Integration of Adenylate Kinase and Glycolytic and Glycogenolytic Circuits in Cellular Energetics

Research output: Chapter in Book/Report/Conference proceedingChapter

31 Citations (Scopus)

Abstract

Emerging evidence indicates that adenylate kinase and glycolytic/glycogenolytic phosphotransfer enzyme circuits are essential parts of cardiac system bioenergetics, playing a significant role in muscle energetics by delivering high-energy phosphoryls and conveying energy demand signals to ATP-generating pathways and metabolic sensors. Adenylate kinase phosphotransfer promptly respondsto metabolic imbalances, facilitating transfer and utilization of both g-and bphosphoryls of the ATP molecule and maintaining energy economy. Adenylate kinase-mediated intracellular AMP signaling coupled with AMP-responsive elements such as AMP-sensitive protein kinase (AMPK), ATP-sensitive potassium channels (KATP), and AMP-sensitive metabolic enzymes, along with adenosine signaling, comprise a key metabolic sensing system regulating vital cellular processes. Localized in close proximity to metabolic sensors, adenylate kinase-catalyzed AMP signal generation and nucleotide exchange regulate the dynamics and frequency of ligand switching in the intimate sensing zone, facilitating the decoding of cellular information. By instigating AMP signaling, adenylate kinase regulates the activity of glycolytic and glycogenolytic enzymes and provides an integrative node for bioenergetic pathways to respond with high fidelity to increased energy demand. Genetic deficiency of the cytosolic AK1 isoform results in defective muscle energetics and AMP signaling, compromising the response to metabolic stress. Spatial extension of the glycolytic pathway indicates that it comprises a network of phosphotransfer circuits and metabolite shuttles, which facilitate high-energy phosphoryl delivery and lactate/pyruvate and Pi shuttling and thus maintain cellular energy and redox balance. The dynamics of glycogen utilization and synthesis, processes that occur close to myofibrillar and mitochondrial compartments, also suggest the existence of a glycogenolytic energetic circuit. In the proposed glycogen energetic network model, mitochondrial metabolic energy, invested into glycogen through locally generated UTP and G-6-P/G-1-P, is released during glycogenolysis at ATP utilization sites in myofibrils and other cellular compartments. Thus, systemic integration of different energetic and metabolic signaling pathways ensures cellular energy homeostasis and an adequate response to a broad range of functional activities and stress challenges.

Original languageEnglish (US)
Title of host publicationMolecular System Bioenergetics: Energy for Life
PublisherWiley-VCH Verlag GmbH & Co. KGaA
Pages265-301
Number of pages37
ISBN (Print)9783527317875
DOIs
StatePublished - Nov 22 2007

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Adenylate Kinase
Adenosine Monophosphate
Networks (circuits)
Glycogen
Adenosine Triphosphate
Metabolic Networks and Pathways
Energy Metabolism
Muscle
Enzymes
Glycogenolysis
Muscles
KATP Channels
Uridine Triphosphate
Physiological Stress
Myofibrils
Sensors
Conveying
Metabolites
Pyruvic Acid
Adenosine

Keywords

  • Adenylate kinase
  • AMP metabolic signaling
  • Energy transfer networks
  • Glycogenolytic circuits
  • Glycolytic circuits
  • Metabolic feedback regulation
  • Metabolite shuttles
  • Modeling cellular energetics
  • Molecular system bioenergetics
  • Phosphotransfer circuits

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Dzeja, P. P., Chung, S., & Terzic, A. (2007). Integration of Adenylate Kinase and Glycolytic and Glycogenolytic Circuits in Cellular Energetics. In Molecular System Bioenergetics: Energy for Life (pp. 265-301). Wiley-VCH Verlag GmbH & Co. KGaA. https://doi.org/10.1002/9783527621095.ch8

Integration of Adenylate Kinase and Glycolytic and Glycogenolytic Circuits in Cellular Energetics. / Dzeja, Petras P; Chung, Susan; Terzic, Andre.

Molecular System Bioenergetics: Energy for Life. Wiley-VCH Verlag GmbH & Co. KGaA, 2007. p. 265-301.

Research output: Chapter in Book/Report/Conference proceedingChapter

Dzeja, PP, Chung, S & Terzic, A 2007, Integration of Adenylate Kinase and Glycolytic and Glycogenolytic Circuits in Cellular Energetics. in Molecular System Bioenergetics: Energy for Life. Wiley-VCH Verlag GmbH & Co. KGaA, pp. 265-301. https://doi.org/10.1002/9783527621095.ch8
Dzeja PP, Chung S, Terzic A. Integration of Adenylate Kinase and Glycolytic and Glycogenolytic Circuits in Cellular Energetics. In Molecular System Bioenergetics: Energy for Life. Wiley-VCH Verlag GmbH & Co. KGaA. 2007. p. 265-301 https://doi.org/10.1002/9783527621095.ch8
Dzeja, Petras P ; Chung, Susan ; Terzic, Andre. / Integration of Adenylate Kinase and Glycolytic and Glycogenolytic Circuits in Cellular Energetics. Molecular System Bioenergetics: Energy for Life. Wiley-VCH Verlag GmbH & Co. KGaA, 2007. pp. 265-301
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