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Review
. 2025 Feb 4;37(2):316-329.
doi: 10.1016/j.cmet.2025.01.005.

The emerging role of dysregulated propionate metabolism and methylmalonic acid in metabolic disease, aging, and cancer

Moniquetta Shafer  1 , Vivien Low  2 , Zhongchi Li  3 , John Blenis  4
Affiliations
Review

The emerging role of dysregulated propionate metabolism and methylmalonic acid in metabolic disease, aging, and cancer

Moniquetta Shafer et al. Cell Metab. .

Abstract

Propionate metabolism dysregulation has emerged as a source of metabolic health alterations linked to aging, cardiovascular and renal diseases, obesity and diabetes, and cancer. This is supported by several large cohort population studies and recent work revealing its role in cancer progression. Mutations in several enzymes of this metabolic pathway are associated with devastating inborn errors of metabolism, resulting in severe methylmalonic and propionic acidemias. Beyond these rare diseases, however, the broader pathological significance of propionate metabolism and its metabolites has been largely overlooked. Here, we summarize earlier studies and new evidence that the alteration of this pathway and associated metabolites are involved in the development of various metabolic diseases and link aging to cancer progression and metastasis.

Keywords: BCAA metabolism; BCAAs; MMA; aging; branched-chain amino acids; cancer metabolism; metabolic disorders; methylmalonic acid; methylmalonyl-CoA; propionate; propionyl-CoA.

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Conflict of interest statement

Declaration of interests J.B. and Z.L. are the founders of Elikia Inc., which targets aging-related metabolic dysfunction for the treatment of aging-related diseases.

References

    1. Duesberg PH, and Vogt PK (1970). Differences between the ribonucleic acids of transforming and nontransforming avian tumor viruses. Proc Natl Acad Sci U S A 67, 1673–1680. 10.1073/pnas.67.4.1673. - DOI - PMC - PubMed
    1. Hanahan D, and Weinberg RA (2011). Hallmarks of cancer: the next generation. Cell 144, 646–674. 10.1016/j.cell.2011.02.013. - DOI - PubMed
    1. Pavlova NN, and Thompson CB (2016). The Emerging Hallmarks of Cancer Metabolism. Cell Metab 23, 27–47. 10.1016/j.cmet.2015.12.006. - DOI - PMC - PubMed
    1. Seok J, Yoon SH, Lee SH, Jung JH, and Lee YM (2019). The oncometabolite d‑2‑hydroxyglutarate induces angiogenic activity through the vascular endothelial growth factor receptor 2 signaling pathway. Int J Oncol 54, 753–763. 10.3892/ijo.2018.4649. - DOI - PubMed
    1. Bunse L, Pusch S, Bunse T, Sahm F, Sanghvi K, Friedrich M, Alansary D, Sonner JK, Green E, Deumelandt K, et al. (2018). Suppression of antitumor T cell immunity by the oncometabolite (R)-2-hydroxyglutarate. Nat Med 24, 1192–1203. 10.1038/s41591-018-0095-6. - DOI - PubMed

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