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Renin Angiotensin Mechanism.

Beta Oxidation of Fatty Acids.

 

Definition:

  • Beta-oxidation is the catabolic process by which fatty acid molecules are broken down in the mitochondria to generate acetyl-CoA.

  • Acetyl-CoA enters the citric acid cycle while NADH and FADH2, which are coenzymes, are used in the electron transport chain.

  • It is called “beta oxidation” because the beta carbon of the fatty acid undergoes oxidation to a carbonyl group.

Location:

  • Mitochondria.

Pathway:

  • In the mitochondria, the fatty acid undergoes a series of oxidation and hydration reactions, which results in the removal of a two-carbon group (in the form of acetyl CoA) from the fatty acid chain as well as the formation of one NADH and one FADH2, which enter the electron transport chain to form five ATP.

  • The acetyl CoA formed will enter the citric acid cycle and then the electron transport chain, leading to the formation of another 12 ATP. 

  • The cycle continues, with each turn of the cycle removing another two-carbon group, until the formerly long-chain fatty acid has been reduced to acetyl CoA.

Steps:

  1. Activation of fatty acids.

  2. Transport of fatty acyl-CoA from the cytosol into mitochondria.

  3. β-Oxidation of fatty acids.

Important Enzymes involved:

  1. Acyl CoA dehydrogenase: 

    1. Forms a double bond between the α and β carbon atoms in the fatty acid chain. Produces one FADH2.

  2. Enoyl CoA hydratase: 

    1. Incorporates a water molecule into the fatty acid chain, thereby breaking the double bond between the α and β carbon atoms.

  3. 3-Hydroxy-acyl CoA dehydrogenase: 

    1. Dehydrogenates the fatty acid chain again, thereby forming a double bond between the β carbon and the oxygen molecule. Produces one NADPH.

  4. Acyl CoA acyltransferase: 

    1. Cleaves acetyl CoA off the end of the fatty acid chain with the addition of CoA to the β carbon.

  1. Activation of fatty acids:

  • In the cytoplasm, long-chain fatty acids are activated by ATP and coenzyme A, and fatty acyl-CoA is formed. 

  • Short-chain fatty acids are activated in mitochondria.

  • The ATP is converted to AMP and pyrophosphate (PPi), which is cleaved by pyrophosphatase to two inorganic phosphates (2 Pi). 

  1. Transport of fatty acyl-CoA from the cytosol into mitochondria:

  • Fatty acyl-CoA from the cytoplasm reacts with carnitine in the outer mitochondrial membrane, forming fatty acylcarnitine. 

  • The enzyme is carnitine acyltransferase I (CAT I).

  • Carnitine acyltransferase I, which catalyzes the transfer of acyl groups from coenzyme A to carnitine, is inhibited by malonyl-CoA, an intermediate in fatty acid synthesis. Therefore, when fatty acids are being synthesized in the cytoplasm, malonyl-CoA inhibits their transport into mitochondria and, thus, prevents a futile cycle (synthesis followed by immediate degradation).

  • Inside the mitochondrion, the fatty acyl-CoA undergoes beta-oxidation.

  1. β-Oxidation of fatty acids:

  • FAD accepts hydrogens from a fatty acyl-CoA in the first step. A double bond is produced between the α- and β-carbons, and an enoyl-CoA is formed. The FADH2 that is produced interacts with the electron transport chain, generating ATP.

    • Enzyme: Acyl-CoA dehydrogenase.

  • H2O adds across the double bond, and a β-hydroxyacyl-CoA is formed.

    • Enzyme: Enoyl-CoA hydratase

  • β -Hydroxyacyl-CoA is oxidized by NAD+ to a β-ketoacyl-CoA. The NADH that is produced interacts with the electron transport chain, generating ATP.

    • Enzyme: L-3-hydroxyacyl-CoA dehydrogenase.

  • The bond between the alpha and beta carbons of the β-ketoacyl-CoA is cleaved by a thiolase that requires coenzyme A. Acetyl-CoA is produced from the two carbons at the carboxyl end of the original fatty acyl-CoA, and the remaining carbons form a fatty acyl-CoA that is two carbons shorter than the original.

    • Enzyme: β -ketothiolase

  • The shortened fatty acyl-CoA repeats these four steps. Repetitions continue until all the carbons of the original fatty acyl-CoA are converted to acetyl-CoA.

Outcome of B Oxidation of Fatty Acids:

  1. When one palmitoyl-CoA is oxidized, 7 FADH2, 7 NADH, and 8 acetyl-CoA are formed.

    1. The 7 FADH2 each generate approximately 1.5 ATP, for a total of about 10.5 ATP.

    2. The 7 NADH each generate about 2.5 ATP, for a total of about 17.5 ATP.

    3. The 8 acetyl-CoA can enter the TCA cycle, each producing about 10 ATP, for a total of about 80 ATP.

    4. From the oxidation of palmitoyl-CoA to CO2 and H2O, a total of about 108 ATP are produced.

  2. The net ATP produced from palmitate that enters the cell from the blood is about 106 because palmitate must undergo activation (a process that requires the equivalent of 2 ATP) before it can be oxidized (108 ATP − 2 ATP = 106 ATP).

  3. B Oxidation of Fatty Acids generates a net 106 ATPs.

Significance:

  • Produces huge amounts of energy.

Commonly asked questions.

  1. Discuss in detail Beta Oxidation of Palmitic Acid.

  2. Discuss in detail Beta Oxidation of Fatty Acids.

  3. Discuss in detail Beta Oxidation of Even Carbon Fattys Acids.

  4. Write a short note on Beta oxidation of fatty acids.
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