Fatty Acids, Beta-Oxidation, and Lipid Metabolism: Key Concepts and Pathways

Describe the general structure of a fatty acid.

polar, hydrophilic carboxyl head group attached to a long, nonpolar, hydrophobic hydrocarbon tail.

What are the structural characteristics of most naturally occurring fatty acids?

even number of carbon atoms and exist in the cis-unsaturated configuration

How do length and saturation affect the physical properties of fatty acids?

ncreased chain length increases the melting point (more Van der Waals interactions). Increased saturation (fewer double bonds) also increases the melting point, making them more solid at room temperature. Cis-unsaturation introduces "kinks" that prevent tight packing, lowering the melting point.

What is the difference between omega and Delta nomenclature?

Delta counting starts from the carboxyl end (C1); omega counting starts from the terminal methyl end of the carbon chain.

What is the structure and primary purpose of Triacylglycerols (TAGs)?

They consist of a glycerol backbone esterified to three fatty acids. Their primary purpose is long-term energy storage.

Why are TAGs more energy-dense than carbohydrates?

Fatty acids are more highly reduced than carbohydrates, meaning they yield more energy upon oxidation, and they are stored in anhydrous (water-free) form, saving space and weight beta-Oxidation Pathway

What is the purpose of the "fatty acid activation" step?

It traps the fatty acid in the cell and prepares it for catabolism by attaching it to Coenzyme A (CoA) to form fatty acyl-CoA, consuming 2 ATP equivalents.

What is the role of the carnitine shuttle?

It transports long-chain fatty acyl-CoA across the inner mitochondrial membrane, where $\beta$-oxidation occurs.

What are the four steps of each beta-oxidation cycle?

1. Oxidation (by FAD)

2. Hydration

3. Oxidation (by NAD+)

4. Thiolysis (cleavage by CoA).

What are the products of a single cycle of $\beta$-oxidation?

1 Acetyl-CoA, 1 FADH2, 1 NADH, and the acyl chain shortened by two carbons.

What is the fate of odd-chain fatty acids during $\beta$-oxidation?

They undergo beta-oxidation until the final three-carbon fragment, propionyl-CoA, is produced, which is then converted into succinyl-CoA to enter the TCA cycle.Fatty Acid (FA) Synthesis

Compare and contrast FA synthesis and $\beta$-oxidation.

Location: Synthesis in cytosol- Oxidation in mitochondria.

Carrier: Synthesis uses Acyl Carrier Protein (ACP): Oxidation uses CoA.

Co-factors: Synthesis uses NADPH; Oxidation uses NAD+/FAD.

Regulation: Malonyl-CoA inhibits entry into the mitochondria (CPT1), preventing simultaneous synthesis and breakdown.

What is the rate-limiting enzyme in FA synthesis?

Acetyl-CoA carboxylase, which converts Acetyl-CoA to Malonyl-CoA.

What is a decarboxylative Claisen condensation?

It is the mechanism by which Malonyl-ACP and Acetyl-ACP condense; the loss of CO2 from the malonyl group provides the thermodynamic driving force for the reaction.HMG-CoA Pathways

Why is HMG-CoA considered a "central intermediate"?

It is the branch point where the pathway leads either to the synthesis of ketone bodies (in the liver) or cholesterol (in various tissues/liver).

What are the three ketone bodies, and why are they produced in the liver?

Acetoacetate, beta-hydroxybutyrate, and acetone. The liver produces them during fasting/starvation to provide an alternative fuel source for extrahepatic tissues (like the brain) when glucose is scarce.

What is the rate-limiting enzyme for cholesterol synthesis?

HMG-CoA reductase

What are the three major stages of cholesterol synthesis?

1. Synthesis of isoprene units (mevalonate pathway)

2. Condensation to form the linear molecule squalene

3. Cyclization (ring closure) and modification to form the steroid nucleus.

How is cholesterol synthesis regulated?

Through allosteric control (by mevalonate/cholesterol), post-translational degradation of HMG-CoA reductase, and transcriptional regulation (via SREBP).Eicosanoids

What are the three major classes of eicosanoids?

Prostaglandins, Thromboxanes, and Leukotrienes.

What are the general physiological roles of eicosanoids?

They act as localized signaling molecules (paracrine/autocrine) involved in inflammation, pain perception, fever induction, and blood clotting.

How do NSAIDs affect eicosanoid production?

NSAIDs (like aspirin or ibuprofen) inhibit Cyclooxygenase (COX) enzymes, preventing the conversion of arachidonic acid into prostaglandins and thromboxanes, thereby reducing inflammation and pain.