Loss of Propionyl-CoA Carboxylase Reprograms Hepatic Metabolism by Suppressing Mitochondrial Pyruvate Carboxylation and Fatty Acid Oxidation
knockout HepG2 cells. Threonine showed minimal metabolic contribution in this model, further supporting the role of propionate as a major source of propionyl-CoA production. Collectively, these findings highlight the metabolic vulnerabilities associated with PCC deficiency and underscore the increased risk of prolonged fasting in patients with PA, particularly those with severe disease.
Authors
- Chorlada Paiboonrungruang
- Takhar Kasumov (ORCID: https://orcid.org/0000-0003-2173-7231)
- Lu Fang (ORCID: https://orcid.org/0000-0002-8258-784X)
- Guofang Zhang (ORCID: https://orcid.org/0000-0002-4616-2721)
- Xiaoxin Luke Chen (ORCID: https://orcid.org/0000-0002-4792-6156)
- Wentao He (ORCID: https://orcid.org/0009-0003-3293-9581)
- Pingchuan Tang
- Zhaohui Xiong
Institutions
- Duke University (US)
- Coriell Institute For Medical Research (US)
- Duke Medical Center (US)
- Cooper University Health Care (US)
- Northeast Ohio Medical University (US)
Publication Details
- Journal
- bioRxiv (Cold Spring Harbor Laboratory)
- Published
- 2026-04-15
- DOI
- https://doi.org/10.64898/2026.04.13.718201
- Primary Topic
- Metabolism and Genetic Disorders
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Propionic Acidemia Foundation
- National Institutes of Health