Dietary fatty acids are metabolized into fuel sources using beta-oxidation. Fatty acid conversion into Acetyl-CoA requires transport across the mitochondrial membrane via the carnitine shuttle. When beta-oxidation is impaired, fats are metabolized using an alternate pathway called omega-oxidation. Omega-oxidation results in elevated levels of dicarboxylic acids such as adipic acid and suberic acid. Impaired beta-oxidation occurs in carnitine deficiency or enzymatic dysfunction due to lack of nutrient cofactors. Vitamin B2 and magnesium play a role in optimizing beta-oxidation.
- Sharma S, Black SM. Carnitine homeostasis, mitochondrial function, and cardiovascular disease. Drug Discov Today Dis Mechanisms. 2009;6(1-4):e31-e39.
- Kaluzna-Czaplinska J, Socha E, Rynkowski J. B vitamin supplementation reduces excretion of urinary dicarboxylic acids in autistic children. Nutr Res. 2011;31(7):497-502.
- Altura BM, Gebrewold A, Altura BT, Brautbar N. Magnesium depletion impairs myocardial carbohydrate and lipid metabolism and cardiac bioenergetics and raises myocardial calcium content in-vivo: relationship to etiology of cardiac diseases. Biochem Mol Biol Int. 1996;40(6):1183-1190.
- Nagao M, Tanaka K. FAD-dependent regulation of transcription, translation, post-translational processing, and post-processing stability of various mitochondrial acyl-CoA dehydrogenases and of electron transfer flavoprotein and the site of holoenzyme formation. J Biol Chem. 1992;267(25):17925-17932.
- Olsen Rikke K, Konarikova E, Giancaspero Teresa A, et al. Riboflavin-Responsive and -Non-responsive Mutations in FAD Synthase Cause Multiple Acyl-CoA Dehydrogenase and Combined Respiratory-Chain Deficiency. Am J Human Genet. 2016;98(6):1130-1145.
- Green A, Marshall T, Bennett M, Gray R, Pollitt R. Riboflavinresponsive ethylmalonic - adipic aciduria. J Inh Metab Dis. 1985;8(2):67-70.
- Liang W-C, Tsai K-B, Lai C-L, Chen L-H, Jong Y-J. Riboflavinresponsive glutaric aciduria type II with recurrent pancreatitis. Pediatr Neurol. 2004;31(3):218-221.
- Gregersen N. Riboflavin-responsive defects of beta-oxidation. J Inher Metab Dis. 1985;8 Suppl 1:65-69.
- Villarreal-Perez JZ, Villarreal-Martinez JZ, Lavalle-Gonzalez FJ, et al. Plasma and urine metabolic profiles are reflective of altered betaoxidation in non-diabetic obese subjects and patients with type 2 diabetes mellitus. Diabetol Metab Syndr. 2014;6:129.
- Chang B, Nishikawa M, Nishiguchi S, Inoue M. L-carnitine inhibits hepatocarcinogenesis via protection of mitochondria. Int J Cancer Journal. 2005;113(5):719-729.
Elevated levels of adipic and suberic acid may reflect insufficient carnitine or lack of nutrient cofactors for proper beta-oxidation.
Clinical Associations: Increased omega-oxidation metabolites can be seen in ketosis, insulin resistance, diabetes, fasting, or low carbohydrate intake. Elevations of suberic and adipic acid can lead to further mitochondrial dysfunction by injuring the cell membrane and producing free-radical damage.
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