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The pivotal role of pyruvate dehydrogenase kinases in metabolic flexibility
Open accessAbstract
Metabolic flexibility is the capacity of a system to adjust fuel (primarily glucose and fatty acids) oxidation based on nutrient availability. The ability to alter substrate oxidation in response to nutritional state depends on the genetically influenced balance between oxidation and storage capacities. Competition between fatty acids and glucose for oxidation occurs at the level of the pyruvate dehydrogenase complex (PDC). The PDC is normally active in most tissues in the fed state, and suppressing PDC activity by pyruvate dehydrogenase (PDH) kinase (PDK) is crucial to maintain energy homeostasis under some extreme nutritional conditions in mammals. Conversely, inappropriate suppression of PDC activity might promote the development of metabolic diseases. This review summarizes PDKs' pivotal role in control of metabolic flexibility under various nutrient conditions and in different tissues, with emphasis on the best characterized PDK4. Understanding the regulation of PDC and PDKs and their roles in energy homeostasis could be beneficial to alleviate metabolic inflexibility and to provide possible therapies for metabolic diseases, including type 2 diabetes (T2D).
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“competition between fatty acids and glucose occurs at the level of the pyruvate dehydrogenase complex”
From Metabolic Flexibility as an Adaptation to Energy Resources and Requirements in Health and Disease (2018) · cites this paper as [314]
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Metadata
- Authors
- Zhang, S., Hulver, M. W., McMillan, R. P., Cline, M. A., & Gilbert, E. R.
- Affiliations
- Virginia Tech (US)
- Corresponding author
- Gilbert, Elizabeth R
- Venue
- Nutrition & Metabolism
- Published
- 2014-02-12
- Volume
- 11
- Issue
- 1
- Pages
- 10-10
- ISSN
- 1743-7075 (ISSN-L)
- PMC
- PMC3925357
- OpenAlex
- W2170096200
- Cited by
- 450
- References
- 78
- Citations by year
- 2026: 19 · 2025: 43 · 2024: 34 · 2023: 70 · 2022: 45 · 2021: 39 · 2020: 55 · 2019: 38 · 2018: 40 · 2017: 23 · 2016: 20 · 2015: 18 · 2014: 5
- FWCI
- 9.79
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by
- Locations
- Nutrition & Metabolism (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- VTechWorks (Virginia Tech) (submittedVersion, cc-by)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Biochemical Acid Research Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Health Sciences › Medicine › Physiology (medical) › Adipose Tissue and Metabolism
- Keywords
- pyruvate dehydrogenase kinase, pyruvate dehydrogenase complex, metabolic flexibility, PDK4, energy homeostasis, glucose oxidation, fatty acid oxidation, substrate competition, metabolic inflexibility, type 2 diabetes, metabolic disorders
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