Medium-Chain, Even-Numbered Dicarboxylic Acids as Novel Energy Substrates: An Update

Abstract

Medium-chain dicarboxylic acids are produced by higher plants and animals via fatty acid -oxidation or by ␤-oxidation of longer-chain dicarboxylic acids. In plants, dicarboxylic acids are components of the natural protective polymers cutin and suberin; in animals, dicarboxylic acids are mainly oxidized in mitochondria, where they are transported through four different pathways. Their energy density is intermediate between glucose and fatty acids. Dicarboxylic acid administration does not require insulin or stimulate insulin secretion, and the ␤-oxidation of dicarboxylic acids produces succinic acid, a gluconeogenic substrate. Therefore, dicarboxylic acids might be a suitable fuel substrate, particularly in clinical conditions in which marked insulin resistance and/or impairment of aerobic glycolysis occur.

Metabolic Outcomes of Anaplerotic Dodecanedioic Acid Supplementation in Very Long Chain Acyl-CoA Dehydrogenase (VLCAD) Deficient Fibroblasts

“…For instance, triheptanoin (DOJOLVI TM ), an anaplerotic C7-triglyceride was recently approved by FDA for LC-FOAD management. Medium even-chain dicarboxylic acids (C6-C12) also exhibit anaplerotic characteristics and effectively replenish Krebs cycle intermediates with efficient energetic values [21,22].…”

“…Even-chain dicarboxylic acids (DAs) also exhibit anaplerotic characteristics and have been proposed as an alternative energy substrate [21]. DAs are produced endogenously through the corresponding fatty acid ω-oxidation or from the β-oxidation of longer dicarboxylic acids.…”

“…DAs (C6-C12) metabolism in mitochondria and peroxisomes, yields a Krebs cycle intermediate and gluconeogenic precursor succinyl-CoA. Due to their anaplerotic effect and high energy density [22], DAs were proposed as an alternative fuel energy substrate in parental nutrition [21][22][23]. It is evident however that overproduction and accumulation of hepatic DA are toxic [24].…”

The urinary metabolome in female mink (Mustela neovison) shows distinct changes in protein and lipid metabolism during the transition from diapause to implantation

“…Dicarboxylic acids are derived either by β-oxidation of longer-chain dicarboxylic acids or by ω-oxidation in the microsomal membranes (Mingrone and Castagneto 2006). Dicarboxylic acids are β-oxidized in the peroxisomes and mitochondria (Mingrone et al 2013).…”

3D-Printable Biodegradable Polyester Tissue Scaffolds for Cell Adhesion

“…5000 mg kg À1 . [40] Even-chain diacids, including adipic acid, are partially metabolized in human mitochondria [41] to form acetyl CoA and succinyl CoA, which represent the starting point or an intermediate in the Krebs cycle respectively, [5] and unmodified adipic acid is typically excreted in urine. [40] Additionally, TEG exhibits significantly reduced toxicity as compared with its lower-molecular-weight analogues, di(ethylene glycol) and ethylene glycol.…”