Fatty Acid Synthesis and Beta Oxidation

Study Notes

Occurs in the cytosol of adipose tissue and liver
Key enzyme: fatty acid synthase (FAS)
Acetyl-CoA is the primary building block
Fatty acid synthesis is inhibited by:
- High levels of ATP, NADH, and acetyl-CoA
- Insulin
Activated by:
- Insulin
- Citrate (activates acetyl-CoA carboxylase)
- High glucose levels

Occurs in the mitochondria
Breakdown of fatty acids into acetyl-CoA
Four main steps:
1. Activation of fatty acids into acyl-CoA
2. Transport of acyl-CoA into the mitochondria
3. Beta oxidation (repative cycle of 4 reactions)
4. Electron transport chain and ATP synthesis
Inhibited by:
- Malonyl-CoA (product of fatty acid synthesis)
- ATP and NADH
Activated by:
- Low glucose levels
- High glucagon levels
- Epinephrine

Triglycerides (TG) are formed by esterifying glycerol with three fatty acids
TG are stored in adipose tissue and released into the bloodstream as free fatty acids (FFA) and glycerol
Hormone-sensitive lipase (HSL) is the key enzyme in TG breakdown
TG metabolism is regulated by:
- Insulin (inhibits TG breakdown, promotes synthesis)
- Glucagon and epinephrine (activate TG breakdown)
Lipoprotein lipase (LPL) breaks down TG in chylomicrons and VLDL in the bloodstream

Cholesterol is synthesized from acetyl-CoA in the liver
Key enzyme: HMG-CoA reductase
Cholesterol regulation is critical for maintaining proper membrane fluidity and function
Regulation of cholesterol synthesis:
- Inhibited by:
  - High cholesterol levels
  - Insulin
- Activated by:
  - Low cholesterol levels
  - Thyroid hormone
  - SREBP (sterol regulatory element-binding protein)
LDL receptors regulate cholesterol uptake in the liver and peripheral tissues

Occurs in the mitochondria
Breaks down fatty acids into acetyl-CoA
Consists of four main steps: activation of fatty acids, transport of acyl-CoA, beta oxidation, and electron transport chain and ATP synthesis
Inhibited by malonyl-CoA, ATP, and NADH
Activated by low glucose levels, high glucagon levels, and epinephrine

Triglycerides are formed by esterifying glycerol with three fatty acids
Stored in adipose tissue and released into the bloodstream as free fatty acids and glycerol
Hormone-sensitive lipase (HSL) is the key enzyme in triglyceride breakdown
Regulated by insulin, which inhibits triglyceride breakdown and promotes synthesis
Glucagon and epinephrine activate triglyceride breakdown
Lipoprotein lipase (LPL) breaks down triglycerides in chylomicrons and VLDL in the bloodstream

Synthesized from acetyl-CoA in the liver
Key enzyme: HMG-CoA reductase
Regulation is critical for maintaining proper membrane fluidity and function
Inhibited by high cholesterol levels and insulin
Activated by low cholesterol levels, thyroid hormone, and SREBP (sterol regulatory element-binding protein)
LDL receptors regulate cholesterol uptake in the liver and peripheral tissues