Fatty Acid Synthesis Pathway: Overview, Enzymes and Regulation

Summary

This video provides a detailed explanation of fatty acid synthesis, outlining its biochemical steps, regulation, and key molecules involved. Fatty acid synthesis occurs in the cytoplasm, primarily in the liver and adipose tissue, where acetyl-CoA and NADPH play crucial roles. The process begins with the conversion of acetyl-CoA to malonyl-CoA, followed by multiple cycles in the fatty acid synthase complex to form palmitate, a 16-carbon fatty acid. The synthesis is tightly regulated by factors such as insulin, citrate, and CHREBP, with energy consumption in the form of ATP and NADPH, and the production of byproducts like CO2.

Takeaways

• 😀 Fatty acids have a chemical structure consisting of a carboxylic acid group and a hydrocarbon chain, making them amphipathic, with both hydrophobic and hydrophilic properties.
• 😀 Fatty acid synthesis occurs in the cytosol, as opposed to fatty acid breakdown (beta oxidation), which happens in the mitochondria.
• 😀 Acetyl-CoA and NADPH are essential for fatty acid synthesis. Acetyl-CoA is primarily derived from citrate, while NADPH comes from the pentose phosphate pathway.
• 😀 The synthesis of fatty acids begins with acetyl-CoA, which is converted into malonyl-CoA by acetyl-CoA carboxylase, a critical and rate-limiting enzyme.
• 😀 The conversion of acetyl-CoA into malonyl-CoA requires biotin, ATP, and the enzyme acetyl-CoA carboxylase, which is regulated by factors like insulin and citrate.
• 😀 Malonyl-CoA serves as a two-carbon donor in the elongation of fatty acid chains, with each cycle adding two carbons to the growing chain.
• 😀 Fatty acid elongation occurs on the fatty acid synthase complex, which is responsible for repeating cycles of condensation, reduction, dehydration, and further reduction.
• 😀 The final product of fatty acid synthesis is palmitate, a saturated 16-carbon fatty acid, produced after seven cycles of elongation.
• 😀 Fatty acid synthesis is highly regulated by insulin, which activates acetyl-CoA carboxylase, and by palmitate, which inhibits the pathway via feedback regulation.
• 😀 The overall energy requirements for fatty acid synthesis include ATP for carboxylation of acetyl-CoA, NADPH for reductions, and the recycling of components like biotin and CO2.
• 😀 Fatty acid synthesis not only involves the creation of fatty acids but also contributes to energy storage in the form of triglycerides, which are stored in adipose tissue.

Q & A

What is a fatty acid and what are its main components?

A fatty acid is a molecule that contains a carboxylic acid group and a chain of hydrocarbons. The hydrocarbon chain gives the fatty acid its hydrophobic properties, while the carboxyl group is hydrophilic, making the fatty acid amphipathic, meaning it has both hydrophilic and hydrophobic regions.

Where does fatty acid synthesis occur in the body?

Fatty acid synthesis occurs in the cytosol, unlike fatty acid catabolism (beta-oxidation), which takes place in the mitochondria.

What is the role of acetyl-CoA in fatty acid synthesis?

Acetyl-CoA is a key molecule required for fatty acid synthesis. It is the starting substrate for the synthesis process and is needed in high amounts in the cytoplasm. Acetyl-CoA is transported from the mitochondria to the cytoplasm in the form of citrate.

How is acetyl-CoA transported from the mitochondria to the cytoplasm?

Acetyl-CoA cannot leave the mitochondria directly, so it is first converted into citrate, which is transported out of the mitochondria. Once in the cytoplasm, citrate is acted upon by ATP citrate lyase, converting it back into acetyl-CoA.

What is malonyl-CoA, and how is it formed?

Malonyl-CoA is a two-carbon donor used in the elongation of fatty acid chains. It is formed from acetyl-CoA through the enzymatic reaction catalyzed by acetyl-CoA carboxylase, which requires biotin, ATP, and results in the addition of a carboxyl group to acetyl-CoA.

What regulates the activity of acetyl-CoA carboxylase (ACC)?

Acetyl-CoA carboxylase is regulated by several factors. It is activated by insulin, citrate, and carbohydrate response element binding protein (ChREBP). It is inhibited by glucagon, epinephrine, palmitoyl-CoA, and AMP-activated protein kinase (AMPK), especially through phosphorylation.

What is the role of malonyl-CoA in fatty acid catabolism?

Malonyl-CoA acts as a negative regulator of fatty acid catabolism by inhibiting carnitine palmitoyltransferase 1 (CPT1), an enzyme involved in the transport of fatty acids into the mitochondria for beta-oxidation.

How does fatty acid synthase contribute to fatty acid synthesis?

Fatty acid synthase is a large enzyme complex that catalyzes the stepwise elongation of a fatty acid chain. It facilitates the transfer of acetyl groups and malonyl groups onto a growing chain, where each cycle adds two carbons to the chain, ultimately producing saturated fatty acids like palmitate.

How many cycles of the fatty acid synthase process are required to form palmitate?

Seven cycles of the fatty acid synthase process are required to form palmitate, a 16-carbon saturated fatty acid. Each cycle involves the addition of two carbons from malonyl-CoA, and the process continues until a 16-carbon chain is formed.

What are the energy requirements for fatty acid synthesis?

Fatty acid synthesis requires 7 ATP molecules for the formation of malonyl-CoA and 14 NADPH molecules for the reduction steps during each cycle of the fatty acid synthase process. Additionally, 7 carbon dioxide molecules are released as byproducts.