Biochemistry of Lipids and Lipoproteins

Course Information

• Course Name: BMS 131
• Lecture Number: 10
• Course Title: Lipid Chemistry 2
• Instructor: Dr Wael Elayat
• University: GALALA UNIVERSITY
• Program: Medicine and Surgery Program
• Year: Fall 2024

Intended Learning Outcomes (ILOs)

• Students will identify the significance of phospholipids.
• Students will define cholesterol and its importance.
• Students will define lipoproteins.
• Students will list different types of lipoproteins and their functions.
• Students will explain the relationship between different types of lipoproteins and atherosclerosis.

Functions of Phospholipids

• Structural component of membranes
• Aid in lipoprotein structure, facilitating lipid transport from the liver to the body; defects can lead to fatty liver.
• Solubilize cholesterol in bile; defects can lead to cholesterol stones.
• Special functions
  • DiPalmitoyl Phosphatidylcholine (DPPC): Lung surfactant
  • Cephalins: mixture of phosphatidyl serine and phosphatidyl ethanolamine, found in liver and brain, vital in blood clotting and clot lysis. Defects in these systems can cause recurrent thrombosis and recurrent fetal loss (antiphospholipid syndrome).

Special Function of Phospholipids

• DiPalmitoyl Phosphatidylcholine (DPPC) is a key component of lung surfactant.
• Dipalmityl lecithin is important lung surfactant.
• Cephalins are important in blood coagulation.

Derived Lipids

• Produced by the hydrolysis of simple or conjugated lipids, or associated with lipids by nature.
• Examples:
  • Alcohols
  • Fatty acids
  • Steroids
  • Glycerol (in triacylglycerol – TAG)
  • Phosphoglycerides
  • Vitamin A and D

Steroids

• Compounds with a steroid nucleus
• Steroid nucleus is composed of 4 rings (A, B, C, D) and 19 carbons.

Cholesterol

• Major steroid in animal tissue
• Biological importance through its role in bile acids, vitamin D, and steroid hormones.

Cholesterol-Biological Important Components

• Cholesterol is a key precursor for bile acids.
• Cholesterol is crucial for vitamin D synthesis.
• Cholesterol is a fundamental component in the production of steroid hormones.

i-Cholesterol Structure

• A steroid nucleus with an 8-carbon side chain at C-17.
• A double bond between C5 and C6.
• A hydroxyl group (OH) at C3.
• Amphipathic (having both hydrophilic and hydrophobic properties)

Cholesterol Ester

• Formed by esterifying cholesterol with unsaturated fatty acids.
• Storage form of cholesterol within cells.
• Blood cholesterol is present as either free cholesterol or cholesterol ester.

Lipoproteins

• Transport structure for insoluble lipids in the bloodstream.
• Structure: Hydrophobic core of triacylglycerols (TAGs) and cholesterol esters, with a hydrophilic outer layer of phospholipids, free cholesterol, and proteins.

Classification of Plasma Lipoproteins

• Four major types: chylomicrons, VLDL, LDL, and HDL, distinguished by size and density, determined via ultracentrifugation and electrophoresis.

Chylomicrons

• Assembled in intestinal mucosal cells and secreted into the lymphatic system.
• Transport dietary triacylglycerols and cholesterol to tissues.
• The protein component includes apo B48.
• Important for post-alimentary lipemia.

VLDL

• Major carriers of endogenous triacylglycerols,produced by liver cells.

• Acquire apo C and apo E from circulating HDL.

• Converted to IDL or VLDL remnant.

IDL

• Fate:
  • Converted to LDL.
  • Directly taken up by the liver.

LDL

• Formed from VLDL, small particles, rich in cholesterol
• Transport cholesterol from liver to peripheral tissues.
• High blood LDL levels are linked to heart disease.

LDL Receptor

• Located in coated pits in the cell membrane.
• Vital for cholesterol uptake.

HDL

• Transports cholesterol from peripheral tissues to the liver (reverse cholesterol transport).
• Inverse relationship between HDL levels and incidence of myocardial infarction.
• Secreted from the liver as discoidal nascent particles with relatively little cholesterol, phospholipids, and apoproteins (A, C, & E).

Metabolism

• Sum of biochemical reactions in cells, tissues, and the entire organism.
• Composed of interconnected pathways.
• Different pathways often intersect to form the integrated network in the Metabolic map.

Metabolic Pathways: Types

• Catabolic Pathways:
• Break down complex molecules into smaller ones, releasing energy.
• Energy-producing (exergonic)
• Usually oxidative reactions requiring hydrogen carriers (e.g., NAD+, FAD).
• Convergent process: many different molecules are broken down into a few common end products (e.g., Acetyl CoA).
• Anabolic pathways
• Build complex molecules from smaller ones, and requires energy.
• Energy-consuming (endergonic)
• Usually reductive reactions using electron donors (e.g., NADPH).
• Divergent process: Few starting precursors form a wide variety of complex products.
• Amphibolic pathways:
• Have dual function (both anabolic and catabolic).
• TCA (tricarboxylic acid) cycle is most important example.

Metabolic Pathway Regulation

• Regulation via:
  • Enzymatic activity: - Alter enzyme quantity (long-term) through gene induction or repression under hormonal control
    - Alter enzyme activity (short-term) through allosteric regulation, covalent modification.
  • Compartmentation: Isolation of different steps in metabolism within different cellular compartments like the cytosol and mitochondrial matrix.
  • Energy state and substrate availability.

Signal Transduction

• Process by which extracellular signals converted into intracellular changes
• Crucial process for communication between cells.
• Primarily involves receptor activation, second messenger production (e.g., cAMP), and target protein activation.
• Signals include: hormones, neurotransmitters, growth factors, etc.

Adenylate Cyclase Signaling by Glucagon

• Glucagon is the primary signal.
• Adenylyl Cyclase is the enzyme.
• cAMP is the second messenger.
• PKA (protein kinase A) is activated by cAMP.

Termination of Signal

• Removal of the signal: Deactivation via various mechanisms, for example,
  • Dephosphorylation of proteins via phosphatases.
  • Degradation of PKA.
  • Conversion of cAMP into AMP

Membrane related disorders: Cystic fibrosis

• Hereditary disorder.
• Affected chloride channels in the epithelial cells of the GIT and respiratory tracts
• Result in thick mucus that can obstruct the GIT and respiratory tract, and also increase bacterial infection risk.

Cell Membrane (Biological)

• Membranes are essential for cell function, providing borders and gates.
• Highly selective and semi-permeable.
• Membranes allow information transfer with receptors and specialized channels. Crucial function in cell communication and transport.

Cell Membrane Composition

• Composed of:
  • Lipids
    • Phospholipid bilayer
    • Glycolipid
    • Cholesterol
  • Proteins
    • Peripheral proteins
    • Integral proteins
  • Carbohydrates
    • Oligosaccharides covalently attached to proteins and lipids.

Chemical Composition of Membrane Lipids

• Phospholipids: major component; amphipathic molecules with hydrophobic tails and hydrophilic heads. Specialized to form the cell membrane's bilayer. Includes lecithin, cephalins, phosphatidyl inositol, etc.
• Cholesterol: amphipathic, regulates membrane fluidity.
• Glycolipids: exterior surface of cell membrane, role in cell proliferation and cell recognition. Types include sphingolipids.

Membrane Proteins

• Peripheral: located at surface; easily removed
• Integral: embedded in the membrane; require detergents or organic solvents for removal

Membrane Carbohydrates

• Found externally on the cell membrane (exclusively external)
• Typically are covalently attached to protein (glycoprotein) or lipid( glycolipids)
• Play a significant role in cell-cell recognition, communication, proliferation
• Important in disease states like cancer cell proliferation control as it influences their ability to proliferate.
• Part of blood type system (ABO)