Direct anabolic metabolism of three-carbon propionate to a six-carbon metabolite occurs in vivo across tissues and species
AuthorDoan, Mary T.
Neinast, Michael D.
Varner, Erika L.
Bedi, Kenneth C., Jr.
Singh, Jay P.
Rame, J. Eduardo
Brady, Donita C.
Meier, Jordan L.
Marguiles, Kenneth B.
GroupCenter for Metabolic Disease Research (Temple University)
Microbiology, Immunology and Inflammation
Stable isotope tracing
Permanent link to this recordhttp://hdl.handle.net/20.500.12613/9646
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AbstractAnabolic metabolism of carbon in mammals is mediated via the one- and two-carbon carriers S-adenosyl methionine and acetyl-coenzyme A. In contrast, anabolic metabolism of three-carbon units via propionate has not been shown to extensively occur. Mammals are primarily thought to oxidize the three-carbon short chain fatty acid propionate by shunting propionyl-CoA to succinyl-CoA for entry into the TCA cycle. Here, we found that this may not be absolute as, in mammals, one nonoxidative fate of propionyl-CoA is to condense to two three-carbon units into a six-carbon trans-2-methyl-2-pentenoyl-CoA (2M2PE-CoA). We confirmed this reaction pathway using purified protein extracts provided limited substrates and verified the product via LC-MS using a synthetic standard. In whole-body in vivo stable isotope tracing following infusion of 13C-labeled valine at steady state, 2M2PE-CoA was found to form via propionyl-CoA in multiple murine tissues, including heart, kidney, and to a lesser degree, in brown adipose tissue, liver, and tibialis anterior muscle. Using ex vivo isotope tracing, we found that 2M2PE-CoA also formed in human myocardial tissue incubated with propionate to a limited extent. While the complete enzymology of this pathway remains to be elucidated, these results confirm the in vivo existence of at least one anabolic three- to six-carbon reaction conserved in humans and mice that utilizes propionate.
CitationMary T. Doan, Michael D. Neinast, Erika L. Varner, Kenneth C. Bedi, David Bartee, Helen Jiang, Sophie Trefely, Peining Xu, Jay P. Singh, Cholsoon Jang, J. Eduardo Rame, Donita C. Brady, Jordan L. Meier, Kenneth B. Marguiles, Zoltan Arany, Nathaniel W. Snyder, Direct anabolic metabolism of three-carbon propionate to a six-carbon metabolite occurs in vivo across tissues and species, Journal of Lipid Research, Volume 63, Issue 6, 2022, 100224, ISSN 0022-2275, https://doi.org/10.1016/j.jlr.2022.100224.
Citation to related workElsevier
Has partJournal of Lipid Research (JLR), Vol. 63, Iss. 6
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