Lipid Metabolism and Fatty Acid Oxidation

Lipid Metabolism

• Lipid Transport: Lipoproteins transport lipids.
• Lipoproteins: Different lipoproteins have varying sizes, densities, protein content, and lipid compositions.
• Chylomicrons: Largest and least dense, transport dietary lipids.
• VLDL (Very-low-density lipoproteins): Transport lipids from liver to tissues.
• IDL (Intermediate-density lipoproteins): Formed from VLDL, transport lipids to tissues.
• LDL (Low-density lipoproteins): Transport cholesterol to peripheral tissues.
• HDL (High-density lipoproteins): Collect cholesterol from peripheral tissues and return it to the liver.
• Atherosclerosis: Atherosclerosis results in the thickening of artery walls, due to an atherosclerotic plaque.

Fatty Acid Oxidation

• Fatty Acid Oxidation: A series of reactions required to oxidize fatty acids.
• Triacylglycerols: The primary source of fatty acids. Hydrolysis separates the fatty acids from the glycerol backbone.
• Fatty Acid Activation: A two-step reaction catalyzed by acyl-CoA synthetase. Involves acyladenylate formation and transfer to CoA.
• Carnitine Shuttle: Acyl groups cross the inner mitochondrial membrane via the carnitine shuttle system. (Carries fatty acids into the mitochondria for oxidation)
• β-Oxidation: A spiral process where 7 rounds of β-oxidation degrade a C16 fatty acid to 8 acetyl-CoA molecules.
• Oxidation Steps: Successive removal of 2-carbon acetyl units from a fatty acyl chain.

Lipid Metabolism in Context

• Pathways: Key pathways include those for lipid synthesis and degradation.

Triacylglycerol Breakdown

• Hydrolysis: Hydrolysis breaks down triacylglycerols into glycerol and fatty acids.

Fatty Acid Activation

• Acyl-CoA Synthetase: Catalyzes the two-step activation of fatty acids.

The Carnitine Shuttle

• Transport mechanism: Carnitine carries activated fatty acids into the mitochondria for oxidation.

β-Oxidation Steps

• Electron transfer reactions: Involved in transferring electrons from the acyl group to electron carriers.
• Addition of water: Adds water across the double bond.
• NAD+ Cofactor: Oxidizes the 3-hydroxyacyl-CoA.
• Release of Acetyl-CoA: Removal of acetyl groups from the fatty acid chain.

β Oxidation Results

• ATP production: One round of β-oxidation results in 14 ATP.

Fatty Acids with cis Double Bonds

• Problem in oxidation: Cis double bonds pose problems for enzymes in β-oxidation.
• Specific round: Problems begin at specific rounds during β-oxidation.

Enoyl-CoA Isomerase Reaction

• Isomerization: Converts a specific cis double bond to a trans double bond.

Degradation of Unsaturated Fatty Acids

• Less free energy: Unsaturated fatty acids yield less free energy than saturated fatty acids.

Oxidation of Odd-Chain Fatty Acids

• Intermediate: Oxidation yields Propionyl-CoA.

Catabolism of Propionyl-CoA

• Carboxylation: Adds a carboxyl group to propionyl-CoA.
• Racemization: Interconverts the stereoisomers.
• Rearrangement: Reaches succinyl-CoA.

Breakdown of Propionyl-CoA

• Succinyl-CoA. A citric acid cycle intermediate.
• Malate. Produced by reactions 5-7 of citric acid cycle.

A Cobalamin-Derived Cofactor

• Nucleotides. Contains nucleotides.

Peroxisomes

• Structure: Enclosed by a single membrane.
• Enzyme content: Contain degradative and biosynthetic enzymes.

Fatty Acid Oxidation in Peroxisomes

• Enoyl-CoA product: Identical to the product of mitochondrial acyl-CoA dehydrogenase.

Peroxisomes and Mitochondrial Enzymes

• Unique role: Break down fatty acids unrecognized by mitochondrial enzymes.

Fatty Acid Synthesis

• Acyl Carrier Protein (ACP): Part of the fatty acid synthesis process.
• Coenzyme A (CoA): Another important coenzyme in fatty acid synthesis.

Fatty Acid Synthesis: Repetition

• High energy yield: Fatty acid synthesis requires less energy compared to fatty acid oxidation.

Condensation in Fatty Acid Synthesis

• Acetyl Thioester Group: Identified in the condensation process.

Other Enzymes

• Elongation and desaturation: Enzymes for elongation and desaturation reactions.

Control of Fatty Acid Metabolism

• Regulation points: Key control points in lipid metabolism.

Ketogenesis

• Ketone body formation: Somewhat similar to fatty acid synthesis or oxidation.

Catabolism of Ketone Bodies

• Oxidation: Oxidation of ketone bodies.
• Succinyl-CoA: Donates CoA group to produce acetoacetyl-CoA.
• Thiolase: Cleaves the 4 carbon unit to acetyl-CoA molecules.

Synthesis of Other Lipids

• Triacylglycerols, phospholipids, and cholesterol: Synthesis outlined - Triacylglycerols from glycerol-3-phosphate + fatty acids. Phospholipids, similar to triacylglycerols, with added phosphate groups and nitrogenous bases. Cholesterol synthesis starts with HMG-CoA.

Glycerol-3-Phosphate Dehydrogenase Reaction

• Importance: Phosphorylated glycerol and glycolytic intermediates play a crucial role.

Triacylglycerol Synthesis

• The reactions leading to the synthesis of triacylglycerols.

Phospholipid Synthesis

• ATP-dependent reactions: Phosphorylates the OH group of ethanolamine or choline.
• CTP-dependent reactions: CDP-intermediates are central to phospholipid synthesis.

Phosphatidylserine Synthesis

• Head-group exchange reaction: Exchange reaction to produce phosphatidylserine.

Phosphatidylinositol Synthesis

• CDP-diacylglycerol. Important in the synthesis pathway
• Inositol. Group replaces CMP for inositol synthesis.

Cholesterol Synthesis

• First Two Steps: Same as ketogenesis.
• 21 Reactions: 21 reactions convert squalene into cholesterol.

Cholesterol Storage

• Cholesteryl esters. Describe storage form of cholesterol.

Statins

• Mechanism: Lower serum cholesterol by blocking mevalonate synthesis.

SREBP Regulatory System

• Cholesterol Regulation: Coordinates cholesterol production and transport through the SREBP system.

Summary of Lipid Metabolism

• Overview: Important pathways and their relations are laid out.

This quiz covers the essential concepts of lipid metabolism, including lipid transport mechanisms and the roles of various lipoproteins such as chylomicrons, VLDL, LDL, and HDL. Additionally, it explores the process of fatty acid oxidation and its significance in energy production. Test your knowledge of these critical biochemical processes!