Palmitate oxidation

Two and twelve moles of ATP are produced, respectively, per mole of glucose consumed in the glycolytic pathway and each turn of the Krebs (citrate) cycle. In fat metaboHsm, many high energy bonds are produced per mole of fatty ester oxidized. Eor example, 129 high energy phosphate bonds are produced per mole of palmitate. Oxidative phosphorylation has a remarkable 75% efficiency. Three moles of ATP are utilized per transfer of two electrons, compared to the theoretical four. The process occurs via a series of reactions involving flavoproteins, quinones such as coenzyme Q, and cytochromes. 

Figure 8-4. 3-Oxidation of palmitate. Oxidation of an even-numbered, saturated fatty acid involves repetitive cleavage at the (1 carbon of the acyl chain. Removal of two-carbon units occurs in a cycle of four steps initiated by one of the acyl CoA dehydrogenases. Acetyl CoA is produced at each cycle until all that remains of the acyl CoA is acetyl CoA itself.

The sensitivity of CPT I from different tissues to POCA and MeTDGA varies, as does its sensitivity to malonyl-CoA [88,92,96,97]. Studies in which MeTDGA was administered in vivo followed by isolation of mitochondria from various tissues showed that liver CPT I was most sensitive to the inhibitor, followed by heart and then diaphragm [97], A similar pattern of tissue sensitivity was observed with POCA [88, 92]. Preliminary studies comparing the effects of emeriamine in isolated hepatocytes and cardiomyocytes showed the hepatocytes to be 10-fold more sensitive than the cardiomyocytes when palmitate oxidation or CPT I activity was used as a measure of effectiveness [90]. 

The inhibition of CPT I by either POCA or MeTDGA caused a decrease in [ l4C]palmitate oxidation. MeTDGA effectively inhibited palmitate oxidation in kidney cortex slices [98], diaphragm [98], heart [99] and hepatocytes [ 100] from fasted rats. POCA produced an almost complete suppression of long-chain fatty acid oxidation in the perfused rat heart from either fed or fasted animals [101]. POCA also inhibited hepatocyte oxidation of oleate up to 85% with maximal effects of POCA observed at concentrations as low as 1 /xM... 

See also Palmitate, Oxidation of Saturated Fatty Acids... 

The total number of water molecules produced is 146, and the net water produced is (146 -F 23) -F 123 molecules of water per palmitate oxidized or 123 moles of water per mole of palmitate. The molecular weight of water is 18.0 g mol F... 

Lopez-Cardozo, M., Klazinga, W. van den Bergh, S.G. (1978) E wr. J. Biochem. 83, 629-634. Accumulation of carnitine esters of beta-oxidation intermediates during palmitate oxidation in rat liver mitochondria. 

Smith, BK Jain, SS Rimbaud, S Dam, A Quadrilatero, J Ventura-Clapier, R et al. FAT/CD36 is located on the outer mitochondrial membrane, upstream of long-chain acyl-CoA synthetase, and regulates palmitate oxidation. Biochem J, 2011 437 125-34. 

Heinonen, O.J., Carnitine Effect on Palmitate Oxidation, Exercise Capacity and Nitrogen Balance. An Experimental Study with Special Reference to Carnitine Depletion and Supplementation. Ph.D. dissertation. University of Turku, Einland, 1992. Feller, A.G. and Rudman, D., Role of carnitine in human nutrition. J. Nutr., 118, 541-547, 1988. 

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. 

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