Document Type
Article
Publication Date
8-13-2021
Publication Title
Metabolites
Abstract
Very long-chain acyl-CoA dehydrogenase deficiency (VLCADD, OMIM 609575) is associated with energy deficiency and mitochondrial dysfunction and may lead to rhabdomyolysis and cardiomyopathy. Under physiological conditions, there is a fine balance between the utilization of different carbon nutrients to maintain the Krebs cycle. The maintenance of steady pools of Krebs cycle intermediates is critical for mitochondrial energy homeostasis especially in high-energy demanding organs such as muscle and heart. Even-chain dicarboxylic acids are established as alternative energy carbon sources that replenish the Krebs cycle by bypassing a defective β-oxidation pathway. Despite this, even-chain dicarboxylic acids are eliminated in the urine of VLCAD-affected individuals. In this study, we explore dodecanedioic acid (C12; DODA) supplementation and investigate its metabolic effect on Krebs cycle intermediates, glucose uptake, and acylcarnitine profiles in VLCAD-deficient fibroblasts. Our findings indicate that DODA supplementation replenishes the Krebs cycle by increasing the succinate pool, attenuates glycolytic flux, and reduces levels of toxic very long-chain acylcarnitines.
Recommended Citation
Radzikh, Igor; Fatica, Erica; Kodger, Jillian; Shah, Rohan; Pearce, Ryan; and Sandlers, Yana, "Metabolic Outcomes of Anaplerotic Dodecanedioic Acid Supplementation in Very Long Chain Acyl-CoA Dehydrogenase (VLCAD) Deficient Fibroblasts" (2021). Chemistry Faculty Publications. 561.
https://engagedscholarship.csuohio.edu/scichem_facpub/561
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.
DOI
https://doi.org/10.3390/metabo11080538
Student Publication
This item is part of the McNair Scholars Program.
Volume
11
Issue
8
