Beta oxidation

In biochemistry and metabolism, beta oxidation (also β-oxidation) is the catabolic process by which fatty acid molecules are broken down in the cytosol in prokaryotes and in the mitochondria in eukaryotes to generate acetyl-CoA.

It is named as such because the beta carbon of the fatty acid chain undergoes oxidation and is converted to a carbonyl group to start the cycle all over again.

The overall reaction for one cycle of beta oxidation is: Free fatty acids cannot penetrate any biological membrane due to their negative charge.

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

Both the fatty acid beta-oxidation and the TCA cycle produce NADH and FADH2, which are used by the electron transport chain to generate ATP.

When this infusion of citric acid cycle intermediates exceeds cataplerotic demand (such as for aspartate or glutamate synthesis), some of them can be extracted to the gluconeogenesis pathway, in the liver and kidneys, through phosphoenolpyruvate carboxykinase, and converted to free glucose.

The enzyme catalase, found primarily in peroxisomes and the cytosol of erythrocytes (and sometimes in mitochondria[12]), converts the hydrogen peroxide into water and oxygen.

This breakdown is as follows: For an even-numbered saturated fat (Cn), 0.5 * n - 1 oxidations are necessary, and the final process yields an additional acetyl CoA.

Furthermore, studies indicate that lipid disorders are involved in diverse aspects of tumorigenesis, and fatty acid metabolism makes malignant cells more resistant to a hypoxic environment.

Medium-chain acyl-coenzyme A dehydrogenase (MCAD) deficiency[18] is the most common fatty acid β-oxidation disorder and a prevalent metabolic congenital error It is often identified through newborn screening.

Medium-chain acyl-CoA dehydrogenase (MCAD) plays a crucial role in mitochondrial fatty acid β-oxidation, a process vital for generating energy during extended fasting or high-energy demand periods.

This reaction is essential for the subsequent steps in beta oxidation that lead to the production of acetyl-CoA, NADH, and FADH2, which are important for generating ATP, the energy currency of the cell.

Long-chain hydroxyacyl-CoA dehydrogenase (LCHAD) deficiency is a condition that affects mitochondrial function due to enzyme impairments.

In the β-oxidation cycle, VLCAD's role involves the removal of two hydrogen atoms from the acyl-CoA molecule, forming a double bond and converting it into trans-2-enoyl-CoA.

A diagrammatic illustration of the process of lipolysis (in a fat cell) induced by high epinephrine and low insulin levels in the blood. Epinephrine binds to a beta-adrenergic receptor in the cell wall of the adipocyte, which causes cAMP to be generated inside the cell. The cAMP activates a protein kinase , which phosphorylates and activates a hormone-sensitive lipase in the fat cell. This lipase cleaves free fatty acids from their attachment to glycerol in the adipocyte. The free fatty acids and glycerol are then released into the blood.
A diagrammatic illustration of the transport of free fatty acids in the blood attached to plasma albumin , its diffusion across the cell membrane using a protein transporter, and its activation, using ATP , to form acyl-CoA in the cytosol . The illustration is of a 12 carbon fatty acid.
A diagrammatic illustration of the transfer of an acyl-CoA molecule across the inner membrane of the mitochondrion by carnitine-acyl-CoA transferase (CAT). The illustrated acyl chain is 12 carbon atoms long. CAT is inhibited by high concentrations of malonyl-CoA (the first committed step in fatty acid synthesis ) in the cytoplasm. This means that fatty acid synthesis and fatty acid catabolism cannot occur simultaneously in any given cell.
A diagrammatic illustration of the process of the beta-oxidation of an acyl-CoA molecule in the mitochondrial matrix. During this process an acyl-CoA molecule which is 2 carbons shorter than it was at the beginning of the process is formed. Acetyl-CoA, water and 5 ATP molecules are the other products of each beta-oxidative event, until the entire acyl-CoA molecule has been reduced to a set of acetyl-CoA molecules.
General Mechanism of Beta Oxidation
Propionyl-CoA modification after beta oxidation of odd-chain fatty acid
Complete beta oxidation of linoleic acid (an unsaturated fatty acid).
Steps in beta-oxidation of odd-numbered saturated fatty acids [ 15 ]
Schematic demonstrating mitochondrial fatty acid beta-oxidation and effects of long-chain 3-hydroxyacyl-coenzyme A dehydrogenase deficiency, LCHAD deficiency