Submit a comment
Citation Information: J Clin Invest. 1992;89(3):968-973. https://doi.org/10.1172/JCI115679.
Abstract
Previous studies have indicated that ketone body-mediated contractile failure in rat hearts is due to inhibition of 2-oxoglutarate dehydrogenase, and it has been speculated that this inhibition is due to the sequestration of intramitochondrial CoA as acetoacetyl-CoA and acetyl-CoA. These studies were performed to determine whether oxidation of acetoacetate by isolated rat heart mitochondria results in a fall in intramitochondrial nonesterified CoA [CoASH] and whether increasing the available CoA improves contractile performance in hearts oxidizing acetoacetate. The oxidation of acetoacetate by isolated rat heart mitochondria resulted in depressed state 3 respiration as well as in a decrease in [CoASH]. Increasing the tissue content of CoASH in perfused hearts by providing the precursors for CoA relieved inhibition of 2-oxoglutarate dehydrogenase and improved the contractile performance of isolated working hearts. In contrast, the addition of carnitine increased the tissue content of CoASH but did not improve function. These findings suggest the presence of two different pools of CoASH. We conclude that ketone body-mediated inhibition of 2-oxoglutarate dehydrogenase is due to decreased intramitochondrial CoASH and that this inhibition of the citric acid cycle is a plausible mechanism for concomitant contractile failure.
Authors
R R Russell 3rd, H Taegtmeyer
Guidelines
The Editorial Board will only consider comments that are deemed relevant and of interest to readers. The Journal will not post data that have not been subjected to peer review; or a comment that is essentially a reiteration of another comment.
- Comments appear on the Journal’s website and are linked from the original article’s web page.
- Authors are notified by email if their comments are posted.
- The Journal reserves the right to edit comments for length and clarity.
- No appeals will be considered.
- Comments are not indexed in PubMed.
Specific requirements
- Maximum length, 400 words
- Entered as plain text or HTML
- Author’s name and email address, to be posted with the comment
- Declaration of all potential conflicts of interest (even if these are not ultimately posted); see the Journal’s conflict-of-interest policy
- Comments may not include figures
Copyright © 2025 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)