Regulation of mammalian pyruvate dehydrogenase

@article{Denton2005RegulationOM,
  title={Regulation of mammalian pyruvate dehydrogenase},
  author={Richard M. Denton and Philip J. Randle and Barbara J. Bridges and Ronald H. Cooper and Alan L. Kerbey and H. T. Pask and David L. Severson and David Stansbie and Susan Whitehouse},
  journal={Molecular and Cellular Biochemistry},
  year={2005},
  volume={9},
  pages={27-53}
}
SummaryIn mammalian tissues, two types of regulation of the pyruvate dehydrogenase complex have been described: end product inhibition by acetyl CoA and NADH; and the interconversion of an inactive phosphorylated form and an active non-phosphorylated form by an ATP requiring kinase and a specific phosphatase.This article is largely concerned with the latter type of regulation of the complex in adipose tissue by insulin (and other hormones) and in heart muscle by lipid fuels. Effectors of the… Expand
Ions and the Output of Acetylcoenzyme A from Brain Mitochondria
Purified rat brain mitochondria were incubated in the presence of pyruvate or (lC)pyruvate and the output of the pyruvate-generated acetylcoen­ zyme A (acetyl-CoA) from the mitochondria into theExpand
Human Skeletal Muscle Pyruvate Dehydrogenase Phosphatase Activity and Expression: The Effect of Aerobic Capacity
TLDR
The data suggest that with increased aerobic capacity there is an increased capacity for carbohydrate oxidation through PDH, via El a, and an increased ability to activate PDP, via PDP, when exercising maximally. Expand
The mitochondrial isoform of phosphoenolpyruvate carboxykinase (PEPCK-M) and glucose homeostasis: has it been overlooked?
TLDR
It is proposed that PEPCK-M, as a sensor for TCA cycle flux, is a key mechanism to regulate both insulin secretion and gluconeogenesis suggesting conservation of this biochemical mechanism in regulating multiple aspects of glucose homeostasis. Expand
The effect of glucose on cardiac AMP-activated protein kinase
AMP-activated protein kinase (AMPK) serves as an energy-sensing protein that is activated by a variety of metabolic stresses. Recent studies suggest that AMPK is also regulated by hormones and byExpand
Calcium-sensitive pyruvate dehydrogenase phosphatase is required for energy metabolism, growth, differentiation, and infectivity of Trypanosoma cruzi
TLDR
TcPDP is a Ca2+-stimulated mitochondrial phosphatase that dephosphorylates TcPDH and is required for normal growth, differentiation, infectivity, and energy metabolism in T. cruzi. Expand
Anti-insulin receptor antibodies mimic the effects of insulin on the activities of pyruvate dehydrogenase and acetylCoA carboxylase and on specific protein phosphorylation in rat epididymal fat cells
TLDR
Findings lend further support to the view that the short term effects of insulin do not involve the entry of the insulin molecule (or part thereof) into cells of target tissues. Expand
Signaling at the gate: Phosphorylation of the mitochondrial protein import machinery
TLDR
The current model of protein import regulation, together with additional mitochondrial functions of CK2 and PKA, is outlined and reflects the data on mitochondria-associated protein kinases and phosphatases in the model organism baker's yeast. Expand
Expression of pyruvate dehydrogenase kinase-1 in gastric cancer as a potential therapeutic target
TLDR
PDK- 1 may serve as a biomarker of poor prognosis in patients with gastric cancer and PDK-1 inhibitors such as DCA may be considered an additional treatment option for patients with PDK -1-expressing gastric cancers. Expand
Involvement of Calcium in Calcitonin Induced Stimulation of Glycolysis in Rat Kidney in situ
The effects of intravenous salmon calcitonin on tissue carbohydrate and redox metabolism were studied in rat kidney in situ and were compared to the effects of EGTA infusion. Calcitonin (0.8 MRC U,Expand
The mitochondrial proteome: A dynamic functional program in tissues and disease states
  • R. Balaban
  • Biology, Medicine
  • Environmental and molecular mutagenesis
  • 2010
TLDR
Screening methods are being introduced to detect the active or dynamic posttranslational sites to focus attention on sites that might provide insight into regulatory mechanisms, including kinase and phosphatase regulatory network. Expand
...
1
2
3
4
5
...

References

SHOWING 1-10 OF 91 REFERENCES
Regulation of pyruvate dehydrogenase in rat liver mitochondria by phosphorylation-dephosphorylation.
TLDR
It is concluded that the normal content of Mg2+ and Ca2+ in isolated mitochondria is sufficient to provide optimal activation of pyruvate dehydrogenase phosphatase and that release of M gATP2- to ADP, Pi, and M g2+ during active respiration has a negligible effect on pyruVate dehydrogensaseosphatase activity. Expand
Alpha-keto acid dehydrogenase complexes. XI. Comparative studies of regulatory properties of the pyruvate dehydrogenase complexes from kidney, heart, and liver mitochondria.
The activity of the multienzyme pyruvate dehydrogenase complexes, isolated from mitochondria of beef kidney, beef heart, and pork liver, is regulated by phosphorylation and dephosphorylation.Expand
Alpha-keto acid dehydrogenase complexes. X. Regulation of the activity of the pyruvate dehydrogenase complex from beef kidney mitochondria by phosphorylation and dephosphorylation.
  • T. Linn, F. Pettit, L. Reed
  • Chemistry, Medicine
  • Proceedings of the National Academy of Sciences of the United States of America
  • 1969
This paper reports the discovery that the activity of the multienzyme pyruvate dehydrogenase complex from beef kidney mitochondria is regulated by a phosphorylation-dephosphorylation reactionExpand
Function of calcium ions in pyruvate dehydrogenase phosphatase activity.
TLDR
Evidence is presented that the activity of the PDH phosphatase from bovine kidney and heart is increased about tenfold when it is attached to the transacetylase, which could provide an important mechanism for regulation of the phosphorylation-dephosphorylation cycle. Expand
Interconversion of phospho- and dephospho- forms of pig heart pyruvate dehydrogenase.
  • O. Wieland, E. Siess
  • Chemistry, Medicine
  • Proceedings of the National Academy of Sciences of the United States of America
  • 1970
TLDR
The participation of this phosphate in the pyruvate dehydrogenase interconversion system suggests that, in heart muscle, pyruVate oxidation may be under hormonal control by a mechanism similar to that involved in the regulation of glycogen synthesis and breakdown. Expand
Alpha-keto acid dehydrogenase complexes. XX. A kinetic study of the pyruvate dehydrogenase complex from bovine kidney.
TLDR
Evidence is presented which suggests that these anomalous product inhibition patterns are due to physical association of the flavoprotein with the transacetylase so that combination of acetyl-CoA with thetransacetyl enzyme hinders combination of NAD with the Flavoprotein and combination of NadH with the flavo-NAD, which is consistent with the patterns predicted from rate equations derived by Cleland for three-site ping-pong mechanisms. Expand
Regulation of pyruvate dehydrogenase in mitochondria of rat liver.
TLDR
These studies lend support to the view that, in liver, the state of the pyruvate dehydrogenase system is under metabolic control and that ADP may thereby play an essential role. Expand
Regulation of heart muscle pyruvate dehydrogenase kinase.
TLDR
It is suggested that acetoin formation may contribute to activation of the kinase reaction by low pyruvate concentrations in the presence of thiamin pyrophosphate, and that ADP and adenylyl imidodiphosphate inhibit the Kinase mainly by binding to the ATP site and that the adenosine moiety may be involved in this binding. Expand
Mechanisms regulating adipose-tissue pyruvate dehydrogenase.
TLDR
It is concluded that the activation of pyruvate dehydrogenase by insulin is not due to the antilipolytic effect of the hormone and that the action of insulin in lowering adipose-cell concentrations of cyclic AMP does not afford an obvious explanation for the effect ofthe hormone. Expand
Pyruvate dehydrogenase, substrate specificity and product inhibition.
1 Studies with intact mitochondria and with soluble pyruvate dehydrogenase indicate that pyruvate and α-ketobutyrate are oxidized by the same enzyme (pyruvate dehydrogenase), while α-ketovalerate isExpand
...
1
2
3
4
5
...