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Myocardial citrate metabolism in control subjects and patients with coronary artery disease
Insights
In patients with coronary artery disease (CAD), myocardial citrate release is linked to free fatty acid (FFA) levels, suggesting FFA suppresses heart glucose utilization via citrate inhibition.
Area of Science:
- Cardiology
- Biochemistry
- Metabolic Research
Background:
- Myocardial metabolism is crucial for heart function.
- Free fatty acids (FFAs) are a primary energy source for the heart.
- Citrate plays a role in regulating glucose metabolism.
Purpose of the Study:
- To investigate myocardial citrate release in patients with coronary artery disease (CAD) and controls.
- To explore the relationship between citrate, FFAs, and glucose metabolism in the heart.
- To determine if FFAs suppress myocardial glucose utilization through citrate inhibition.
Main Methods:
- Measured arterio-coronary sinus (A-Cs) plasma citrate and glucose differences in fasting subjects.
- Correlated citrate and glucose differences with arterial plasma FFA concentrations.
- Assessed myocardial oxygen consumption capacity using heart rate and blood pressure during exercise tolerance tests.
Main Results:
- Significant myocardial citrate release was observed in both CAD patients and controls.
- Negative A-Cs plasma citrate differences correlated positively with arterial FFA concentrations and negatively with A-Cs glucose differences.
- The capacity of plasma FFAs to increase myocardial citrate release was higher in controls than in CAD patients.
- This capacity was positively related to myocardial oxygen consumption capacity.
Conclusions:
- Citrate inhibition of phosphofructokinase is important for regulating myocardial glucose metabolism.
- Free fatty acids suppress myocardial glucose utilization via citrate inhibition.
- Impaired FFA regulation of citrate release may contribute to altered cardiac metabolism in CAD.
Abstract:
A significant release of citrate across the myocardium was demonstrated in twenty-two patients with coronary artery disease (CAD) and in ten control subjects in fasting resting state. In both groups, increasingly negative arterio-coronary sinus (A-Cs) plasma citrate differences correlated positively to arterial plasma free fatty acid (FFA)concentrations and negatively to (A-Cs) differences of plasma glucose. This supports the hypothesis that a citrate inhibition of glycolysis at the site of phosphofructokinase is of regulatory importance for myocardial glucose metabolism, and suggests that FFA supress glucose utilization by the heart in many by this mechanism. The capacity of plasma FFA to increase myocardial citrate release was significantly higher in controls than in patients with CAD, and was found to be positively related to myocardial capacity of oxygen consumption as estimated from the product of heart rate and systolic blood pressure during an exercise tolerance test.