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
Diet
TG absorbed in intestines → chylomicrons → FA absorbed in bloodstream
Adipose tissue
Glucagon signals the release of FA from adipose tissue to the bloodstream
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.