Lipids and Lipoproteins Presentation PDF

Lipids and Lipoproteins Nnadi Emmanuel Ebuka University of Hertfordshire University of October 2024 Hertfordshire Lipid...

Lipids and Lipoproteins Nnadi Emmanuel Ebuka University of Hertfordshire University of October 2024 Hertfordshire Lipids and Lipoproteins 1  Learning Objectives What are Lipids? Plasma Lipids Lipid Physiology Lipid Disorders Lipids and NICE 2  Introduction Lipids are a group of chemically diverse compounds characterized by high hydrophobicity (low solubility in water) Soluble in organic solvents such as acetone, chloroform, amongst others. They have significant biological roles Fats, oils, and waxes are lipids 3  Biological Roles of Lipids Energy storage Structural role as components of plasmatic membranes Enzyme cofactors Hormones Membrane anchors for proteins Signaling messengers Electron carriers Emulsifier agents (digestion and blood transport Solvents for vitamins A, D, E, & K. 4  Classification of Lipids (Bloor’s) I. Simple Lipids a. Natural fats (Triglyceride) b. Waxes True waxes Cholesterol esters (fatty acid + cholesterol) Vit A and Vit D esters II. Compound lipids a. Phospholipids b. Glycolipids c. Sulpholipids d. Aminolipids (Proteolipids) e. Lipoprotein Chatterjea & Shinde, (2011).  Classification of Lipids cont. III. Derived Lipids: product of Groups I & II hydrolysis a. Fatty acids b. Mono- and Diglycerides c. Alcohols Straight chain alcohols, water insoluble, obtained from hydrolysis of wax Cholesterol and steroids (including Vit. D). Glycerol Some carotenoids IV. Miscellaneous Vitamins E and K Carotenoids Squalene Chatterjea & Shinde, (2011).  Classification of plasma lipids Four forms of lipid present in plasma Fatty Acids Triglycerides Phospholipids Cholesterol 7  Fatty Acids Highly reduced linear hydrocarbon chains of various lengths with a carboxylic group at the end CH3(CH2)nCOO- (n= 4 to 36 C) Fatty acids can be: Saturated Unsaturated 8  Saturated Fatty Acids   OH  O Lauric acid (C12, 12:0, n-dodecanoic acid) Contain only single bonds in the hydrocarbon chain are “saturated” with hydrogens and are very linear, e.g. animal fats Even-numbered fatty acids predominate Palmitic (16 carbons) and stearic (18 carbons) are the most common 9  Unsaturated Fatty Acids OH O Palmitoleic acid (16:19, 9-hexadecanoic acid) Monounsaturated (one double bond ) Polyunsaturated (more than one double bond). In nature are more common than saturated fatty acids Considered healthier than saturated fats 10  Triglycerides Esters between glycerol and 3 fatty acids The most abundant family of lipids in plant and animal cells, Major components of human diet Function Energy storage for cells that accumulate in the form of oily droplets Storage and transport (does not require carrying large amounts of water) Used for insulation Water insulation (hydrophobic) Thermal insulation (low conductivity) 11  Phospholipids Complex lipids, resembling Triglycerides BUT containing a phosphate and nitrogenous base. Functions: Energy storage for cells Surfactants (Sphingomyelin) Water insulation (hydrophobic) Storage and transport (does not require carrying large amounts of water) Used for insulation Thermal insulation (low conductivity) 12  Cholesterol Cholesterol composition is that of a perhydrocyclopentanthroline ring structure. 13  Cholesterol contd/… Synthesis involves 25 separate enzyme steps beginning with Acetyl Co A 14  Cholesterol contd/… The most abundant steroid in the body. Occurrence: Most of the cholesterol in the blood is present as esters, Most of the cholesterol in cells and tissues is the free form. Functions: Structural component of cell membranes Precursor for other steroids such as steroid hormones and bile salts Protective agent for skin (up to 300 mg per day secreted) Sources Natural biosynthesis Dietary 15  Lipoproteins Provide a water-soluble means to transport hydrophobic lipids Consist of a core of insoluble non-polar cholesterol esters and Triglycerides surrounded by proteins, phospholipids, and Free Cholesterol with their polar groups facing outwards. Synthesised in the liver or intestine. After secretion they are modified by enzymes and their remnants taken up by receptors on the cell surface. Regulated by the protein component of the complex, the Apolipoproteins. 16  Plasma Lipids and Lipoproteins Lipids are ‘plasma water’ insoluble Transported by lipoproteins in the bloodstream Types of Lipoproteins: Chylomicrons, Very Low Density Lipoproteins (VLDL), Low-density lipoprotein (LDL), and High Density Lipoproteins (HDL) 17  Chylomicrons 75 – 120 nm 81.3% Triglycerides 9.1% Cholesterol and Cholesterol esters 7.1% Phospholipids 2.5% Protein Contain Apolipoproteins A & B Apolipoproteins C & E are acquired post secretion Source – Intestine Function – Transport exogenous lipid from the intestine to all cells Lifespan – From formation after a meal until the remnant have been removed by the liver takes approximately 6 hrs. 18  VLDL 25-75 nm 51.8% Triglycerides 22.2% Cholesterol and Cholesterol esters 26.0% Phospholipids 7.1% Protein Contain Apolipoproteins B, C & E Source – Synthesised in the Liver Function Transport of endogenous triglyceride. Lifespan – Varies as the core shrinks due to loss of Triglycerides, they shrink to become LDL Supply of nutrients between meals. 19  ~ 22 nm LDL 9.3% Triglycerides 50.0% Cholesterol and Cholesterol esters 20.0% Phospholipids 20.7% Protein Contain Apolipoprotein B Source – Metabolism of VLDL via IDL Function Energy – Triglycerides are degraded in the cell to fatty acids and glycerol Cell replication - Apoproteins degraded to amino acids Cell Integrity – Cholesterol and cholesterol esters used to repair/maintain cellular membranes. Steroid Hormone neogenesis - Cholesterol and cholesterol esters used to produce Cortisol, testosterone, oestrogens and androgens Cellular Uptake – Governed by the number of Apo B cell receptors, abnormalities of which may lead to atherosclerosis and hyperlipidaemia. 20  HDL 7 – 10 nm 8.1% Triglycerides 20.0% Cholesterol and Cholesterol esters 21.9% Phospholipids 50% Protein Contain Apolipoproteins A, C & E Source Intestine & Liver Cellular site via action of Lecithin-Cholesterol Acyltransferase and ApoA1 on liver precursors. Function Transport of Cholesterol and Cholesterol esters to the Liver The liver produces a disc containing phospholipids, Apolipoproteins and minimal Cholesterol and Triglyceride. LCAT and Apo A1 esterifies Free cholesterol and internalises this. Once full -> Liver 21  Apolipoproteins Apolipoprotein Occurrence Known Functions A Chylomicrons Cofactor for LCAT (A-1) HDL B Chylomicrons Secretion of chylomicrons VLDL, IDL Secretion of VLDL LDL Binding of LDL to receptors C HDL, VLDL, IDL Cofactor for Lipoprotein chylomicrons lipase (C-II) (from HDL) E HDL, VLDL, IDL Binding of IDL and remnant chylomicrons particles to receptors (from HDL) 22  Lipid Physiology Exogenous - lipid constitutes a source of access to the necessary Fatty Acids as well as Triglycerides Endogenous - Phospholipids and Cholesterol They are relatively insoluble and are carried in bodily fluids as soluble protein complexes known as Lipoproteins 23 9/8/20XX 24 Lipid Disorders  Lipid Disorders Dyslipidaemia: Increased LDL + reduced HDL Hypertriglyceridaemia: Increased TG (>150mg/dl) Hypercholesterolaemia: Total Chol. >200mg/dl Increase LDL & VLDL Reduced HDL Hyperlipidaemia: Increased LDL + TG Mixed hyperlipidaemia 26  Causes of Lipid Disorders Inherited or Familial Disorders Acquired Disorders 9/8/20XX PRESENTATION TITLE 27 Fredrickson Classification of the Hyperlipidemias (inherited) Relative Plasma Plasma frequenc Phenotyp Lipoprotein(s cholester triglycerid Athero- y e ) elevated ol level e level genicity in US I Chylomicro Normal  –