9: Beta oxidation of fatty acids | Lipid Metabolism-9 | Biochemistry | N'JOY Biochemistry

Summary

This video provides an in-depth explanation of beta oxidation of fatty acids, detailing the process of fatty acid breakdown in mitochondria. The video covers the three main stages: activation of fatty acids, transport into mitochondria via the carnitine shuttle, and the four-step beta oxidation cycle. It also explores the energetics, highlighting how ATP is generated from the process, with an example using palmitic acid. Additionally, the video explains the regulation of beta oxidation, emphasizing the role of key enzymes and hormonal control during different metabolic states such as fasting and feeding.

Takeaways

• 😀 Beta oxidation of fatty acids is the primary pathway for breaking down fatty acids into acetyl-CoA, generating energy during fasting, starvation, and diabetes.
• 😀 The process is called beta oxidation because the oxidation and splitting of two-carbon units occurs at the beta carbon atom of the fatty acid chain.
• 😀 The first stage of beta oxidation is the activation of fatty acids in the cytosol, where fatty acids are converted to acyl-CoA using ATP and magnesium.
• 😀 The second stage involves the transport of acyl-CoA into the mitochondria via the carnitine shuttle system, as acyl-CoA cannot directly pass through the mitochondrial membrane.
• 😀 Beta oxidation occurs in the mitochondria and consists of four reactions: dehydrogenation, hydration, second dehydrogenation, and cleavage, resulting in the release of acetyl-CoA.
• 😀 Dehydrogenation of fatty acyl-CoA produces FADH2, which is later oxidized to generate ATP in the electron transport chain.
• 😀 The hydration step adds water to the alpha-beta unsaturated fatty acid to form beta-hydroxy fatty acid, which is further dehydrogenated to form beta-keto fatty acid.
• 😀 Cleavage by the enzyme thiolase splits the beta-keto fatty acid into two-carbon acetyl-CoA and a shortened fatty acyl-CoA, which continues the cycle.
• 😀 The energetics of beta oxidation result in the generation of ATP through NADH and FADH2, with 106 ATP produced from the oxidation of palmitic acid, after accounting for activation energy costs.
• 😀 The rate of beta oxidation is regulated by malonyl-CoA, which inhibits the carnitine acyl transferase 1 enzyme in the fed state, and by hormones like glucagon and epinephrine during fasting, which promote beta oxidation.

Q & A

What is beta oxidation of fatty acids?

Beta oxidation is the process by which fatty acids are broken down in the mitochondria to produce acetyl-CoA, NADH, and FADH2. It occurs in three main stages: activation of fatty acids, transport into mitochondria, and oxidation inside the mitochondria.

Why is it called beta oxidation?

It is called beta oxidation because the oxidation and splitting of fatty acids occur at the beta carbon atom, which is the third carbon in the fatty acid chain.

What happens during the activation of fatty acids?

During activation, fatty acids are converted into acyl-CoA in the cytosol, a process that requires ATP and is facilitated by the enzyme acyl-CoA synthetase. This is the only step in beta oxidation that requires ATP.

Why can't acyl-CoA directly enter the mitochondria?

Acyl-CoA cannot directly cross the inner mitochondrial membrane. It must first be converted into acylcarnitine by the enzyme carnitine acyltransferase I, which can then be transported into the mitochondria.

What role does the carnitine shuttle system play in beta oxidation?

The carnitine shuttle system is responsible for transporting acyl-CoA into the mitochondria. It transfers the acyl group from acyl-CoA to carnitine, forming acylcarnitine, which can cross the mitochondrial membranes. Once inside, acyl-CoA is regenerated and undergoes oxidation.

What are the main steps of oxidation in the mitochondria?

In the mitochondria, acyl-CoA undergoes four main steps: dehydrogenation (producing FADH2), hydration (adding water to form beta-hydroxyacyl-CoA), dehydrogenation again (producing NADH), and cleavage (which generates acetyl-CoA and shortens the fatty acyl-CoA by two carbon atoms).

How much ATP is produced from the complete oxidation of palmitic acid?

The oxidation of one molecule of palmitic acid (C16) generates 8 acetyl-CoA, 7 NADH, and 7 FADH2. This yields a total of 108 ATP, minus the 2 ATP used for activation, giving a net yield of 106 ATP.

How is beta oxidation regulated in the body?

Beta oxidation is primarily regulated by the enzyme carnitine acyltransferase I, which controls the entry of acyl-CoA into the mitochondria. It is inhibited by malonyl-CoA, a product of fatty acid synthesis. Additionally, insulin and glucagon regulate beta oxidation by affecting the levels of malonyl-CoA.

How does insulin affect beta oxidation?

In the fed state, insulin promotes fatty acid synthesis and inhibits beta oxidation by increasing malonyl-CoA levels. Malonyl-CoA inhibits carnitine acyltransferase I, preventing the transport of acyl-CoA into the mitochondria and thus reducing beta oxidation.

How does glucagon promote beta oxidation during fasting?

During fasting, glucagon activates lipolysis, leading to the breakdown of triacylglycerol into fatty acids. These fatty acids are converted into acyl-CoA and transported into the mitochondria for beta oxidation. Glucagon also lowers malonyl-CoA levels, removing the inhibition on carnitine acyltransferase I and allowing beta oxidation to proceed.