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Functional coupling between glycolysis and sarcoplasmic reticulum Ca2+ transport
K Y Xu1, J L Zweier, L C Becker
1Department of Medicine, Johns Hopkins Medical Institutions, Baltimore, Md, USA.
Circulation Research
|July 1, 1995
Summary
Glycolytic enzymes attached to sarcoplasmic reticulum (SR) membranes generate ATP, fueling calcium transport. This localized energy production is crucial for cellular calcium homeostasis.
Area of Science:
- Biochemistry
- Cellular Physiology
- Muscle Biology
Background:
- Sarcoplasmic reticulum (SR) calcium (Ca2+) transport is vital for muscle contraction and relaxation.
- The energy source for SR Ca2+ pumps, primarily ATP, is typically assumed to be cytosolic.
- Investigating localized ATP production for SR functions is essential for understanding cellular energy dynamics.
Purpose of the Study:
- To determine if glycolytic enzymes associate with SR membranes.
- To assess if SR-associated glycolysis can functionally support Ca2+ transport.
- To explore the role of endogenously produced ATP in SR Ca2+ homeostasis.
Main Methods:
- Isolation of right-side-out SR vesicles from rabbit skeletal and cardiac muscle.
- Measurement of 45Ca transport in response to glycolytic substrates or exogenous ATP.
- Assessment of ATP production dependency using enzyme inhibitors and ATP traps.
Main Results:
- The complete glycolytic enzyme chain, from aldolase to pyruvate kinase, was found associated with SR vesicles.
- Inhibition of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) abolished Ca2+ transport, which was restored by pyruvate kinase (PK) substrates.
- Endogenously produced ATP supported significantly more Ca2+ transport than exogenous ATP, especially at low concentrations.
Conclusions:
- Glycolytic enzymes are functionally coupled to SR Ca2+ transport.
- ATP generated by SR-associated glycolytic enzymes can directly fuel the SR Ca2+ pump.
- This localized energy production likely plays a key role in maintaining cellular Ca2+ homeostasis.