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

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 P...

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Published inBioscience reports Vol. 41; no. 4
Main Authors Wang, Xiuxiu, Shen, Xiaoyue, Yan, Yuting, Li, Hongmin
Format Journal Article
LanguageEnglish
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
Online AccessGet full text
ISSN0144-8463
1573-4935
1573-4935
DOI10.1042/BSR20204402

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Abstract 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.
AbstractList 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.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.
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.
Author Yan, Yuting
Shen, Xiaoyue
Wang, Xiuxiu
Li, Hongmin
AuthorAffiliation 1 Provincial Key Laboratory of Biotechnology of Shaanxi, College of Life Sciences, Northwest University, Taibai North Rd 229, Xi’an, Shaanxi Province 710069, China
2 Key Laboratory of Resource Biology and Biotechnology in Western China, Ministry of China, Taibai North Rd 229, Xi'an, Shaanxi Province 710069, China
AuthorAffiliation_xml – name: 2 Key Laboratory of Resource Biology and Biotechnology in Western China, Ministry of China, Taibai North Rd 229, Xi'an, Shaanxi Province 710069, China
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  organization: Provincial Key Laboratory of Biotechnology of Shaanxi, College of Life Sciences, Northwest University, Taibai North Rd 229, Xi’an, Shaanxi Province 710069, China, Key Laboratory of Resource Biology and Biotechnology in Western China, Ministry of China, Taibai North Rd 229, Xi'an, Shaanxi Province 710069, China
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Issue 4
Keywords pyruvate dehydrogenase complex
pyruvate
pyruvate dehydrogenase kinase
Language English
License 2021 The Author(s).
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crossref_citationtrail_10_1042_BSR20204402
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PublicationDate 2021-04-30
PublicationDateYYYYMMDD 2021-04-30
PublicationDate_xml – month: 04
  year: 2021
  text: 2021-04-30
  day: 30
PublicationDecade 2020
PublicationPlace England
PublicationPlace_xml – name: England
– name: New York
PublicationTitle Bioscience reports
PublicationTitleAlternate Biosci Rep
PublicationYear 2021
Publisher Portland Press Ltd The Biochemical Society
Portland Press Ltd
Publisher_xml – name: Portland Press Ltd The Biochemical Society
– name: Portland Press Ltd
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  article-title: Cloning of the rat pyruvate dehydrogenase kinase 4 gene promoter: activation of pyruvate dehydrogenase kinase 4 by the peroxisome proliferator-activated receptor gamma coactivator
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  article-title: Pyruvate dehydrogenase kinase 1 and carbonic anhydrase IX targeting in hypoxic tumors
  publication-title: Neoplasma
  doi: 10.4149/neo_2018_180531N357
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Snippet Pyruvate dehydrogenase kinase (PDK) can regulate the catalytic activity of pyruvate decarboxylation oxidation via the mitochondrial pyruvate dehydrogenase...
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SubjectTerms 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
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  providerName: ProQuest
Title Pyruvate dehydrogenase kinases (PDKs): an overview toward clinical applications
URI https://www.ncbi.nlm.nih.gov/pubmed/33739396
https://www.proquest.com/docview/2957191456
https://www.proquest.com/docview/2503435382
https://pubmed.ncbi.nlm.nih.gov/PMC8026821
Volume 41
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