Lecture Notes: Fatty Acid Synthesis

Introduction

• Fatty acid synthesis occurs primarily in the liver but can also happen in other tissues.
• This process occurs when blood glucose levels are high, particularly in a "fed state."
• High ATP levels can also trigger fatty acid synthesis.
• Main Hormone Involved: Insulin (stimulates fatty acid synthesis during high glucose levels).

Key Steps in Fatty Acid Synthesis

Starting Point: Glucose to Citrate

• Glucose enters the cell via glucose transporters.
• It is then converted to pyruvate, which enters the mitochondria.
• Pyruvate is converted to acetyl-CoA, which combines with oxaloacetate to form citrate.
• Citrate can convert back to isocitrate and further through the Krebs cycle to produce ATP.

Regulation in High ATP Conditions

• High ATP inhibits the enzyme isocitrate dehydrogenase.
• This leads to accumulation of isocitrate and subsequently citrate.
• Citrate exits the mitochondria and is converted by citrate lyase into acetyl-CoA and oxaloacetate.

Conversion to Fatty Acids

• Acetyl-CoA is converted to malonyl-CoA by the enzyme acetyl-CoA carboxylase (ACC).
  • This enzyme requires biotin as a coenzyme.
• Malonyl-CoA is crucial for fatty acid synthesis.
• NADPH is needed as a reducing agent, produced via the malic enzyme and the pentose phosphate pathway.

Regulation of Acetyl-CoA Carboxylase (ACC)

Allosteric Regulation

• Stimulated by citrate (indicates excess substrate for fatty acid synthesis).
• Inhibited by long-chain fatty acyl-CoA (indicates fatty acid oxidation preference).

Hormonal Regulation

• Insulin stimulates ACC, promotes the polymerization (activation) of ACC.
• Glucagon, epinephrine, and norepinephrine inhibit ACC by promoting its phosphorylation (inactivation).

Enzyme Activation/Inactivation

• ACC can exist in either:
  • Dimer (inactive) form: Phosphorylated by protein kinase A.
  • Polymer (active) form: Dephosphorylated by phosphoprotein phosphatases.
• Insulin promotes dephosphorylation (activation), while glucagon/epinephrine promotes phosphorylation (inactivation).

Conclusion

• Malonyl-CoA is the precursor for fatty acid chains.
• Next steps involve using these precursors to build fatty acids in subsequent pathways.
• Further details will be explored in the next video.