Fatty Acid Oxidation Quiz

Fatty Acid Oxidation

• Oxidation of fatty acids provides the most energy compared to other food, with 1 gram of fat producing approximately 9 Kcal.
• Fatty acids derive from diet or mobilization from adipose tissue through lipolysis.
• Types of fatty acid oxidation include beta (β) oxidation (most common), alpha (α) oxidation, and omega (ω) oxidation.

Beta-Oxidation

• Site: Occurs intracellularly within mitochondria in organs like liver, kidney, and heart.
• Steps:
  • Activation: Fatty acids are activated in the cytoplasm by acyl-CoA synthetase (or thiokinase), requiring ATP, to form acyl-CoA.
  • Transport: Acyl-CoA is transported into the mitochondria via a carnitine shuttle. This involves three enzymes: carnitine acyltransferase I (in outer membrane), carnitine acylcarnitine translocase (inner membrane), and carnitine acyltransferase II (inner membrane).
  • Oxidation: Oxidation occurs in the mitochondrial matrix involving a series of reactions: dehydrogenases, hydratases, and thiolases. These steps produce acetyl-CoA, FADH₂, and NADH.

Energy Production from β-oxidation of Palmitic Acid

• Palmitic acid (a saturated fatty acid) undergoes β-oxidation 7 times.
• Each cycle generates one FADH₂ and one NADH + H⁺.
• Acetyl-CoA produced enters the Krebs cycle, generating 12 ATP per molecule.
• 7 cycles of β-oxidation yield 7 FADH₂ and 7 NADH+H.
• 8 molecules of Acetyl-CoA are produced, generating 96 ATP.
  • Activation of palmitic acid requires 2 ATP.

Regulation of FA Oxidation

• β-oxidation increases during decreased glucose oxidation (e.g., in diabetes mellitus and starvation).
• This is linked to increased lipolysis, releasing fatty acids into the blood.
• β-oxidation is inhibited by insulin and carbohydrate-rich meals. In these states, glucose oxidation is favoured, and fatty acid release is decreased.

Oxidation of Odd Number Fatty Acids

• Odd-numbered fatty acids are oxidized through beta-oxidation.
• The final 3-carbon molecule (propionyl-CoA) is converted to succinyl-CoA.
• Succinyl-CoA enters the citric acid cycle and can be used for gluconeogenesis.

Alpha (α) Oxidation

• Occurs primarily in the brain and liver, but is a minor pathway.
• Removes one carbon at a time from the carbon position.
• It does not utilize CoA and doesn't generate significant energy.
• Important for the metabolism of dietary methylated fatty acids, for example phytanic acid (found in ruminants and dairy products).

Metabolism of Ketone Bodies

• During high rates of fatty acid oxidation (especially in the liver), acetyl-CoA production exceeds the capacity of the citric acid cycle. This leads to the synthesis of ketone bodies.
• Ketone bodies (acetoacetic acid, β-hydroxybutyric acid, and acetone) are exported to extrahepatic tissues as a fuel source.
• Important fuel during prolonged fasting and starvation especially for the brain.

Ketone Body Synthesis (Ketogenesis)

• Definition: Ketogenesis is the synthesis of ketone bodies from acetyl CoA.
• Site: Occurs in the mitochondria of liver cells.
• Steps:
  • Acetoacetyl-CoA forms from two acetyl-CoA molecules (directly or through beta-oxidation).
  • Acetoacetate is produced from acetoacetyl-CoA.
  • Acetoacetate can be converted to acetone or β-hydroxybutyrate.

Regulation of Ketogenesis

• Ketogenesis is increased by lipolysis (breakdown of fats) in adipose tissue, rising free fatty acid (FFA) levels, and increased FFA uptake by the liver.
• Increased activity of carnitine palmitoyl transferase-1 in the liver facilitates the transport of fatty acids into the mitochondria for oxidation, thus enhancing ketogenesis.
• Malonyl-CoA, an inhibitor of fatty acid transport, suppresses ketogenesis in the fed state (sufficient glucose intake).
• Starvation conditions lead to reduced inhibition and elevated ketogenesis.