Fatty Acid Metabolism
Page 1: Fatty Acid Metabolism Overview
Key Metabolites and Processes
Adipose Cells: Store fat for energy.
Glucose: Primary energy source, can produce fatty acids via glycolysis.
VLDL (Very Low-Density Lipoprotein): Transport lipids from the liver.
Acetyl-CoA: Product from glucose metabolism; key player in fatty acid synthesis.
Palmitate: A 16-carbon saturated fatty acid produced from acetyl-CoA.
Triglycerides (TG): Storage form of fatty acids, made from glycerol and fatty acids.
Lipid Metabolism Pathway
Starting Materials: Glucose transforms into glycerol-3-phosphate and fatty acids.
CoA Activation: Acetyl-CoA increases fatty acid chain lengths by 2 carbons during synthesis.
Page 2: Learning Goals
Objectives for Understanding Lipid Metabolism
Summarize the digestion and storage of lipids.
Describe the degradation of fatty acids via beta-oxidation.
Explain the role of acetyl CoA in fatty acid metabolism.
Understand ketone body production during beta-oxidation.
Describe the regulatory roles of different organs: liver, adipose tissue, muscle, brain.
Discuss the antagonistic effects of glucagon vs insulin on metabolism.
Page 3: Digestion of Lipids
Lipid Breakdown in the Body
Triglycerides: Emulsified into droplets in the intestine by bile salts.
Bile Components: Include lecithin, cholesterol, bile salts, and pigments.
Pancreatic Lipases: Hydrolyze triglycerides into monoglycerides and free fatty acids.
Absorption: Intestinal epithelial cells absorb and reassemble triglycerides.
Chylomicrons: Lipoprotein particles that transport triglycerides to adipocytes.
Page 4: Micelles
Structure of Micelles
Micelles formed from lecithin with long hydrophobic tails and hydrophilic heads.
Page 5: Bile Salt Structures
Role of Bile Salts
Synthesized in the liver, stored in the gallbladder, and released into the duodenum.
Major bile salts include cholate and chenodeoxycholate.
Page 6: Emulsification
Process of Emulsification
Fat globules are broken up and coated with lecithin and bile salts to form droplets.
Page 7: Fat Hydrolysis
Action of Pancreatic Lipase
Hydrolyzes the first and third fatty acids from triglycerides, leaving the middle one intact.
Page 8: Action of Pancreatic Lipase (Repeat)
Similar to Page 7
Reinforces the process of hydrolysis performed by pancreatic lipases on emulsification droplets.
Page 9: Micelle Formation
Composition of Micelles
Micelles serve to transport various lipids including monoglycerides, cholesterol, and fatty acids.
Page 10: Chylomicron Formation
Lipid Absorption in Intestinal Cells
Intestinal cells absorb lipids, resynthesize triglycerides, and package them into chylomicrons.
Page 11: Chylomicron Exocytosis
Mechanism of Chylomicron Release
Chylomicrons packaged into vesicles by the Golgi complex and released via exocytosis, entering the lymphatic system.
Page 12: Lipid Storage
Energy Storage and Utilization
Fatty acids are stored in adipocytes as triglycerides, which are hydrolyzed for energy when needed.
Page 13: Overview of Fatty Acid Degradation
β-Oxidation
Fatty acids are converted into 2-carbon fragments via β-oxidation, releasing acetyl-CoA.
Each cycle produces FADH2 and NADH, similar to the citric acid cycle reactions.
Page 14: Reactions of β-Oxidation
Detailed Steps
Initial activation of fatty acids produces fatty acyl-CoA.
Subsequent steps consist of oxidation, hydration, and thiolysis reactions.
Page 15: Step 1 of β-Oxidation
Enzyme Activity
Enzymes located in mitochondria activate fatty acids to fatty acyl-CoA.
Page 16: Activation Reaction
Formation of Acyl-CoA
Energy investment as ATP is used to form a high-energy thioester bond.
Page 17: Crossing Into the Matrix
Transport of Fatty Acyl Groups
Acyl groups react with carnitine to cross mitochondrial membranes; then regenerated as fatty acyl-CoA.
Page 18: β-Oxidation – Step 2
Oxidation Process
The removal of hydrogen atoms reduces FAD to FADH2 during the second step.
Page 19: β-Oxidation – Step 3
Hydration Process
Water added to double bond results in hydroxylation of the β-carbon, catalyzed by enoyl-CoA hydrase.
Page 20: β-Oxidation – Step 4
NAD Reduction
The enzyme L-β-hydroxyacyl-CoA dehydrogenase facilitates the dehydrogenation of the β-carbon, producing NADH.
Page 21: β-Oxidation – Step 5
Cleavage Reaction
The enzyme thiolase cleaves the fatty acyl-CoA, releasing acetyl CoA.
Page 22: Subsequent Acetyl Units
Final Steps of Degradation
The process continues until the entire fatty acid is degraded into acetyl-CoA.
Page 23: Complete Oxidation of Palmitic Acid
Detailed ATP Yield Calculation
Palmitic acid undergoes β-oxidation and citric acid cycle yielding approximately 129 ATP.
Page 24: Complete Oxidation of Myristic Acid
Overview of Myristic Acid
Mentioned as another saturated fatty acid undergoing similar metabolic processes.
Page 25: Ketone Bodies
Formation from Excess Acetyl-CoA
When glucose and β-oxidation occur at the same rate, high levels of acetyl-CoA can lead to ketogenesis.
Page 26: Ketosis
Conditions Leading to Increased Ketone Bodies
Occurs during starvation or low-carb diets, and can lead to ketoacidosis if unchecked.
Page 27: Acetoacetate
Formation and Utilization
Acetoacetate can produce acetone and is used as an energy source particularly by the heart.
Page 28: Fatty Acid Synthesis
Pathway of Fatty Acid Production
Excess acetyl CoA from carbs is used to synthesize fatty acids in the cytoplasm.
Page 29: Two Stages of Synthesis
Initiation & Elongation
Repetitive addition of 2-carbon units via fatty acid synthase and hydrocarbon chain growth.
Page 30: Sequential Addition of Two-Carbon Fragments
Detailed Reaction Overview
Utilization of NADPH, dehydration, and hydrolysis to synthesize palmitate from ACP.
Page 31: Synthesis of Palmitate
End Products
Main output is 16- and 18-carbon fatty acids from the synthesis pathway.
Page 32: Comparison of β-Oxidation and Fatty Acid Synthesis
Key Differences
Location, carriers, involved enzymes, and electron carriers differ between synthesis and degradation.
Page 33: Comparison Summary
Metabolism Profiles
Detailed tabulated comparison for lipid biosynthesis and degradation across different parameters.
Page 34: Regulation of Lipid Metabolism
Organ-Specific Metabolism
Dependency of fatty acid metabolism varies by organ including liver, adipose, muscle, and brain.
Page 35: Representation of Liver and Lipid Metabolism
Blood Glucose Regulation
Insulin stimulates lipid synthesis; glucagon promotes breakdown after fasting.
Page 36: After a Meal
Insulin's Role
Insulin stimulates synthesis of fatty acids and triglycerides transported to adipose tissue.
Page 37: In Starvation or Fasting
Glucagon’s Action
Fatty acids are converted to ketone bodies and sent for ATP production.
Page 38: Adipose Tissue
Function and Control
Major fat storage; triglyceride synthesis depends on lipases and glycolysis intermediates.
Page 39: Muscle Tissue
Energy Use
Resting muscle prefers fatty acids, while active muscle uses glycolysis; heart utilizes ketones.
Page 40: Effects of Insulin on Metabolism
Overview of Insulin Actions
Secreted in response to high glucose, promotes glycogen synthesis and fat storage.
Page 41: Effects of Glucagon on Metabolism
Overview of Glucagon Actions
Increased presence under low glucose conditions to stimulate fat breakdown and energy release.
Page 42: Comparison of Hormonal Effects
Metabolic Changes Induced by Insulin and Glucagon
Effects on glycogen, amino acids, and fat metabolism compared.
Page 43: Summary of Hormonal Effects
Insulin vs Glucagon
Contrasting actions of insulin and glucagon during feeding vs fasting states.