Direct anabolic metabolism of three-carbon propionate to a six-carbon metabolite occurs in vivo across tissues and species
Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved..
Anabolic 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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2022 |
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| Erschienen: |
2022 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:63 |
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| Enthalten in: |
Journal of lipid research - 63(2022), 6 vom: 01. Juni, Seite 100224 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Doan, Mary T [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 28.06.2022 Date Revised 13.07.2023 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.jlr.2022.100224 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 100 | 1 | |a Doan, Mary T |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Direct anabolic metabolism of three-carbon propionate to a six-carbon metabolite occurs in vivo across tissues and species |
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| 500 | |a Date Revised 13.07.2023 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved. | ||
| 520 | |a Anabolic 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 | ||
| 650 | 4 | |a Journal Article | |
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| 650 | 4 | |a Metabolism | |
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| 650 | 4 | |a acetyl-CoA | |
| 650 | 4 | |a anabolism | |
| 650 | 4 | |a condensation reaction | |
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| 700 | 1 | |a Varner, Erika L |e verfasserin |4 aut | |
| 700 | 1 | |a Bedi, Kenneth C |c Jr |e verfasserin |4 aut | |
| 700 | 1 | |a Bartee, David |e verfasserin |4 aut | |
| 700 | 1 | |a Jiang, Helen |e verfasserin |4 aut | |
| 700 | 1 | |a Trefely, Sophie |e verfasserin |4 aut | |
| 700 | 1 | |a Xu, Peining |e verfasserin |4 aut | |
| 700 | 1 | |a Singh, Jay P |e verfasserin |4 aut | |
| 700 | 1 | |a Jang, Cholsoon |e verfasserin |4 aut | |
| 700 | 1 | |a Rame, J Eduardo |e verfasserin |4 aut | |
| 700 | 1 | |a Brady, Donita C |e verfasserin |4 aut | |
| 700 | 1 | |a Meier, Jordan L |e verfasserin |4 aut | |
| 700 | 1 | |a Marguiles, Kenneth B |e verfasserin |4 aut | |
| 700 | 1 | |a Arany, Zoltan |e verfasserin |4 aut | |
| 700 | 1 | |a Snyder, Nathaniel W |e verfasserin |4 aut | |
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