Role of cellular compartmentation in the metabolic response to stress: mechanistic insights from computational models.

Role of cellular compartmentation in the metabolic response to stress: mechanistic insights from computational models. Research Abstract Details 

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Role of cellular compartmentation in the metabolic response to stress: mechanistic insights from computational models. Abstract Text:

Lufang Zhou,Xin Yu,Marco E Cabrera,William C Stanley,

The mechanisms controlling ATP generation in the transition from normal resting conditions to either high work states or ischemia are poorly understood. ATP generation depends upon compartmentation between the mitochondria and cytosol of metabolic pathways and key energy transfer species that cannot be easily assessed experimentally. We developed a multicompartment mathematical model of cardiac metabolism to simulate the metabolic responses to ischemia and increased workload. The model is based on mass balances, transport, and metabolic processes in cardiac tissue, and has three distinct compartments (blood, cytosol, and mitochondria). In addition to distinguishing between cytosol and mitochondria, the model includes a cytosolic subcompartment for glycolytic metabolic channeling. The model simulations predict the rapid activation of glycogenolysis and lactate production at the onset of ischemia, and support the concept of localization of glycolysis to a cytosolic subcompartment. In addition, simulations show that mitochondrial NADH/NAD(+) is primarily determined by oxygen consumption during ischemia, while cytosolic NADH/NAD(+) and lactate production are largely a function of glycolytic flux during the initial phase, and is controlled by mitochondrial NADH/NAD(+) and the malate-aspartate shuttle during the steady state. Finally, the model predicts that metabolic activation with an abrupt increase in workload requires parallel activation of ATP hydrolysis, glycolysis, mitochondrial dehydrogenases, the electron transport chain, and ADP phosphorylation. Taken together, these studies demonstrate the importance of metabolic compartmentation in the regulation of cardiac energetics in response to acute stress, and they highlight the usefulness of computational models in this line of investigation.

Role of cellular compartmentation in the metabolic response to stress: mechanistic insights from computational models. Publishing Authors By Initials

L Zhou,X Yu,ME Cabrera,WC Stanley,

For similar pathological conditions, signs and symptoms: pathologic processes: stress research abstracts see: pathological conditions, signs and symptoms: pathologic processes: stress research

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Role of cellular compartmentation in the metabolic response to stress: mechanistic insights from computational models. Journal Published:

PUBLICATION TYPE: Review

Journal: Annals of the New York Academy of Sciences

VOLUME: 1080

Page Numbers: 120-39

Journal Abbreviation: Ann. N. Y. Acad. Sci.

ISSN: 0077-8923

DAY: 3

MONTH: Oct

YEAR: 2006

Role of cellular compartmentation in the metabolic response to stress: mechanistic insights from computational models. Information

Number of References: 62

LANGUAGE: eng

NlmUniqueID: 7506858

Role of cellular compartmentation in the metabolic response to stress: mechanistic insights from computational models. Keywords Mesh Terms:

KEYWORDS: Stress

MESH TERMS: metabolism

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Grant and Affiliation Information for Role of cellular compartmentation in the metabolic response to stress: mechanistic insights from computational models.

AFFILIATION: Department of Physiology and Biophysics, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, OH 44106-4970, USA.

Country: United States

AGENCY: United States NHLBI

GRANT: R01 HL 61483

ACRONYM: HL

MEDLINETA: Ann N Y Acad Sci

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