Fatty Acid Metabolism Overview

Fatty Acid Metabolism

• Fatty acid metabolism occurs when the body needs energy and blood glucose is low.
• Fatty acids are long acyl CoA chains.
• Dietary fatty acids typically have more than 14 carbons.
• Fatty acids longer than 12 carbons cannot diffuse through the mitochondrial membrane. Therefore, they must be transported.

Carnitine Shuttle

• Acyl CoA is converted to acyl carnitine to cross the mitochondrial membrane. This process is catalyzed by carnitine acyltransferase 1 (CAT1).
• Acyl carnitine is reformed to acyl CoA on the inner mitochondrial membrane side by carnitine acyltransferase 2 (CAT2).
• Carnitine shuttles the acyl CoA across the membrane.

Beta Oxidation

• Once acyl CoA crosses the membrane, it can be oxidized.
• This process involves sequentially removing 2-carbon units through oxidation.
• Each round of beta oxidation produces 1 NADH, 1 FADH2, and 1 acetyl CoA.
• FADH2 and NADH enter the oxidative phosphorylation pathway.
• Acetyl CoA enters the Krebs cycle.

Ketones

• Ketone production often occurs slowly during normal feeding.
• In response to carbohydrate shortages, ketone body production increases.
• This is due to increased beta oxidation and acetyl CoA production exceeding the Krebs cycle's capacity.
• Ketone bodies (such as acetone, acetoacetate) are used instead of carbohydrates to preserve glucose.
• Ketones are primarily used by cardiac and skeletal muscle.
• Diabetic ketoacidosis results from excessive ketone production, typically in untreated diabetes mellitus. Excessive ketone production impairs O2 binding to hemoglobin (hence hyperventilation). Low pH, PCO2, and HCO3-, and high PO2 typically occur.
• Ketones are strong acids.

Citrate Shuttle

• Acetyl CoA cannot directly enter the mitochondria.
• It combines with oxaloacetate to form citrate.
• Citrate crosses the mitochondrial membrane.
• Citrate is then converted back to oxaloacetate and acetyl CoA inside the mitochondria.
• Oxaloacetate is recycled back into the Krebs cycle.
• Acetyl CoA is used for energy production or fatty acid synthesis.