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AAT Bioquest

What are the stages of fatty acid oxidation?

Posted July 28, 2022


Answer

Fatty acid oxidation takes place in four stages - dehydrogenation, hydration, oxidation, and thiolysis. These four stages keep repeating until the whole molecule is oxidized. Each of these four stages is catalyzed by a different enzyme.

Stage 1: Dehydrogenation

In this first stage, the enzyme acyl CoA dehydrogenase oxidizes acyl-CoA by removing the hydrogen atoms between the second and third carbons (C2 and C3) of the acyl-CoA chain. This forms a double bond between carbons C2 and C3. The end product of this reaction is trans-delta 2-enoyl CoA.

Stage 2: Hydration 

The second stage requires water to carry out the hydration. In this stage, the enzyme enoyl-CoA hydratase adds water across the double bond between C2 and C3. This replaces the double bond with a hydroxyl group (OH) in C2, resulting in the formation of L-β-hydroxyacyl CoA.

Stage 3: Oxidation

In the third stage, NAD+ oxidizes the hydroxyl group in C2 of L-β-hydroxyacyl CoA. This reaction is catalyzed by the enzyme 3-hydroxyacyl-CoA dehydrogenase, which generates NADH. β-ketoacyl CoA and NADH + H are the two end products of oxidation. 

Stage 4: Thiolysis

In the fourth stage, a thiol group (SH) of another CoA molecule (CoA-SH) cleaves the β-ketoacyl CoA between C2 and C3. The reaction is catalyzed by the enzyme β-ketothiolase. The end products are a new acyl-CoA chain that is two carbons shorter than the original acyl-CoA at the start of the beta oxidation cycle and an acetyl-CoA molecule with the original two first carbons (C1 and C2). 

The shortened acyl-CoA reenters the beta-oxidation pathway while the acetyl-CoA molecule enters citric acid or Krebs cycle to product adenosine triphosphate (ATP), which is used as energy. 

Additional resources

Mitochondrial β-oxidation of saturated fatty acids in humans

Screen Quest™ Fluorimetric Fatty Acid Uptake Assay Kit

Dehydrogenases