Abstract
Following preincubation of isolated rat liver mitochondria in the absence of substrate, the carnitine-independent oxidation of octanoate or butyrate was markedly depressed when compared to rates observed with nonpreincubated mitochondria. Carnitine addition prevented the inhibition of octanoate oxidation but not that of butyrate. 2-Tetradecylglycidic acid or Zwittergent 3-08 (Z3-08) completely blocked the effect of carnitine. Replacement of ATP in the nonpreincubated incubation system with ADP mimicked the effect of preincubation by inhibiting octanoate and butyrate oxidation. This inhibition of octanoate oxidation was also prevented by carnitine addition. There was a direct and causal relationship between the ATP/ADP ratio of the total adenine nucleotide pool and the rate of carnitine-independent octanoate oxidation in mitochondria. The depression of octanoate oxidation was associated with a decrease in the intramitochondrial AMP content and intra- and extramitochondrial ATP/ADP ratios. In a cellular system, incubating isolated hepatocytes with fructose or glycerol to lower the ATP/ADP ratio resulted in greater inhibition of octanoate oxidation by 2-tetradecylglycidic acid. The data suggest that the ATP/ADP ratio may have a role in determining the site of octanoate activation and subsequent route of oxidation.
Highlights
ADP ratio resulted in greater inhibition of octanoate oxidation by 2-tetradecylglycidic acid
The data suggest that the ATP/ADP ratio may have a role in determining the siteof octanoate activation and subsequent route of oxidation
While investigating the inhibitoryaction of 5-(tetradecy1oxy)-2-furoic acid on the oxidation of palmitate (I),’ we observed a slight (15%)inhibition of octanoate oxidation by TOFA’ in hepatocytes. This effect was not consistent with our other observations which suggested that TOFA competed for cytosolic CoA, depressing extramitochondrial activation of fatty acids
Summary
ADP ratio resulted in greater inhibition of octanoate oxidation by 2-tetradecylglycidic acid. The data suggest that the ATP/ADP ratio may have a role in determining the siteof octanoate activation and subsequent route of oxidation. With the subsequent addition and intrarnitochondrial activation of octanoate or butyrate, there would be an excessive elevation of matrix AMP due to low GTP levels and a resulting inhibition of intramitochondrial fatty acid activation (see Miniprint).
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
