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Ins and Outs of the TCA Cycle: The Central Role of Anaplerosis
Abstract
The reactions of the tricarboxylic acid (TCA) cycle allow the controlled combustion of fat and carbohydrate. In principle, TCA cycle intermediates are regenerated on every turn and can facilitate the oxidation of an infinite number of nutrient molecules. However, TCA cycle intermediates can be lost to cataplerotic pathways that provide precursors for biosynthesis, and they must be replaced by anaplerotic pathways that regenerate these intermediates. Together, anaplerosis and cataplerosis help regulate rates of biosynthesis by dictating precursor supply, and they play underappreciated roles in catabolism and cellular energy status. They facilitate recycling pathways and nitrogen trafficking necessary for catabolism, and they influence redox state and oxidative capacity by altering TCA cycle intermediate concentrations. These functions vary widely by tissue and play emerging roles in disease. This article reviews the roles of anaplerosis and cataplerosis in various tissues and discusses how they alter carbon transitions, and highlights their contribution to mechanisms of disease.
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“However, several chemical intermediates of the TCA cycle also serve as critical precursors for biosynthetic reactions, which we will discuss in detail later (5, 6).”
From Regulation and function of the mammalian tricarboxylic acid cycle (2023) · cites this paper as [5]
In the citing paper
“Rather, propionyl-CoA is converted to the TCA cycle intermediate succinyl-CoA through a pathway involving propionyl-CoA carboxylase and methylmalonyl-CoA mutase (5).”
From Regulation and function of the mammalian tricarboxylic acid cycle (2023) · cites this paper as [5]
In the citing paper
“A similar alternative entry point for amino acids into the TCA cycle is direct conversion of phenylalanine and tyrosine to fumarate by fumarylacetoacetate hydratase (5).”
From Regulation and function of the mammalian tricarboxylic acid cycle (2023) · cites this paper as [5]
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Metadata
- Authors
- Inigo, M., Deja, S., & Burgess, S. C.
- Affiliations
- Center for Human Nutrition, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA;
- The University of Texas Southwestern Medical Center (US)
- Venue
- Annual Review of Nutrition
- Publisher
- Annual Reviews
- Published
- 2021-10-11
- Volume
- 41
- Issue
- 1
- Pages
- 19-47
- ISSN
- 0199-9885 (ISSN-L)
- 1545-4312
- OpenAlex
- W3178058019
- Cited by
- 189
- References
- 150
- Citations by year
- 2026: 48 · 2025: 56 · 2024: 35 · 2023: 33 · 2022: 15 · 2021: 2
- FWCI
- 2.15
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Annual Review of Nutrition (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK128168, R01DK078184)
- National Institute of Biomedical Imaging and Bioengineering (P41EB015908)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Biochemical Acid Research Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Keywords
- TCA cycle, anaplerosis, cataplerosis, TCA cycle intermediates, biosynthetic precursors, catabolism, cellular energy status, redox state, oxidative capacity, tissue-specific metabolism, disease mechanisms
- MeSH terms
- Citric Acid Cycle, Humans, Oxidation-Reduction
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