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MINI REVIEW article
Front. Mol. Neurosci.
Sec. Brain Disease Mechanisms
Volume 18 - 2025 | doi: 10.3389/fnmol.2025.1499376
Elevated propionate and its association with neurological dysfunctions in propionic acidemia
Provisionally accepted- 1 Coriell Institute For Medical Research, Philadelphia, United States
- 2 North Carolina Central University, Durham, North Carolina, United States
- 3 Duke University, Durham, United States
Propionate, a short-chain fatty acid (SCFA), has recently attracted attention for its various health benefits. However, elevated levels of propionate in certain pathological conditions can have adverse effects. Propionic acidemia (PA) is a rare metabolic disorder caused by mutations in the propionyl-CoA carboxylase (PCC) gene (PCCA or PCCB), leading to reduced PCC activity and impaired propionyl-CoA metabolism. This metabolic block at the PCC-mediated step results in the accumulation of propionyl-CoA and its metabolites, including propionate, contributing to various complications, such as neurological dysfunction, in patients with PA. This review examines propionate synthesis, its physiological role, its metabolism in healthy individuals and those with PA, and the pathological link between elevated propionate levels and neurological dysfunctions in PA patients. A deeper understanding of propionate metabolism under both normal and pathological conditions will help clarify the full spectrum of its metabolic effects.
Keywords: Propionic Acidemia, Propionate (PubChem CID: 1032), Neurological dysfunction, microbiome, short-chain fatty acids, Rare metabolic diseases, Metabolism
Received: 23 Sep 2024; Accepted: 03 Mar 2025.
Copyright: © 2025 Chen, Cheng and Zhang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Xiaoxin Chen, Coriell Institute For Medical Research, Philadelphia, 19112, United States
Guo-Fang Zhang, Duke University, Durham, United States
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.