Beta-oxidation is the primary pathway for breaking down fatty acids to generate energy.
In this process, fatty acids are converted into acetyl-CoA, which enters the citric acid cycle (TCA cycle) to produce ATP.
Here’s a detailed explanation of the beta-oxidation of palmitic acid, a saturated fatty acid with 16 carbons (C16:0).
1) Activation and Transport into Mitochondria
Activation
Process: Before beta-oxidation can occur, palmitic acid must be activated by attaching a coenzyme A (CoA) molecule.
Enzyme: Acyl-CoA synthetase (also called fatty acid thiokinase).
Product: Palmitoyl-CoA.
Energy: This reaction occurs in the cytosol and consumes one ATP molecule.
Transport
Palmitoyl-CoA needs to be transported into the mitochondrial matrix for β-oxidation.
1) Step 1
Carnitine palmitoyltransferase I (CPT I), located on the outer mitochondrial membrane, transfers the fatty acyl group from CoA to carnitine, forming acyl-carnitine.
2) Step 2
Acyl-carnitine is transported across the inner mitochondrial membrane by the carnitine-acylcarnitine translocase enzyme.
3) Step 3
Inside the mitochondrial matrix, carnitine palmitoyltransferase II (CPT II) transfers the fatty acyl group from carnitine back to CoA, regenerating acyl-CoA and releasing free carnitine.
2) Beta-Oxidation Steps
Beta-oxidation consists of a series of four enzymatic reactions that are repeated until the entire fatty acid chain is broken down into acetyl-CoA units.
β-Oxidation of saturated fatty acid (Palmitic acid)
A) Dehydrogenation
Enzyme: Acyl-CoA dehydrogenase.
Process: The first step introduces a double bond between the α (alpha) and β (beta) carbons of the fatty acid chain.
Products: Formation of trans-enoyl-CoA and reduction of flavin adenine dinucleotide (FAD) to FADH2.
B) Hydration
Enzyme: Enoyl-CoA hydratase.
Process: A water molecule is added across the double bond formed in the previous step.
Product: L-3-hydroxyacyl-CoA.
C) Dehydrogenation
Enzyme: 3-hydroxyacyl-CoA dehydrogenase.
Process: The hydroxyl group on the β-carbon is oxidized to a carbonyl group (ketone), forming β-ketoacyl-CoA.
Product: Reduction of NAD+ to NADH.
D) Thiolysis
Enzyme: β-ketothiolase.
Process: The bond between the α and β carbons is cleaved.
Products: One molecule of acetyl-CoA and a fatty acyl-CoA that is two carbons shorter.
Repetition
For palmitic acid (C16:0), these four reactions are repeated seven times, producing a total of eight acetyl-CoA molecules.
3) Energy Production
TCA Cycle Entry: The acetyl-CoA molecules generated through beta-oxidation enter the TCA cycle.
Additional Products: The TCA cycle generates more NADH, FADH2, and ATP.
Electron Transport Chain: NADH and FADH2 produced during beta-oxidation and the TCA cycle are used in the electron transport chain to generate ATP via oxidative phosphorylation.