Lipid Metabolism Study Notes

Introduction to Lipid Metabolism

  • Dr. Mark Leyland from the University of Leicester

  • Focuses on various aspects of lipid metabolism pertinently affecting the human body.

Key Aspects of Lipid Metabolism

  • Transport of lipids

  • Processing of dietary lipids

  • Regulation of fatty acid oxidation and synthesis

  • Mobilization of lipid stores

  • Metabolism of ketone bodies

  • Regulation of cholesterol metabolism

  • Regulatory aspects of lipid metabolism

Understanding Lipids

  • Definition: Lipids are a group of structurally diverse substances that are generally insoluble in water, categorized largely into hydrophobic molecules.

    • Chemical Composition: Most lipids primarily consist of Carbon (C), Hydrogen (H), and Oxygen (O).

    • Phospholipids contain Phosphorus (P) and Nitrogen (N).

    • Energy Storage: Lipids are more reduced than carbohydrates, thus releasing more energy when oxidized during metabolic processes.

Classes of Lipids

  • Visual representation of lipid structures, delineating various lipid classes.

Ketone Bodies

  • Metabolic Role: Ketone bodies serve as water-soluble fuel molecules that the body can utilize when glucose levels are low.

  • Key types include:

    • D-3-Hydroxybutyrate

    • Acetoacetate

    • Acetone

  • Production primarily associated with the breakdown of fatty acids.

Source of Body Lipids

  • Lipids available for body utilization come from:

    • Diet (sources from food)

    • Synthesis (endogenous production)

    • Storage (lipids stored within the body)

  • Lipid utilization necessitates transportation throughout the body.

Transport of Lipids

  • Mechanism of Transport: Lipids are transported via spherical lipoprotein particles.

    • Composition of Lipoproteins: Comprise a neutral core filled with triacylglycerols (TAGs) and cholesteryl esters (CEs), with an outer shell made of phospholipids, free cholesterol, and apolipoproteins.

Properties of Lipoproteins

  • Naming: Lipoproteins are classified based on sedimentation position in centrifugation.

  • Characteristics: (Table 26.1)

    • Composition varies across lipoproteins, influencing specific physiological roles:

    • Chylomicrons:

    • Density: <0.95 g/ml

    • Diameter: 75 - 1200 nm

    • Main Role: Dietary fat transport (86% TAG, 3% CE, 1% C, 8% PL)

    • Apolipoproteins: B48, C, E

    • Endogenous fat transport lipoprotein:

    • Density: 0.95 - 1.006 g/ml

    • Diameter: 30 - 80 nm

    • Low-Density Lipoprotein (LDL):

    • Density: 1.019 - 1.063 g/ml

    • Diameter: 18 - 25 nm

    • Main Role: Cholesterol transport (10% TAG, 38% CE)

    • Apolipoprotein: B100

    • High-Density Lipoprotein (HDL):

    • Density: 1.063 - 1.21 g/ml

    • Diameter: 7.5 - 20 nm

    • Main Role: Reverse cholesterol transport

    • Apolipoproteins: A

  • Abbreviations: TAG - triacylglycerol, CE - cholesteryl ester, C - free cholesterol, PL - phospholipid.

Cholesterol Uptake Mechanism

  1. Receptor-Mediated Endocytosis:

    • Step 1: The LDL receptor synthesizes in the rough endoplasmic reticulum, moves to plasma membrane via Golgi apparatus.

    • Step 2: LDL receptor binds to apoB-100 on LDL, triggering endocytosis.

    • Step 3: LDL is internalized into endosomes.

    • Step 4: The LDL receptor is segregated into vesicles and recycled back to the surface.

    • Step 5: The endosome fuses with lysosome.

    • Step 6: Lytic enzymes within the lysosome decompose apoB-100 and cholesteryl esters, yielding amino acids, fatty acids, and cholesterol.

Chylomicron Functionality

  • Chylomicrons Characteristics:

    • Lipid Composition: Mainly TAG.

    • Protein Composition: ApoB-48, apoCII, apoE.

    • Functionality: Transport dietary lipids to tissues.

    • Activation: ApoCII activates lipoprotein lipase (LPL) located on the lumenal wall of tissues for TAG hydrolysis.

    • Chylomicron Remnants: Created post hydrolysis and removal of apoB-48/apoCII.

Processing of Dietary Lipids

  1. Solubilization: Lipids interact with bile salts to become solubilized.

  2. Breakdown: Lipases degrade solubilized lipids into constituent fatty acids (FAs) and monoacylglycerols (MAGs).

  3. Packaging & Transport: TAGs are re-formed in mucosal cells for transport.

  4. Release and Uptake: Cargoes are released and taken up by target tissues.

Regulation of Lipid Digestion

  • Regulatory Hormones:

    • Cholecystokinin (CCK): Slows gastric contents release; stimulates bile release.

    • Secretin: Stimulates pancreatic secretion in reaction to lipids and amino acids in the small intestine.

Chylomicron Assembly & Transport

  • Chylomicron Formation: Begins in the endoplasmic reticulum (ER) of intestinal epithelial cells, incorporating apoE and apoCII from HDL, leading to mature chylomicrons.

  • Uptake by Tissues:

    • Lipoprotein Lipase Role:

    • An extracellular enzyme adhering to endothelial cells, hydrolyzing TAG into glycerol and free fatty acids (FFA).

    • ApoCII is a cofactor essential for this mechanism.

  • Overall Utilization of Lipids by Tissues: FFA serves as fuel for muscle cells or is re-esterified in adipose tissues, while glycerol is converted to glycerol-3-phosphate in the liver.