What question did this study set out to answer?

Determine whether glycolytic enzymes associate with sarcoplasmic reticulum membranes and whether local glycolytic metabolism directly supports Ca2+ active transport.

July 1, 1995Circulation Research

Functional Coupling Between Glycolysis and Sarcoplasmic Reticulum Ca ²⁺ Transport

Q: What is the clinical evidence from this study?

Population: Basic science (rabbit skeletal and cardiac muscle). Intervention: Glycolytic substrates and cofactors (endogenous ATP production) vs. Exogenous ATP. Primary outcome: Intravesicular 45Ca transport.

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Key result

Endogenously produced ATP via SR-associated glycolytic enzymes supported 15-fold more 45Ca transport than exogenously supplied ATP at low concentrations, indicating functional coupling.

Key Points

Determine whether glycolytic enzymes associate with sarcoplasmic reticulum membranes and whether local glycolytic metabolism directly supports Ca2+ active transport.
Isolated sealed right-side-out sarcoplasmic reticulum vesicles from rabbit cardiac and skeletal muscle using step sucrose gradient centrifugation.
Assayed thapsigargin-sensitive 45Ca transport after adding pathway-specific glycolytic substrates and cofactors or exogenous ATP.
Tested substrate channeling by measuring 45Ca transport in the presence of a soluble hexokinase ATP trap and at low nucleotide concentrations (10 to 50 nmol/L).
The entire glycolytic enzyme sequence from aldolase to pyruvate kinase remained bound to sarcoplasmic reticulum vesicles in cardiac and skeletal muscle.
Addition of a hexokinase ATP trap eliminated 45Ca transport powered by exogenous ATP but had minimal effect on transport driven by endogenously generated glycolytic ATP.
Endogenous ATP produced from ADP and phosphoenolpyruvate generated 15-fold greater 45Ca transport than identical concentrations of exogenous ATP (10 to 50 nmol/L).

Structured PICO

Population

Sealed right-side-out sarcoplasmic reticulum (SR) vesicles isolated from rabbit skeletal and cardiac muscle

Intervention

Glycolytic substrates and cofactors (e.g., fructose-1,6-diphosphate, phosphoenolpyruvate) to generate endogenous ATP

Comparator

Exogenous ATP or addition of inhibitors (iodoacetic acid, hexokinase ATP trap)

Outcome

Intravesicular 45Ca transport sensitive to thapsigarginsurrogate

Glycolytic enzymes are physically associated with the sarcoplasmic reticulum and functionally couple ATP production directly to the Ca2+ pump, highlighting a localized energy supply mechanism for cellular Ca2+ homeostasis.

Discussion

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Implication

Localized SR-glycolytic ATP coupling may aid Ca2+ handling in stressed myocardium; hypothesis-generating for metabolic targets in HF, needs in vivo confirmation.

Cite This Study

Xu et al. (1995) studied Basic science (rabbit skeletal and cardiac muscle). Glycolytic substrates and cofactors (endogenous ATP production) vs. Exogenous ATP was evaluated on Intravesicular 45Ca transport. Endogenously produced ATP via SR-associated glycolytic enzymes supported 15-fold more 45Ca transport than exogenously supplied ATP at low concentrations, indicating functional coupling.

synapsesocial.com/papers/6a0aafea48609dcc0aac95d5 https://doi.org/10.1161/01.res.77.1.88

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Implication

Localized SR-glycolytic ATP coupling may aid Ca2+ handling in stressed myocardium; hypothesis-generating for metabolic targets in HF, needs in vivo confirmation.

Functional Coupling Between Glycolysis and Sarcoplasmic Reticulum Ca ²⁺ Transport

Key Points

Structured PICO

Discussion

Implication

Cite This Study

Functional Coupling Between Glycolysis and Sarcoplasmic Reticulum Ca ²⁺ Transport

Key Points

Structured PICO

Discussion

Implication

Cite This Study

Also Consider

Also Consider