Metabolism | Fatty Acid Synthesis: Part 1

Summary

This video delves into the process of fatty acid synthesis, focusing primarily on the liver, though it can occur in other tissues. The synthesis is triggered when blood glucose levels are high or cellular ATP levels are elevated. Key enzymes such as citrate lyase and acetyl CoA carboxylase play crucial roles in the process. The video also explores hormonal regulation by insulin and the opposing effects of cortisol and glucagon, alongside allosteric regulators like citrate and long-chain fatty acids. NADPH generation from pathways like the pentose phosphate pathway is highlighted as a key contributor to the synthesis process.

Takeaways

• 😀 Fatty acid synthesis primarily occurs in the liver but can happen in other tissues during the fed state when blood glucose levels are high or when there is excessive ATP production.
• 😀 Insulin is the main hormone that stimulates fatty acid synthesis, as it is released when blood glucose levels are high.
• 😀 High ATP production can signal the body to store molecules rather than break them down, contributing to the regulation of fatty acid synthesis.
• 😀 Glucose is first converted to pyruvate, then to acetyl-CoA, which combines with oxaloacetate to form citrate as part of the citric acid cycle.
• 😀 When ATP levels are high, ATP inhibits the enzyme isocitrate dehydrogenase, leading to the accumulation of citrate, which can then leave the mitochondria and participate in fatty acid synthesis.
• 😀 Citrate is broken down into oxaloacetate and acetyl-CoA by the enzyme citrate lyase, which is essential for initiating fatty acid synthesis.
• 😀 Acetyl-CoA carboxylase (ACC) is a key enzyme in fatty acid synthesis that catalyzes the conversion of acetyl-CoA to malonyl-CoA, a crucial precursor for fatty acids.
• 😀 Biotin is an essential coenzyme for acetyl-CoA carboxylase, facilitating the addition of a carbon to acetyl-CoA, turning it into malonyl-CoA.
• 😀 Acetyl-CoA carboxylase activity is regulated by both allosteric effectors (such as citrate and long-chain fatty acids) and hormonal signals like insulin, glucagon, and epinephrine.
• 😀 The enzyme acetyl-CoA carboxylase exists in two forms: inactive dimers and active polymerized forms. Citrate and insulin promote polymerization, activating the enzyme for fatty acid synthesis.
• 😀 Glucagon, epinephrine, and norepinephrine trigger protein kinase A, which phosphorylates and inactivates acetyl-CoA carboxylase, inhibiting fatty acid synthesis under fasting conditions.

Q & A

What is the primary hormone responsible for regulating fatty acid synthesis?

The primary hormone responsible for regulating fatty acid synthesis is insulin. It is released when blood glucose levels are high, signaling the body to start synthesizing fatty acids.

What state of metabolism triggers fatty acid synthesis?

Fatty acid synthesis occurs during the 'fed state,' which happens after eating, when blood glucose levels are high, or when there is an excess of ATP in the body.

How does acetyl-CoA enter the process of fatty acid synthesis?

Acetyl-CoA is formed from pyruvate in the mitochondria. It then combines with oxaloacetate to form citrate, which can be broken down into acetyl-CoA again, the key precursor for fatty acid synthesis.

What role does citrate play in fatty acid synthesis?

Citrate plays a crucial role in fatty acid synthesis by being converted back into acetyl-CoA and oxaloacetate in the cytoplasm, which then feeds into the acetyl-CoA carboxylase pathway to form malonyl-CoA, the key intermediate for fatty acid synthesis.

What is the function of the enzyme acetyl-CoA carboxylase in fatty acid synthesis?

Acetyl-CoA carboxylase catalyzes the conversion of acetyl-CoA into malonyl-CoA, a key intermediate in the synthesis of fatty acids. This enzyme is highly regulated by both allosteric and hormonal mechanisms.

How is acetyl-CoA carboxylase regulated?

Acetyl-CoA carboxylase is regulated both allosterically and hormonally. Citrate and insulin activate it, promoting fatty acid synthesis, while long-chain fatty acids and glucagon inhibit it, signaling the body to stop fat synthesis and start fat breakdown.

What is the role of NADPH in fatty acid synthesis?

NADPH provides the necessary reducing power for the synthesis of fatty acids. It is generated by the malate enzyme and the pentose phosphate pathway, which are crucial for driving the reactions of fatty acid synthesis.

How do long-chain fatty acids inhibit fatty acid synthesis?

Long-chain fatty acids inhibit fatty acid synthesis by binding to acetyl-CoA carboxylase and promoting its inactive dimeric form, signaling that the body has sufficient fat and should halt the synthesis of more.

What effect does insulin have on acetyl-CoA carboxylase?

Insulin activates acetyl-CoA carboxylase by promoting its polymerization into an active form, stimulating the conversion of acetyl-CoA into malonyl-CoA and initiating fatty acid synthesis.

What is the significance of the pentose phosphate pathway in fatty acid synthesis?

The pentose phosphate pathway is significant because it generates NADPH, which is essential for the reduction steps in fatty acid synthesis. It provides additional NADPH beyond what is produced by the malate enzyme.