of CoA concentration in the liver and muscle homogenate obtained from normal rats. Addition of pantethine at 40 pM significantly stimulated the oxidative reaction of palmitate, but pantethine itself was not active unless CoA was present in the reaction mixture, as can be clearly seen with the muscle preparation. The similar results were obtained with the tissue homogenates from the diabetic rats. 

Fig.5 shows the effect of some pantethine derivatives on palmitate oxidation in the liver homogenates from both the normal and the... 

Fig.3. Effects of pantethine on palmitate oxidation in vitro. The reaction mixture contained 0.2 pmoles of sodium 1 -palmitate, 2 pmoles of ATP, 20 nmoles of CoA, 2 pmoles of L-carnitine and 100 pi of rat liver or muscle homogenate from normal rats in a total volume of 2 ml. After incubation of the mixture at 37 for 30 minutes, COlzformed was determined.

Fig.4. Effect of pantethine on palmitate oxidation in the muscle homogenate from diabetic rats. The experimental conditions were the same as in Fig.3, except for the muscle preparation from the diabetic rats.

Phosphopantetheine has been found to be the most active stimulant also in the overall palmitate oxidation to CO2 ( Fig.5 ). These findings suggest the major contribution of phosphopantetheine as an active principle to pantethine s action, because pantethine can be easily phosphorylated by pantothenate kinase in the cells [ 13 ]. 

The third and fourth possible sites may be excluded by the present results that acetoacetate formation from octanoic acid (lFig.7) and COa formation from l- C-octanoic acid ( Fig.6 ) were not affected by pantethine under the conditions where palmitate oxidation was stimulated by pantethine. If either of these two oxidation cycles could be affected by pantethine, octanoate oxidation in either system had to be stimulated, because octanoic acid is non-enzymatically permeable through the mitochondrial membranes. 

The second site may include two possibilities one is on the carnitine acyl transferase system and the other involves formation of palmitoyl-S-pantetheine and its non-enzymatic transport through the mitochondrial membranes followed by oxidation in -oxidation system after conversion to palmitoyl CoA. The former possibility may be supported by the difference in effectiveness of pantethine between the palmitate and octanoate oxidation reactions ( Fig.3, 4 and 6 ) and between the ketogenic reactions from these two substrates ( Fig.7 ), because octanoic acid is freely permeable through the mitochondrial membranes. The latter possibility was based on the findings on the formation of acyl pantetheine in rat liver micro-somes [ 10 ] and on the enzymatic interconversion between acyl CoA and acyl pantetheine [ 14 ] and on the much lower susceptibility of acyl pantetheine to3-oxidation than acyl CoA [ 14 ]. But this has been ruled out by the finding that palmitoyl-S-pantetheine did not serve as the substrate of the ketogenic reaction ( fig.7 ). 

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