Fatty Acid Synthesis
Overview
- Fatty acid synthesis primarily occurs in the liver but can also occur in other tissues.
- Occurs in the fed state when blood glucose levels are high or cellular ATP levels are high.
- Main hormone regulating this process is insulin.
Key Concepts
Conditions Triggering Fatty Acid Synthesis
- Fed State: Eating and absorbing food.
- High Blood Glucose Levels.
- High Cellular ATP: Excess ATP production signals the body to store molecules for later use rather than breaking them down.
Initial Steps in Fatty Acid Synthesis
- Glucose enters the cell and is converted to pyruvate.
- Pyruvate is transported into the mitochondria and converted into acetyl-CoA.
- Acetyl-CoA combines with oxaloacetate to form citrate.
- Citrate can then be converted within the Krebs cycle to produce ATP.
- When ATP is in excessive amounts, it inhibits the enzyme isocitrate dehydrogenase, causing isocitrate to build up and convert back to citrate.
Role of Citrate
- Citrate can exit the mitochondria and be converted back to acetyl-CoA and oxaloacetate by a special enzyme called citrate lyase.
Key Enzymes and Processes
Citrate Lyase
- Converts citrate into oxaloacetate and acetyl-CoA.
- Requires coenzyme A (CoA) to form acetyl-CoA.
Acetyl-CoA Carboxylase (ACC)
- Converts acetyl-CoA into malonyl-CoA.
- Contains biotin as a coenzyme for the carboxylation reaction.
- Heavily regulated and exists in two forms: active (polymerized) and inactive (dimer).
- Regulated by both allosteric mechanisms (citrate stimulates, long-chain fatty acids inhibit) and hormones (insulin stimulates, glucagon/cortisol/epinephrine inhibit).
NADPH
- Important reducing agent required for fatty acid synthesis.
- Generated by Malic enzyme converting malate into pyruvate, providing NADPH for the process.
- Also produced in the pentose phosphate pathway.
Hormonal Regulation of ACC
- Insulin activates phospho-protein phosphatases which dephosphorylate ACC, converting it to its active form.
- Glucagon and epinephrine activate protein kinase A, which phosphorylates ACC, converting it to its inactive form.
Summary
- Acetyl-CoA carboxylase (ACC) is the central enzyme in fatty acid synthesis.
- Fatty acid synthesis is a highly regulated process that occurs when energy and substrate levels are abundant.
- Insulin promotes fatty acid synthesis, while glucagon and other stress hormones inhibit it.
- NADPH is crucial for the biosynthetic steps of fatty acid synthesis.
In the next lecture, we will discuss how the malonyl-CoA formed in this process serves as the building block for fatty acids.