Pyruvate dehydrogenase kinases (PDKs): an overview toward clinical applications

• Published in: Bioscience reports Vol. 41; no. 4
• Main Authors: Wang, Xiuxiu, Shen, Xiaoyue, Yan, Yuting, Li, Hongmin
• Format: Journal Article
• Language: English
• Published: England Portland Press Ltd The Biochemical Society 30.04.2021; Portland Press Ltd
• Subjects: Animals; Apoptosis; Binding sites; Biotechnology; Cancer; Cardiovascular Diseases - metabolism; Catalytic activity; Chemical Biology; Congestive heart failure; Decarboxylation; Dehydrogenase; Dehydrogenases; Diabetes; Diabetes mellitus; Diabetes Mellitus - metabolism; Energy metabolism; Enzymes; Enzymology; Fatty acids; Genes; Glucose; Glycolysis; Heart; Heart diseases; Hormones; Humans; Hypoxia; Injury prevention; Insulin; Ischemia; Kinases; Liver; Metabolic disorders; Metabolism; Metabolites; Mitochondria; Musculoskeletal system; Myocardial ischemia; Neoplasms - metabolism; Oxidation; Phosphatase; Phosphorylation; Protein Engineering; Pyruvate dehydrogenase (lipoamide); Pyruvate Dehydrogenase Complex - antagonists & inhibitors; Pyruvate Dehydrogenase Complex - genetics; Pyruvate Dehydrogenase Complex - metabolism; Pyruvic acid; R&D; Research & development; Review; Transcription factors; Tricarboxylic acid cycle; Tumor cells; pyruvate dehydrogenase complex; pyruvate; pyruvate dehydrogenase kinase
• ISSN: 0144-8463; 1573-4935; 1573-4935
• DOI: 10.1042/BSR20204402

Pyruvate dehydrogenase kinase (PDK) can regulate the catalytic activity of pyruvate decarboxylation oxidation via the mitochondrial pyruvate dehydrogenase complex, and it further links glycolysis with the tricarboxylic acid cycle and ATP generation. This review seeks to elucidate the regulation of PDK activity in different species, mainly mammals, and the role of PDK inhibitors in preventing increased blood glucose, reducing injury caused by myocardial ischemia, and inducing apoptosis of tumor cells. Regulations of PDKs expression or activity represent a very promising approach for treatment of metabolic diseases including diabetes, heart failure, and cancer. The future research and development could be more focused on the biochemical understanding of the diseases, which would help understand the cellular energy metabolism and its regulation by pharmacological effectors of PDKs.