Pyruvate Dehydrogenase Acetyl-Transferring Kinase

A pyruvate dehydrogenase kinase isozyme located in the mitochondria which converts PYRUVATE to ACETYL CoA in the CITRIC ACID CYCLE, phosphorylates SERINE residues on pyruvate dehydrogenase using ATP, and plays a key role in the regulation of GLUCOSE and fatty acid metabolism.

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Networked: 404 relevant articles (5 outcomes, 31 trials/studies)

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Bio-Agent Context: Research Results

Experts

1.	Harris, Robert A: 9 articles (01/2021 - 08/2006)
2.	Lee, In-Kyu: 9 articles (01/2021 - 06/2014)
3.	Chung, Tae-Wook: 7 articles (12/2020 - 12/2011)
4.	Jha, Mithilesh Kumar: 6 articles (11/2020 - 10/2013)
5.	Suk, Kyoungho: 6 articles (11/2020 - 10/2013)
6.	Archer, Stephen L: 6 articles (01/2020 - 01/2007)
7.	Hu, Xiaohui: 6 articles (11/2018 - 04/2016)
8.	Tam, Kin Yip: 6 articles (11/2018 - 04/2016)
9.	Michelakis, Evangelos D: 6 articles (10/2017 - 01/2007)
10.	Lopaschuk, Gary D: 6 articles (04/2013 - 01/2007)

Related Diseases

1.	Neoplasms (Cancer) 01/01/2017 - "Dichloroacetate, a controversially discussed subject of many studies in cancer research, is a pyruvate dehydrogenase kinase inhibitor. " 01/01/2017 - "In this study, the pyruvate dehydrogenase kinase (PDK)4 gene was shown to have potential tumor suppressor characteristics. " 09/13/2016 - "Recently, several studies have suggested that dichloroacetate (DCA), a specific pyruvate dehydrogenase kinase inhibitor, may be a potential anticancer drug in a large number of diverse tumors. " 01/01/2015 - "Therefore, the purpose of this study was to shift tumor cells from aerobic glycolysis to oxidative phosphorylation using dichloroacetate (DCA), an inhibitor of PDH-kinase. " 01/01/2023 - "Pyruvate dehydrogenase kinase 1 (PDK1) plays an important role in regulating the metabolic reprogramming of cancer cells. "
2.	Insulin Resistance 02/24/2015 - "Perpetual muscle PDH activation in PDH kinase knockout mice protects against high-fat feeding-induced muscle insulin resistance." 01/01/1995 - "This long-term enhancement of PDH kinase activity is concomitant with the development of whole-body insulin resistance and adds a new dimension to the potential role of dietary composition in the pathogenesis of insulin resistance." 12/01/2022 - "Inhibition of pyruvate dehydrogenase kinase improves carbohydrate utilization in Nile tilapia by regulating PDK2/4-PDHE1α axis and insulin sensitivity." 05/31/1996 - "The results demonstrate a direct hepatic action of T3 to increase PDH kinase activity, which is mediated by intramitochondrial fatty acyl-CoA or a product of beta-oxidation, and facilitated by hepatic insulin resistance." 12/01/2015 - "We hypothesized that the so far poorly understood improvement in postoperative insulin sensitivity, when surgery is preceded by a carbohydrate (CHO) drink, occurs via attenuation of skeletal muscle inflammatory responses to surgery, improved insulin signaling and attenuated expression of muscle pyruvate dehydrogenase kinase (PDK) 4. Vastus lateralis muscle biopsies, collected before and after major abdominal surgery and during postoperative hyperinsulinaemic-euglycaemic clamping from 16 pigs randomized to either 200 ml of a CHO-supplemented drink 2 h before surgery (CHO, 25 g; n = 8), or preoperative overnight fasting (fasted; n = 8), were analyzed by fast qRT-PCR and IR-Western blotting. "
3.	Type 2 Diabetes Mellitus (MODY) 02/01/2022 - "Dichloroacetate, a pyruvate dehydrogenase kinase inhibitor, ameliorates type 2 diabetes via reduced gluconeogenesis." 01/01/2023 - "Our analysis highlights multiple targets of pyruvate dehydrogenase kinase 1 (PDK1), a regulator of mitochondrial function that shows reduced activity in the NZO/HILtJ mouse, a polygenic model of obesity and type 2 diabetes. " 12/01/2003 - "AZD7545 is one of a series of PDH kinase inhibitors developed for the treatment of type 2 diabetes. " 09/25/2009 - "The hypothesis that PDHK4 (pyruvate dehydrogenase kinase isoenzyme 4) has potential as a target for the treatment of type 2 diabetes was tested by feeding wild-type and PDHK4 knockout mice a high saturated fat diet that induces hyperglycemia, hyperinsulinaemia, glucose intolerance, hepatic steatosis and obesity. " 09/12/2008 - "Human pyruvate dehydrogenase complex (PDC) is down-regulated by pyruvate dehydrogenase kinase (PDK) isoforms 1-4. PDK4 is overexpressed in skeletal muscle in type 2 diabetes, resulting in impaired glucose utilization. "
4.	Hypoxia (Hypoxemia) 01/01/2019 - "PDH kinase 1, highly expressed under hypoxia, is down-regulated under normoxic conditions, leading to an increase in dephosphorylated PDH. " 01/01/2019 - "Induction of Pyruvate Dehydrogenase Kinase 1 by Hypoxia Alters Cellular Metabolism and Inhibits Apoptosis in Endometriotic Stromal Cells." 10/01/2017 - "Treatment with dichloroacetate (DCA), an inhibitor of pyruvate dehydrogenase kinase (PDK), induced cell death in GBM28 and GBM37 maintained under normoxia, whereas DCA effects disappeared under hypoxia, suggesting that hypoxic adaptation dominated DCA effects in these GBMs. " 01/01/2016 - "Muscle fiber-type changes in hypoxic conditions in accordance with pyruvate dehydrogenase kinase (Pdk)-1 and hypoxia inducible factor (Hif)-1α were investigated in rats. " 09/01/2014 - "Mechanistically, HIF activity, but not hypoxia per se is found to be necessary and sufficient to increase exon inclusion of several HIF targets, including pyruvate dehydrogenase kinase 1 (PDK1). "
5.	Starvation 07/01/2004 - "Starvation and experimental diabetes induce a stable increase in pyruvate dehydrogenase kinase (PDK) activity in skeletal muscle, which is largely due to a selective upregulation of PDK-4 expression. " 09/01/2000 - "Starvation increases the amount of pyruvate dehydrogenase kinase in several mammalian tissues." 08/01/1999 - "Starvation and diabetes induce a stable increase in pyruvate dehydrogenase kinase activity in skeletal muscle mitochondria that promotes phosphorylation and inactivation of the complex. " 06/01/1999 - "Estimations of PDH kinase (PDK) activity in renal mitochondria showed a significant 1.7-fold stable increase (P < .01) after 48 hours of starvation. " 06/07/1996 - "Starvation for 24 h in rats previously maintained on standard diet also evoked a substantial increase in hepatic pyruvate dehydrogenase kinase activity. "

Related Drugs and Biologics

1.	Lactate Dehydrogenase 5
2.	Proteins (Proteins, Gene)
3.	Glucose (Dextrose)
4.	Hexokinase
5.	Enzymes
6.	Facilitative Glucose Transport Proteins (Glucose Transporter)
7.	Pyruvate Kinase
8.	Messenger RNA (mRNA)
9.	Insulin (Novolin)
10.	Glutaminase

Related Therapies and Procedures

1.	Drug Therapy (Chemotherapy)
2.	Radiotherapy
3.	Therapeutics
4.	Ligation
5.	Intraperitoneal Injections