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Wilson, D. F. (2015). Programming and regulation of metabolic homeostasis. American Journal of Physiology-Endocrinology and Metabolism. Added by: Dr. Enrique Feoli (15/02/2021, 22:10) Last edited by: Dr. Enrique Feoli (18/02/2021, 01:37) |
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| Resource type: Journal Article BibTeX citation key: Wilson2015 View all bibliographic details  |
Categories: BioAcyl Corp, BioAcyl Corp Subcategories: Adenylate energy system, Metabolic signaling Creators: Wilson Collection: American Journal of Physiology-Endocrinology and Metabolism |
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| Abstract |
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Evidence is presented that the rate and equilibrium constants in mitochondrial oxidative phosphorylation set and maintain metabolic homeostasis in eukaryotic cells. These internal constants determine the energy state ([ATP]/[ADP][Pi]), and the energy state maintains homeostasis through a bidirectional sensory/signaling control network that reaches every aspect of cellular metabolism. The energy state is maintained with high precision (to ∼1 part in 1010), and the control system can respond to transient changes in energy demand (ATP utilization) of more than 100 times the resting rate. Epigenetic and environmental factors are able to “fine-tune” the programmed set point over a narrow range to meet the special needs associated with cell differentiation and chronic changes in metabolic requirements. The result is robust across-platform control of metabolism, which is essential to cellular differentiation and the evolution of complex organisms. A model of oxidative phosphorylation is presented, for which the steady-state rate expression has been derived and computer programmed. The behavior of oxidative phosphorylation predicted by the model is shown to fit the experimental data available for isolated mitochondria as well as for cells and tissues. This includes measurements from several different mammalian tissues as well as from insect flight muscle and plants. The respiratory chain and oxidative phosphorylation is remarkably similar for all higher plants and animals. This is consistent with the efficient synthesis of ATP and precise control of metabolic homeostasis provided by oxidative phosphorylation being a key to cellular differentiation and the evolution of structures with specialized function.
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| Notes |
 A schematic of the role of oxidative phosphorylation in setting and maintaining metabolic homeostasis. This is a minimal schematic showing some of the bidirectional signaling/control functions of the energy state. All cellular and tissue metabolism is coupled to and regulated by energy state. Of the thousands of control pathways that exist, only a few related to major metabolic and growth processes are indicated and then without any detail. Readers can easily fill in the control pathways to any particular cellular metabolic pathway or process. CAC, citric acid cycle.
In the current paper, evidence that oxidative phosphorylation is responsible for setting and regulating metabolic homeostasis in higher organisms will be further developed. Cytochrome c oxidase activity determines the rate of ATP synthesis by mitochondria (10, 31, 66–70, 74, 76), and a model consistent with the dependence of the rate of oxygen reduction on cytochrome c reduction, energy state, pH, and oxygen pressure has been published (76). However, in vivo, the primary source of reducing equivalents is NADH generated by the citric acid cycle, fatty acid oxidation, and amino acid catabolism. To integrate the control of cytochrome c oxidase into cellular energy metabolism as a whole, the model for cytochrome c oxidase is extended to include the first two sites of oxidative phosphorylation, coupling it to the intramitochondrial NAD pool. The result is a model that is consistent with currently available information of the dependence of energy metabolism on the intramitochondrial NAD pool, Po2, pH, and energy state. |