Fuels of the human heart

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Fuels of the human heart

• Presented by Ri ???

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Introduction

• 35 kg ATP was synthesized to keep pumping(1994,
  Taegtmeyer)
• O2
• Fuels
• Continuous coronary circulation
• Cardiac glycogen as a reserve

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Uptake of Fuels

• Energy demand
• Arterial concentration

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Intermediary metabolism

• Fig 11-1

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Fasted state
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Fasted state

• When fatty acids are oxidized
• Glucose oxidation is inhibited
• Glucose is converted to glycogen

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Fed state
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Other Fuels?

• Lactate
• During acute exercise
• Inhibit glucose oxidation and FFA uptake
• Ketone bodies
• Starvation
• Severe diabetic ketosis

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Glucose uptake

• Via GLUT 4 and GLUT 1
• No energy required for transport
• Stimulated by
• Increased heart work
• In the fed state
• Hypoxia or ischemia

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Glucose uptake

• Inhibited by
• Low workload
• Fasted state
• Severe diabetes mellitus
• Insulin send GLUT from cytosol to cell membrane

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Fate of glucose
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Fate of glucose

• Pyruvate DeHydrogenase(PDH)
• Stimulate by
• Increased heart work
• Catecholamines
• High glycolytic rates of the fed state
• Inhibited by
• NADH2 formed by ischemia or hypoxia
• Fatty acid oxidation

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Function of Cardiac Glycogen

• Potential source of myocardial energy
• 3 ATP through glycolysis
• Standard amount of ATP through citrate cycle
• Energy source during myocardial hypoxia or
  ischemia

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Uptake of FFA
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Beta-oxidation

• Converts intramitochondrial long-chain acyl CoA
  to acetyl CoA
• Remove acetyl CoA from the carboxyl end(-COOH) of
  the chain

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Increased heart work

• Increased ATP -gt ADP
• NAD/NADH2 ratio increase
• Stimulate key enzymes of the citrate cycle

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Anaerobic glycolysis

• Any state of suboptimal oxygenation that
  accelerates glycolysis and increases the
  production of lactate
• Produce 1/20 ATP of aerobic glycolysis

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Glycolysis in Ischemia
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Glycolysis in Ischemia

• Phosphofructokinase(PFK)
• Sensitive to energy status
• Increased activity while ADP increased
• Glyceraldehyde 3-phosphate dehydrogenase(GAPDH)
• Inhibited by lactate, protons, and NADH2

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Ischemia

• Mild ischemia or hypoxia
• Stimulate glycolysis
• Provide oxygen-independent ATP
• Severe ischemia
• Inhibited glycolysis by
• Low rate of delivery of glucose
• Glycogen depletion
• Intracellular acidosis

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Ischemia
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Metabolic Therapies of Ischemia

• Lessen myocardial oxygen demand
• Drug such as beta-blocker
• Reperfusion of blood flow
• NTG, thrombolysis, PTCA

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Conclusion

• Myocardial fuels
• Omnivorous
• FFA usually the major myocardial fuel
• Glucose only after a high-carbohydrate meal or
  ischemia
• Aerobic -gt acetyl CoA
• Anaerobic -gt lactate

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Thank you for your attention !!