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Malate-aspartate shuttle, cytoplasmic NADH redox potential, and energetics in vascular smooth muscle

J T Barron1, L Gu, J E Parrillo

  • 1Department of Medicine, Rush Medical College, Chicago, IL, 60612, USA.

Journal of Molecular and Cellular Cardiology
|September 17, 1998
PubMed

Insights

Inhibition of the malate-aspartate shuttle impairs vascular smooth muscle energetics by increasing cytoplasmic NADH. Octanoate addition normalized these effects, highlighting the shuttle's role in NADH clearance.

Area of Science:

  • Biochemistry
  • Cellular Physiology
  • Vascular Biology

Background:

  • The malate-aspartate shuttle facilitates NADH transport into mitochondria.
  • Cytoplasmic NADH/NAD ratio impacts cellular energy metabolism.
  • Vascular smooth muscle energetics are crucial for blood pressure regulation.

Purpose of the Study:

  • To investigate the role of the malate-aspartate shuttle in vascular smooth muscle energetics.
  • To determine the impact of shuttle inhibition on cytoplasmic redox state and mitochondrial function.
  • To explore potential interventions for shuttle inhibition-induced metabolic dysfunction.

Main Methods:

  • Porcine carotid arteries were incubated with amino-oxyacetic acid, a malate-aspartate shuttle inhibitor.
  • Oxygen consumption, phosphocreatine content, and tricarboxylic acid cycle activity were measured.
  • Glycolysis, lactate production, glucose oxidation, and metabolite redox couples (lactate/pyruvate, glycerol-3-phosphate/dihydroxyacetone phosphate) were analyzed.
  • The effect of octanoate, a fatty acid, was assessed.

Main Results:

  • Amino-oxyacetic acid inhibited O2 consumption by 21% and decreased phosphocreatine.
  • Shuttle inhibition increased glycolysis and lactate production while inhibiting glucose oxidation.
  • Elevated cytoplasmic NADH/NAD ratio was indicated by increased lactate/pyruvate and glycerol-3-phosphate/dihydroxyacetone phosphate ratios.
  • Octanoate addition normalized the adverse energetic effects.

Conclusions:

  • The malate-aspartate shuttle is essential for clearing cytoplasmic NADH reducing equivalents in vascular smooth muscle.
  • Shuttle activity influences glucose oxidation and lactate production.
  • Increased cytoplasmic NADH redox potential impairs mitochondrial energy metabolism, supporting the study's hypothesis.

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