Metabolism | Fatty Acid Oxidation: Part 1

Name: Metabolism | Fatty Acid Oxidation: Part 1
Uploaded: 2017-05-30T17:56:00.000Z
Duration: 58 min 40 s

Fatty Acid Oxidation Overview

Introduction to Fatty Acid Oxidation

The video discusses fatty acid oxidation, building on previous content about fat mobilization, specifically the breakdown of triglycerides into glycerol and fatty acids.

Key tissues that utilize fatty acids for energy include heart muscle (myocardium), skeletal muscles, and the liver.

Importance of the Liver

The liver plays a crucial role in generating ketone bodies from fatty acids, which will be elaborated upon later in the discussion.

Transporting Fatty Acids into Cells

Long-chain fatty acids (approximately 16 carbons long) are introduced; palmitic acid is highlighted as a specific example.

The structure of a long-chain fatty acid is described, including its carboxy group and alpha/beta carbons.

Activation of Fatty Acids

To prevent free fatty acids from exiting the cell, they must be activated by an enzyme called fatty acyl-CoA synthetase.

This activation process requires energy derived from ATP, converting it to ADP and inorganic phosphate while attaching coenzyme A (CoA) to the fatty acid.

Formation of Fatty Acyl-CoA

The resulting product after activation is termed fatty acyl-CoA, which consists of the R group attached to CoA.

Despite being activated with CoA, this molecule cannot enter mitochondria directly due to its size and structure.

Role of Carnitine in Transport

To facilitate mitochondrial entry, carnitine attaches to the activated fatty acyl-CoA through a transporter mechanism.

This reaction results in releasing CoA and forming a new compound called fatty acyl-carnitine.

Conclusion on Transport Mechanism

Fatty Acid Activation and Transport Mechanisms

Overview of Fatty Acyl Carnitine

The molecule discussed is fatty acyl carnitine, which can easily exit through a bidirectional transporter known as translocase.

To prevent the fatty acyl carnitine from exiting, it must undergo a reaction where coenzyme A (CoA) is added back onto it after removing the carnitine.

Enzymatic Reactions Involved

An enzyme catalyzes the reaction by breaking the bond to remove carnitine and attaching CoA, resulting in a fatty acyl-CoA structure.

The removed carnitine is recycled back out into the cytosol after this enzymatic action.

Transport Mechanism

The transporter responsible for moving fatty acyl carnitine into the mitochondrial matrix is called Carnitine Acyl Transferase Type 1 (CAT1), also referred to as Carnitine Palmitoyl Transferase Type 1 (CPT1).

Once inside the mitochondrial matrix, another enzyme, Carnitine Acyl Transferase Type 2 (CAT2 or CPT2), acts on the fatty acyl-CoA to facilitate further reactions.

Steps of Fatty Acid Metabolism

The first step involves activating the fatty acid by adding CoA and converting ATP into ADP and inorganic phosphate; this process is catalyzed by Fatty Acyl-CoA Synthetase.

Following activation, transport occurs to move fatty acyl-CoA into mitochondria for beta oxidation.

Beta Oxidation Process

During beta oxidation, specific nomenclature identifies carbons: carbon one (α-carbon), carbon two (β-carbon), etc.

The initial step in beta oxidation involves removing hydrogens from specific carbons using FAD, forming FADH₂ through an enzyme called Acyl-CoA Dehydrogenase.

Understanding the Steps of Beta-Oxidation

Step 1: Initial Reaction with Coenzyme A

The process begins with oxygen bound to coenzyme A, indicating the first step in beta-oxidation is initiated.

Step 2: Hydration of Enoyl-CoA

Water is added across a double bond in the molecule, requiring an enzyme for hydration.

The enzyme facilitating this reaction is called enoyl-CoA hydratase, which helps convert the substrate into a specific form known as enoyl-CoA.

Step 3: Formation of Trans Delta 2-Enoyl-CoA

The resulting structure from hydration has trans configuration due to hydrogen atoms being on opposite sides of the double bond, denoted as trans Delta 2-enoyl-CoA.

This molecule undergoes further reactions where water addition results in structural changes leading to beta-hydroxy acyl-CoA.

Step 4: Conversion to Beta-Hydroxy Acyl-CoA

After adding water, the double bond disappears and transforms into a hydroxyl group on the beta carbon, forming beta-hydroxy acyl-CoA.

Step 5: NAD+ Reduction and Ketone Formation

In this step, NAD+ is reduced to NADH by taking up hydride ions from the substrate.

This reduction leads to a rearrangement that forms a ketone group at the beta carbon position, resulting in beta-keto acyl-CoA.

Final Steps and Enzyme Involvement

The enzyme responsible for converting beta-hydroxy acyl-CoA into beta-keto acyl-CoA is identified as beta-keto acyl-CoA dehydrogenase.

Understanding the Role of THAS Enzyme in Fatty Acid Metabolism

Functionality of THAS Enzyme

The THAS enzyme is crucial for a specific reaction involving fatty acids, particularly focusing on the cleavage between alpha and beta carbons.

The primary goal of this step is to break the bond between the alpha and beta carbon, which leads to significant metabolic changes.

Products Generated from Reaction

Upon cleaving the bond, two products are formed: one being acetyl CoA and another product that involves adding coenzyme A to the beta carbon.

The resulting structure includes a new fatty acyl CoA, which will be recycled for further rounds of beta oxidation.

Importance of Beta Oxidation

Beta oxidation refers to breaking down fatty acids by cleaving bonds between alpha and beta carbons, releasing acetyl CoA as a key product.

Each cycle reduces the length of the fatty acid chain by two carbons, allowing it to undergo multiple rounds until fully metabolized.

Acetyl CoA's Role in Energy Production

Acetyl CoA can enter the Krebs cycle where it generates NADH, FADH2, and ATP through subsequent reactions.

This process is vital when glucose levels are low; fats become an alternative energy source through their conversion into acetyl CoA.

Overall Significance of Beta Oxidation Process

The main purpose of beta oxidation is to produce two-carbon fragments (acetyl CoA), essential for energy production during fasting or low carbohydrate intake.

For a 16-carbon fatty acid undergoing beta oxidation, eight molecules of acetyl CoA can be produced along with significant amounts of NADH and FADH2.

Rounds of Beta Oxidation Explained

Understanding Beta Oxidation of Fatty Acids

Overview of Carbon Fragmentation

The speaker illustrates the process of cutting a 16-carbon fatty acid into smaller fragments, labeling the first carbon as "number one" and the last as "16."

The fragmentation involves making seven cuts to create carbon fragments, emphasizing that each cut divides larger segments into smaller two-carbon units.

Calculating Rounds of Beta Oxidation

The speaker explains how to determine the number of rounds of beta oxidation for an 18-carbon fatty acid by subtracting one from half the total number of carbons (acetyl CoA produced).

For a 26-carbon fatty acid, dividing by two yields 13 acetyl CoAs; subtracting one results in 12 rounds of beta oxidation.

Upcoming Topics on Energy Yield

Future discussions will cover energy yield from beta oxidation and address odd-chain fatty acids.