Triacylglycerol and Cholesterol Metabolism

Triacylglycerol Metabolism

• Acyl-CoA synthetase catalyzes the synthesis of acyl-CoA from fatty acids.
• Acyl-CoA acyltransferase is involved in the formation of triacylglycerols (TAG) from glycerol-3-phosphate.
• Lipases hydrolyze triacylglycerols to release fatty acids and glycerol for energy metabolism.
• Glycerol-3-phosphate is derived from glucose via glycolysis.

Formation of Triacylglycerols

• Acyl-CoA reacts with glycerol-3-phosphate to form phosphatidic acid, an intermediate in lipid synthesis.
• Phosphatidic acid is converted to diacylglycerol (DAG) through the action of a phosphatase.
• DAG can further react with acyl-CoA to form triacylglycerol, the main storage form of lipids.

Cholesterol Metabolism

• Acyl-CoA cholesterol acyltransferase (ACAT) converts free cholesterol into cholesteryl esters, making it hydrophobic for easier storage within lipoproteins.
• Cholesteryl esters constitute approximately 70% of the cholesterol found in plasma lipoproteins.

Regulation of Cholesterol Biosynthesis

• Cholesterol synthesis is regulated hormonally and transcriptionally at the level of HMG-CoA reductase.
• Insulin activates HMG-CoA reductase through dephosphorylation, promoting cholesterol synthesis.
• Glucagon inhibits HMG-CoA reductase by promoting its phosphorylation, reducing cholesterol synthesis.

Fatty Acid Synthesis

• Fatty acid synthesis begins with the formation of malonyl-CoA from acetyl-CoA, a reaction catalyzed by acetyl-CoA carboxylase.
• The first step in fatty acid chain elongation is the condensation of acetyl groupt and malonyl group with the release of CO2.

Fatty Acid Oxidation

• Glucagon promotes the mobilization of fatty acids from triacylglycerol stores for energy, while insulin aids in their synthesis.
• Malonyl-CoA inhibits carnitine acyltransferase I (CPT I), preventing fatty acid entry into mitochondria during high carbohydrate intake.
• β-oxidation in mitochondria breaks down fatty acids to generate acetyl-CoA for energy production.

Coordination of Fatty Acid Metabolism

• High carbohydrate meals stimulate insulin release, leading to enhanced fatty acid synthesis and reduced degradation.
• Insulin activates ACC, which produces malonyl-CoA, inhibiting CPT I and subsequently β-oxidation, focusing on lipid storage rather than degradation.

Key Enzymes and Processes

• ACAT: Catalyzes transfer of fatty acids to cholesterol.
• HMG-CoA reductase: Central to cholesterol biosynthesis, regulated by hormonal signals.
• Acetyl-CoA Carboxylase: Regulates the first step of fatty acid synthesis.
• Protein phosphatase 1: Activates ACC, linking insulin signaling to lipid metabolism.

This quiz covers key aspects of triacylglycerol and cholesterol metabolism, including the roles of acyl-CoA synthetase, lipases, and the formation of triacylglycerols from glycerol-3-phosphate. It also explores the conversion of free cholesterol into cholesteryl esters for storage. Test your knowledge on these vital biochemical processes!