Study Notes: Fatty Acid Oxidation and Metabolism

Fatty Acid Oxidation and Metabolism

Introduction to Fatty Acid Oxidation

Fatty acid oxidation is a central metabolic process in which fatty acids are broken down to generate energy. This process involves several steps and key intermediates, ultimately linking to the Citric Acid Cycle for complete oxidation and ATP production.

Entry of Glycerol into Central Metabolism

• Glycerol is a product of fat (triacylglycerol) breakdown.

• It enters central metabolism as dihydroxyacetone phosphate (DHAP), which is an intermediate in glycolysis and gluconeogenesis.

• Equation: $\text{Glycerol} \xrightarrow{glycerol kinase} \text{Glycerol-3-phosphate} \xrightarrow{glycerol-3-phosphate dehydrogenase} \text{DHAP}$

• Application: DHAP can be converted to glyceraldehyde-3-phosphate and enter glycolysis.

Carnitine and Fatty Acid Transport

Carnitine is essential for the transport of long-chain fatty acids into the mitochondria, where β-oxidation occurs.

• Carnitine binds to fatty acyl groups to form acyl-carnitine, which is transported across the mitochondrial membrane.

• Key Step: Carnitine shuttle enables the entry of fatty acids into the mitochondrial matrix.

• Equation: $\text{Fatty acyl-CoA} + \text{Carnitine} \rightarrow \text{Acyl-carnitine} + \text{CoA}$

• Application: Without carnitine, long-chain fatty acids cannot be oxidized efficiently.

Control of Enzymes in β-Oxidation

β-Oxidation is regulated by several key enzymes, which control the rate and efficiency of fatty acid breakdown.

• Acyl-CoA dehydrogenase catalyzes the first step in β-oxidation.

• Enoyl-CoA hydratase adds water to the trans double bond.

• Hydroxyacyl-CoA dehydrogenase oxidizes the hydroxyl group to a keto group.

• Thiolase cleaves the β-ketoacyl-CoA to release acetyl-CoA.

• Example: The enzyme acyl-CoA dehydrogenase is often the rate-limiting step in β-oxidation.

ATP Yield from Fatty Acid Oxidation

The complete oxidation of fatty acids through β-oxidation and the Citric Acid Cycle yields significant amounts of ATP.

• Palmitic acid (C16:0) is a common example used to illustrate ATP yield.

• Each round of β-oxidation produces 1 FADH2, 1 NADH, and 1 acetyl-CoA.

• Acetyl-CoA enters the Citric Acid Cycle, generating additional NADH, FADH2, and GTP/ATP.

• Equation: $\text{Total ATP from palmitate} \approx 106$

• Example: The oxidation of one palmitic acid molecule yields approximately 106 ATP molecules.

Summary Table: ATP Yield from Fatty Acid Oxidation

Fatty Acid	Number of Carbons	ATP Yield
Palmitic acid	16	106
Stearic acid	18	120
Lauric acid	12	80
Additional info: ATP yield may vary slightly depending on shuttle and transport costs.

Additional info:

• Fatty acid oxidation is tightly regulated by hormonal signals (e.g., insulin inhibits, glucagon stimulates).

• Defects in carnitine transport or β-oxidation enzymes can lead to metabolic diseases.