Fatty Acid Oxidation

Fatty Acid Oxidation

• Fatty acid oxidation is a catabolic process for energy production, converting fatty acids into CO2 and water.
• In humans, glucose is the primary source of energy, but when glucose is depleted, fatty acid oxidation occurs.

Fatty Acid Form

• Fatty acids in the body are mainly present in esterified form, such as acylglycerol.
• Lipolysis of acylglycerol releases fatty acids for oxidation, resulting in only free fatty acids (NEFA) being subjected to oxidation.

Fatty Acid Oxidation Steps

Step 1: Activation of Fatty Acid

• Fatty acid activation occurs in the outer mitochondrial membrane.
• Fatty acids are converted into an active intermediate called acyl-CoA, requiring energy from ATP (two ATP) in the presence of coenzyme A and the enzyme acyl-CoA synthetase (thiokinase).

Step 2: Penetration of Inner Mitochondrial Membrane

• Long-chain acyl-CoA (more than 12 carbon atoms) cannot penetrate the inner mitochondrial membrane.
• Carnitine palmitoyltransferase-I (carnitine acyltransferase-I) enzyme converts long-chain acyl-CoA into acylcarnitine, which can penetrate the inner mitochondrial membrane.
• Carnitine-acylcarnitine translocase enzyme acts as an inner membrane exchange transporter, facilitating acylcarnitine penetration.

Step 3: Reformation of Acyl-CoA

• Acylcarnitine reacts with CoA, catalyzed by carnitine palmitoyltransferase-II (carnitine acyltransferase-II) enzyme, reforming acyl-CoA in the mitochondrial matrix and liberating carnitine.

Step 4: β-Oxidation

• In β-oxidation, two carbons at a time are cleaved sequentially from the acyl-CoA molecule, starting from the carboxyl end, with the addition of one molecule of Co-A-SH.
• The chain is broken between α (2) and β (3)-carbon atoms, hence the name β-oxidation.
• The number of acetyl-CoA produced depends on the number of carbon atoms that form acyl-CoA.
• β-oxidation is catalyzed by several enzymes, known collectively as "fatty acid oxidase", producing one mol of FADH2 and NADH + H+ for each cleavage.