Beta oxidation

In biochemistry and metabolism, beta-oxidation is the catabolic process by which fatty acid molecules are broken down. See also [1].

Activation and membrane transport

1) Long-chain-fatty-acid—CoA ligase catalyzes the reaction between a fatty acid with ATP to give a fatty acyl adenylate, plus inorganic pyrophosphate, which then reacts with free coenzyme A to give a fatty acyl-CoA ester and AMP.

2) If the fatty acyl-CoA has a long chain, then the shuttle must be utilized:

a) Acyl-CoA is transferred to the hydroxyl group of carnitine by carnitine palmitoyltransferase I (see Carnitine palmitoyltransferase), located on the cytosolic faces of the outer and inner mitochondrial membranes.

b) Acyl-carnitine is shuttled inside by a carnitine-acylcarnitine translocase, as a carnitine is shuttled outside.

c) Acyl-carnitine is converted back to acyl-CoA by carnitine palmitoyltransferase II (see Carnitine palmitoyltransferase), located on the interior face of the inner mitochondrial membrane. The liberated carnitine is shuttled back to the cytosol, as an acyl-carnitine is shuttled into the matrix.

3) If the fatty acyl-CoA contains a short chain, these short-chain fatty acids can simply diffuse through the inner mitochondrial membrane.

General mechanism

Once the fatty acid is inside the mitochondrial matrix, beta-oxidation occurs by cleaving two carbons every cycle to form acetyl-CoA. The process consists of 4 steps.

1) A long-chain fatty acid is dehydrogenated to create a trans double bond between C2 and C3. This is catalyzed by acyl-CoA dehydrogenase to produce trans-delta 2-enoyl CoA. It uses FAD as an electron acceptor and it is reduced to FADH2.

• Acyl-CoA dehydrogenase
• Glutaryl-CoA dehydrogenase

2) Trans-delta2-enoyl CoA is hydrated at the double bond to produce L-3-hydroxyacyl CoA by enoyl-CoA hydratase.

3) L-3-hydroxyacyl CoA is dehydrogenated again to create 3-ketoacyl CoA by 3-hydroxyacyl CoA dehydrogenase. This enzyme uses NAD as an electron acceptor.

4) Thiolysis occurs between C2 and C3 (alpha and beta carbons) of 3-ketoacyl CoA. Thiolase enzyme catalyzes the reaction when a new molecule of coenzyme A breaks the bond by nucleophilic attack on C3. This releases the first two carbon units, as acetyl CoA, and a fatty acyl CoA minus two carbons. The process continues until all of the carbons in the fatty acid are turned into acetyl CoA.

Odd-numbered saturated fatty acids

Chains with an odd-number of carbons are oxidized in the same manner as even-numbered chains, but the final products are propionyl-CoA and Acetyl CoA

Propionyl-CoA is first carboxylated using a bicarbonate ion into D-stereoisomer of methylmalonyl-CoA, in a reaction that involves a biotin co-factor, ATP, and the enzyme propionyl-CoA carboxylase. The bicarbonate ion's carbon is added to the middle carbon of propionyl-CoA, forming a D-methylmalonyl-CoA. However, the D conformation is enzymatically converted into the L conformation by methylmalonyl-CoA epimerase, then it undergoes intramolecular rearrangement, which is catalyzed by methylmalonyl-CoA mutase (requiring B12 as a coenzyme) to form succinyl-CoA. The succinyl-CoA formed can then enter the citric acid cycle.