Lipids & Lipid Catabolism Flashcards
Lipid Digestion Overview
Digestion Site: Lipids are digested at the lipid-water interface.
Rate Determinant: Digestion rate depends on the surface area of the interface.
Bile Acids: Secreted into the small intestine, increasing surface area through detergent activities.
Role of Bile Acids
Function: Bile acids increase lipid-water surface area.
Mechanism: Detergent activities induce formation of lipid micelles.
Location: Bile acids are secreted into the small intestine for digestion.
Triacylglyceride Degradation
Process: Triacylglycerides broken down by lipases.
Pancreatic Lipase: Catalyzes sequential hydrolysis of triacylglycerols.
Products: Generates free fatty acids and 2-monoglyceride.
Phospholipid Degradation
Pancreatic Phospholipase A2: Degrades phospholipids.
Cleavage: Cleaves C2 fatty acid, yielding lysophospholipids.
Detergent Nature: Lysophospholipids act as detergents, emulsifying fat similar to bile acids.
Lipolysis Process in Adipose Cells
Definition: Lipolysis is the process of releasing fatty acids from triacylglycerols stored in adipose cells.
Regulation: Hormone-dependent, primarily regulated by adrenaline (epinephrine).
Hormone Action: Adrenaline activates G-protein, leading to cyclic AMP (cAMP) production through adenyl cyclase.
Protein Kinase A (PKA) Activation
cAMP Activation: Increasing cAMP levels activate Protein Kinase A (PKA).
PKA Substrates: PKA targets glycogen phosphorylase kinase, perilipin, and hormone-sensitive triacylglycerol lipase.
Perilipin Function: Phosphorylation of perilipin by PKA opens lipid droplets, allowing lipase access.
Lipase Activation
Hormone-Sensitive Lipase (HSL): Activated by PKA phosphorylation.
Triacylglycerol Breakdown: HSL degrades triacylglycerols into fatty acids.
Perilipin Role: Phosphorylation of perilipin facilitates access for lipase to lipid droplet.
Fatty Acid Transport and Utilization
Fatty Acid Release: Fatty acids are released from adipocytes.
Transport: Fatty acids bind to serum albumin in the blood for solubilization and transport.
Target Tissues: Fatty acids enter target tissues via specific transporters for energy production.
Mobilization Trigger
Trigger: Low glucose levels stimulate glucagon release.
Glucagon Action: Binds to adipocyte receptor, activates adenylyl cyclase, and increases cAMP.
PKA Activation: cAMP activates PKA, initiating phosphorylation of lipase and perilipin for triacylglycerol breakdown.
Fatty Acid Activation
Process: Fatty acid activation involves converting fatty acids into fatty-acyl-CoA.
Location: Takes place outside the mitochondria.
Purpose: Preparation for fatty acid degradation to generate energy.
Enzymatic Process
Enzyme: Catalyzed by fatty acyl–CoA synthetase.
Steps: Conjugation of fatty acid with CoA.
Energy Cost: Requires one ATP, yielding AMP and pyrophosphate.
Delta G: Reaction has a positive delta G, overcome by immediate hydrolysis of pyrophosphate.
High Energy CoA Molecules
Product: Formation of high-energy CoA molecules.
Hydrolysis: Immediate hydrolysis of pyrophosphate is crucial.
Net Delta G: Achieves a net negative delta G for the reaction.
Purpose: Provides energy for the subsequent steps in fatty acid metabolism.
Conversion Steps
Catalyst: Fatty acyl–CoA synthetase and inorganic pyrophosphatase catalyze the conversion.
Exergonic Reaction: The overall process is highly exergonic.
Preparation: Converts free fatty acids into activated fatty-acyl-CoA for efficient degradation.
Carnitine Shuttle System
Function: Transports long-chain acyl CoA through mitochondrial membranes.
Conversion: Acyl CoA is converted to acyl carnitine by carnitine acyltransferase I.
Transport: Acyl carnitine travels through the intermembrane space to the inner mitochondrial membrane.
Mitochondrial Entry
Transporter: Specific transporter facilitates the entry of acyl carnitine into the mitochondrial matrix.
Enzyme: Carnitine acyltransferase II converts acyl carnitine back to acyl CoA inside the mitochondria.
Utilization: Acyl CoA is utilized for beta-oxidation, a process in fatty acid metabolism.
Fatty Acid Entry
Process: Fatty acid entry into mitochondria via the acyl-carnitine/carnitine transporter.
Diffusion: Acyl-carnitine moves through the transporter in the inner mitochondrial membrane.
Matrix Reaction: Acyl group is transferred to mitochondrial coenzyme A in the matrix.
Inhibition Mechanism
Inhibition: Acyltransferase I is inhibited by malonyl-CoA.
Prevention: Inhibition prevents simultaneous synthesis and degradation of fatty acids.
Regulation: Malonyl-CoA regulates the balance between fatty acid synthesis and degradation.
Beta-Oxidation Overview
Stage 1: Fatty acid oxidation to acetyl-CoA.
Stage 2: Acetyl-CoA oxidation to CO2 via the citric acid cycle.
Stage 3: Electrons from Stages 1 and 2 drive ATP synthesis in oxidative phosphorylation.
Beta-Oxidation Pathway
Steps: Four-step sequence - Oxidation, Hydration, Oxidation, and Cleavage.
Acetyl-CoA Formation: One acetyl residue is removed as acetyl-CoA from the carboxyl end.
Repetition: Six more passes yield 7 additional acetyl-CoA molecules.
Acetyl-CoA Generation
Total Acetyl-CoA: Eight molecules of acetyl-CoA are formed.
Sequence: Acetyl residues removed from the fatty acyl chain in successive passes.
Carbon Source: The 7th acetyl-CoA arises from the last two carbon atoms of the 16-carbon chain.