Fatty Acids Metabolism

Page 3: Fatty Acid Metabolism Overview

• Significance: Primary energy source for the body.

• Advantages:

  • More compact storage than glycogen.

  • Specialized storage in dedicated cells.

  • Unlimited capacity for storage.

• Processes:

  • Fatty acid degradation occurs in mitochondria.

  • Ketone bodies produced serve as alternative energy source to glucose, sparing muscle protein for gluconeogenesis.

Page 4: Definition of Fatty Acids

• Structure: Long-chain hydrocarbons with carboxylic acid tails.

• Variability: Chain lengths range from 3 to 24 carbons.

• Properties: Amphipathic; contains a polar end (carboxylic acid) and a hydrophobic tail.

Page 5: Fatty Acids Naming Systems

• Structure Examples:

  • Common names and systematic names provided for various lengths and double bond configurations.

• Shorthand Notation: Presented for easy reference of fatty acids.

How FA/TG can enter the bloodstream

1. Diet

   • TG absorbed in intestines → chylomicrons → FA absorbed in bloodstream

2. Adipose tissue

   • Glucagon signals the release of FA from adipose tissue to the bloodstream

3. Liver

   • Excess glucose in the liver (not being used for ATP synthesis or glycogen synthesis) is converted into FA → TG → VLDL (very low density lipoprotein) to be used or stored in adipose tissue

Page 6: Biological Functions of Fatty Acids

• Energy Storage: Triacylglycerol form.

• Membrane Structure: Integral to cellular architecture.

• Second Messengers: Prostaglandins and thromboxanes derived from fatty acids; some are essential in diet.

Page 7: Triacylglycerol Structure

• Composition: Glycerol molecule esterified to three fatty acids.

• Energy Storage: The principal fat energy storage form in adipocytes.

Page 8: Phospholipid Structures

• Structures Overview: Various structures of phospholipids, including phosphatidic acid and phosphatidylcholine.

• Head Groups: Diverse molecules that interact with phosphate groups present.

Page 9: Membrane Structures

• Phospholipid Arrangement: Carboxylic acid end faces water; hydrophobic tails exclude water, creating bilayer and micelle structures, essential for cellular function.

Page 10: Release of Fatty Acids

• Triggers: Release involves glucagon and epinephrine, leading to cAMP rise.

• Enzymatic Action: Requires actions from ATGL, HSL, and monoglyceride lipase.

Page 11: Triglyceride Degradation Process

• Enzyme Interactions: Detailed steps of triglyceride breakdown with the roles of ATGL, HSL, and MGL highlighted.

• Transport Mechanism: Free fatty acids travel bound to serum albumin; shorter fatty acids require no binding.

Page 12: Fate of Glycerol

• Glycerol Conversion: Glycerol metabolized to glycerol-3-phosphate via glycerol kinase, which is liver-specific.

Page 13: Fatty Acid Oxidation

• Process Description: Fatty acids oxidized in two-carbon segments through beta-oxidation.

• Feeding Studies: Findings from studies lead to the identification of oxidation patterns.

Page 14: Feeding Experiments Results

• Implications: Differentiation in urine outcomes for even vs. odd-numbered carbon chain fatty acids indicates breakdown patterns in beta-oxidation.

Page 15: Beta-oxidation Mechanism

• Reaction Breakdown: Conversion of fatty acids through a series of oxidations and bond cleavages producing acetyl-CoA.

Page 16: TCA Cycle Reactions

• Comparison: Similarities between fatty acid oxidation and TCA cycle reactions, highlighting parallels in metabolic pathways.

Page 17: Fatty Acid Oxidation Steps

• Reactions Flow: Detailed mechanism showcasing the transformation of acyl-CoA through different oxidation stages.

Page 18: Big Picture of Fatty Acid Oxidation

• Overall Process: Activation, transport, oxidation process culminating in acetyl-CoA production within mitochondria.

Page 19: Fatty Acid Activation

• Activation Process: Description of how fatty acids are activated via fatty acyl-CoA synthetase, requiring ATP as part of the process.

Page 20: Overview of Fatty Acid Oxidation Process

• Step-by-Step: Summary of key enzymes and processes involved in mitochondrial fatty acid oxidation.

Page 21: Transport into Mitochondria

• Mechanism: Details of carnitine's role and associated enzymes in transporting fatty acids.

• Regulation: Malonyl-CoA's inhibitory role on CPT-I discussed.

Page 22: Malonyl-CoA Overview

• Production and Regulation: Formation and regulation effects on fatty acid oxidation and synthesis pathways.

Page 23: Oxidation of Saturated Fatty Acids

• Enzyme Functions: Detailed information on specific enzymes involved in the oxidation of saturated fatty acids.

Page 24: Acyl-CoA Dehydrogenase Isoforms

• Variety of Isoforms: Specific enzymes designated for different chain-length fatty acids (Short, Medium, Very Long Chain).

Page 25: Peroxisomal Fatty Acid Oxidation

• Mechanism and Steps: Description of how very long-chain and branched fatty acids are oxidized using acyl-CoA oxidase forms.

Page 26: Energy Yield

• Calculation: Breakdown of ATP yield from oxidation of C18:0 to carbon dioxide and water following fatty acid degradation process.

Page 27: Oxidation of Unsaturated Fatty Acids

• Mechanism Differences: Variations in the oxidation pathways of unsaturated fatty acids compared to saturated ones.

Page 28: Unsaturated Fatty Acids Continued

• Further Pathways: Enzymatic actions required to navigate challenges of double bonds in unsaturated fatty acids.

Page 29: Continued Oxidation of Unsaturated Fatty Acids

• Finalize Pathways: Steps leading to successful oxidation after addressing double bond conditions.

Page 30: Final Steps in Unsaturated Fatty Acid Oxidation

• Oxidative Progression: Final processes leading to the generation of acetyl-CoA from unsaturated fatty acids.

Page 31: Isomerization Effects

• Isomerization Impact: Role of isomerization in facilitating continued oxidation of unsaturated fatty acids.

Page 32: ATP Yield from Unsaturated Fatty Acids

• Differences in Yield: Comparison of ATP yield based on double bond positions between saturated and unsaturated fatty acids.

Page 33: Odd-Chain Fatty Acid Metabolism

• Pathway Specifics: Process for handling propionyl-CoA during the final degradation round of odd-chain fatty acids highlighted.

Page 34: ATP Yield from Odd-Chain Fatty Acids

• Yield Considerations: Detailed breakdown of ATP yield accounting for conversions of propionyl-CoA and subsequent metabolic processes.

Page 35: Other Oxidation Pathways

• Notable Processes: Various oxidation mechanisms (alpha-, omega-, and peroxisomal) relevant to specific branched-chain fatty acids.

Page 36: Introducing FADH2 to ETC

• Electron Transfer Mechanism: Explanation of how FADH2 from fatty acid degradation interacts with the electron transport chain.

Page 37: Ketone Bodies Overview

• Function: Importance during glucose deprivation as an alternative fuel source.

Page 38: Ketone Body Biosynthesis

• Structural Steps: Overview of the enzymatic processes contributing to the synthesis of various ketone bodies.

Page 39: Ketone Body Metabolism

• Fate of Acetone and Others: Acetone’s fate outlined; significant metabolic transformations of hydroxybutyrate and acetoacetate stated.

Page 40: Regulation of Ketone Body Synthesis

• Mechanisms: Steps detailing how fatty acid levels and energy status influence ketone body production.

Page 41: Fatty Acid and Ketone Body Utilization Timing

• Graphical Depiction: Changes in free fatty acids, glucose, and ketone concentrations during fasting stages.

Page 42: Metabolic Defects Overview

• Defects in Oxidation: Connection of various genetic mutations to specific metabolic disorders like glutaric acidemia and the consequences on fatty acid oxidation.

Page 43: Fatty Acid Transport Issues

• Indicators: Information on specific deficiencies (e.g., carnitine) leading to energy and transport problems in fatty acid metabolism.

Page 44: MCAD Deficiency Case Study

• MCAD: Frequency, genetic background, hypoglycemia triggers, and metabolic consequences explained.

Page 45: Peroxisomal Defects

• Disease Overview: Brief exploration of disorders related to peroxisomes, including Zellweger syndrome, Refsum disease, highlighted challenges related to fatty acid oxidation.

Page 46: Jamaican Vomiting Disease

• Etiology and Effects: The role of hypoglycin and resultant metabolic disturbances detailed.

Page 47: Regulation Mechanisms

• Long-Term Adaptations: Overview of enzyme regulation in response to caloric intake detailing up-regulation and down-regulation.

Page 48: Hormonal Regulation Overview

• Regulatory Events: Insulin's role in promoting or inhibiting specific pathways within fatty acid metabolism.

Page 49: Allosteric Regulation Insights

• Impact of Regulators: How ketone bodies impact hormone-sensitive lipase activity in regulation of fatty acid synthesis and oxidation.

Page 50: Glucagon Effects

• Mechanistic Understanding: Steps detailing glucagon's role in activating fatty acid mobilization and gluconeogenesis.

Page 51: Case Study (Same as Page 2)

• Reiteration of Case Study: Revisits the two-month-old child and highlights signs and conditions noted.

Page 52: Discussion Questions

• Review Questions: Set of questions posed for students, focusing on metabolic processes during exercise and identifying enzyme defects based on observed conditions in infant patients.