PDK2: An Underappreciated Regulator of Liver Metabolism
Abstract
:1. Introduction
2. The PDKs and PDH
3. Physiological Roles of PDKs
3.1. PDKs in Normal Physiology
3.2. Specific Roles for PDK2 in Normal Physiology:
4. Transcriptional Regulators of PDK2 Expression
5. PDK2 Inhibitors
5.1. Dichloroacetate
5.2. ATP Binding Site/PS10
5.3. Lipoyl-Binding Domain/AZD7545
6. Pathophysiological Roles of PDKs in Disease
6.1. PDK2 and the Metabolic Syndrome
PDK2 and Nutrient Excess
6.2. PDK2 in Cancer
PDK2 in Hepatocellular Carcinoma
7. PDKs in Inflammation, a Growing Area of Interest
8. Conclusions
Author Contributions
Funding
Conflicts of Interest
References
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Inhibitor | Target | Efficacy | Notes | Refs |
---|---|---|---|---|
Dichloroacetate | pyruvate binding site | millimolar | common inhibitor | [4] |
PS10 | ATP binding site | micromolar | high specificity for PDKs 2 and 4, and to a lesser degree PDK1 | [36] |
azd7545 | PDH E2 lipoyl domain | micromolar | higher specificity for PDK1 and PDK2 | [37,38] |
2-chloropropionate | pyruvate binding site | millimolar | DCA analog | [4] |
radicicol | ATP binding site | micromolar | also inhibits HSP90 | [39] |
VER-246608 | ATP binding site | millimolar | pan-isoform inhibitor | [40] |
Compound 17, PS10 derivative | ATP binding site inhibitor | micromolar | poorly defined thus far | [36,41] |
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Woolbright, B.L.; Harris, R.A. PDK2: An Underappreciated Regulator of Liver Metabolism. Livers 2021, 1, 82-97. https://doi.org/10.3390/livers1020008
Woolbright BL, Harris RA. PDK2: An Underappreciated Regulator of Liver Metabolism. Livers. 2021; 1(2):82-97. https://doi.org/10.3390/livers1020008
Chicago/Turabian StyleWoolbright, Benjamin L., and Robert A. Harris. 2021. "PDK2: An Underappreciated Regulator of Liver Metabolism" Livers 1, no. 2: 82-97. https://doi.org/10.3390/livers1020008