Fatty Acid Oxidation Quiz

Fatty Acid Oxidation

• Fatty acid oxidation releases the maximum energy among food sources.
• One gram of fat produces approximately 9 Kcal of energy.
• Fatty acids are derived from the diet and lipolysis of adipose tissue.
• Types of fatty acid oxidation include beta (β) oxidation (most common), alpha (α) oxidation, and omega (ω) oxidation.

Beta-Oxidation

• Occurs in the mitochondria.
• Specific organ sites include liver, kidney, and heart.
• Involves three steps:
  • Activation of fatty acids to acyl CoA: fatty acids are activated in the cytoplasm before entering the mitochondria by acyl-CoA synthetase or thiokinase. This process requires ATP.
  • Transport of Acyl CoA into Mitochondria via the Carnitine Shuttle: The inner mitochondrial membrane is impermeable to acyl CoA. The carnitine shuttle facilitates transport using:
    • Carnitine acyltransferase I (in outer mitochondrial membrane)
    • Carnitine acylcarnitine translocase (in inner mitochondrial membrane)
    • Carnitine acyltransferase II (in inner mitochondrial membrane).
  • Oxidation in the Mitochondrial Matrix: A series of enzymatic reactions within the mitochondrial matrix break down acyl-CoA into acetyl-CoA, FADH₂, and NADH.

Oxidation in the Mitochondrial Matrix

• Occurs in the mitochondrial matrix.
• A series of enzymatic reactions break down acyl-CoA into acetyl-CoA, FADH₂, and NADH.
• The reactions proceed sequentially producing, FADH2, NADH, and acetyl CoA which enters the citric acid cycle.

Regulation of FA Oxidation

• Glucose oxidation is inversely related to fatty acid oxidation. In diabetes mellitus or starvation, where glucose is insufficient, fatty acid oxidation increases.
• Starvation and low blood glucose levels increase lipolysis, releasing fatty acids, and stimulating fatty acid oxidation.
• Insulin and carbohydrate intake inhibit fatty acid oxidation.

Energy Production from Beta-Oxidation

• Palmitic acid (16-carbon fatty acid) undergoes beta-oxidation 7 times.
• Each cycle produces one FADH₂ and one NADH + H⁺.
• Acetyl-CoA enters the citric acid cycle producing ATP.
• 7 cycles produce 7FADH₂ and 7NADH+H⁺ and 8 acetyl CoA.
• 7 cycles * 5ATP (from FADH₂) + 7 cycles * 3ATP = 35 ATP
• 8 acetyl CoA * 12 ATP (from citric acid cycle) = 96 ATP
• Activation of palmitic acid to acyl-CoA uses 2 ATP
• Total energy yield from beta-oxidation of palmitic acid = 129 ATP

Odd Number Fatty Acid Oxidation

• Fatty acids with an odd number of carbons are oxidized similarly to even-numbered fatty acids until a 3-carbon residue (propionyl CoA) remains.
• Propionyl CoA is converted to succinyl CoA, entering the citric acid cycle for further energy production or glucose synthesis (gluconeogenesis).

Alpha (α) Oxidation

• A minor pathway.
• Occurs primarily in the brain and liver.
• Removes one carbon atom at a time, from a specific position.
• Does not require coenzyme A (CoA).
• Important for the metabolism of methylated fatty acids like phytanic acid (found in ruminant tissues and dairy products).
• The methyl group in phytanic acid blocks beta-oxidation, hence, it undergoes alpha-oxidation.

Metabolism of Ketone Bodies

• During high rates of fatty acid oxidation (particularly in the liver), the production of acetyl-CoA exceeds the capacity of the citric acid cycle.
• This excess acetyl-CoA is converted into ketone bodies (acetoacetic acid, beta-hydroxybutyric acid, and acetone).
• Ketone bodies are transported to other tissues (especially the brain) as alternative energy sources during prolonged fasting or starvation.

Importance of Ketone Bodies

• Critical energy source for tissues, particularly the brain.
• Utilizable in prolonged fasting or starvation when glucose is scarce.
• The brain can utilize ketone bodies after a few days (5 to 10) of starvation.
• The total blood concentration of ketone bodies does not exceed 2 mg/dl.

Ketone Body Synthesis (Ketogenesis)

• The synthesis process is called ketogenesis which occurs in the liver.
• Ketone bodies are made from acetyl CoA.
• Acetoacetyl CoA is a key intermediate formed by two pathways (condensation of two acetyl CoA molecules or during beta-oxidation.)
• Acetoacetate is generated by decarboxylation from acetoacetyl CoA.
• Acetoacetate can also be reduced to beta-hydroxybutyrate or decarboxylated to generate acetone

Regulation of Ketogenesis

• Lipolysis in adipose tissue is a primary driver of ketogenesis through increasing free fatty acid (FFA) delivery to the liver.
• Increased liver carnitine palmitoyltransferase-I (CPT-I) activity and serum free fatty acid levels.
• In the fed state, high insulin /glucagon levels inhibit CPT-I activity, thus reducing ketogenesis, where malonyl-CoA inhibits CPT-I.