Lipids Lecture Notes PDF

Lipids Dr Charlotte Lawson School of Pharmacy and Biomedical Sciences [email protected] Where opportunity creates success Learning Outcomes Explain how lipids are classified Understand lipid structure and nomenclature Outline how lipids are transported Appreciate the different functio...

Lipids Dr Charlotte Lawson School of Pharmacy and Biomedical Sciences [email protected] Where opportunity creates success Learning Outcomes Explain how lipids are classified Understand lipid structure and nomenclature Outline how lipids are transported Appreciate the different functions of lipids in the body Questions? Please use the TEAM! No such thing as a stupid question! If you wondered, then so did someone else! I will post emailed questions on the Team so please save us both a job! If you know the answer to the question, please feel free to post – we are all in this together! Biomolecules Organic molecules that are formed by living organisms – Consists majorly of Carbon, Hydrogen, Oxygen and Nitrogen Four major classes Lipids Proteins Carbohydrates Nucleic acids Role of Biomolecules Energy (carbohydrates, lipids, proteins) Building materials (carbohydrates, lipids, proteins) Genetic Information (nucleotides) Communication (proteins, lipids) Drug Targets  Lipids a group of water-insoluble organic molecules that can be extracted from tissues by nonpolar solvents. They are not polymers. Oxidation of lipids releases large amount of energy. Main biological functions include: - Energy storage - Heat/insulation - Structural components of cell membranes - communication Types of lipids Fatty acids Triacylglycerols Phospholipids Sphingolipids Steroids Fatty acids Fatty acids exist either free or as esters (TAG). FAs are found at high levels in plasma during fasting. Circulate bound to albumin Fatty acids Long hydrocarbon chains with of varying length (H(CH2)nCOOH) Amphipathic nature. – Chain length varies from 4-40 carbons (short, medium and long) – C16 and C18 forms most common in plants and animals. Fatty Acids Carboxyl head group – Polar – Hydrophilic Fatty acid chain – Hydrophobic. Saturated or unsaturated fatty acids Fatty acid saturation Usually contain an even number of carbon atoms Saturated – Single bonds between carbons – Linear appearance – Solid at room temp Unsaturated – One or more C=C bonds – C=C double bond gives distinct bend – Reduces Tm – liquid at room temp Diversity of characteristics Fatty acids Double bonds prevent tight packing Fatty acids FA’s rarely occur free in nature. Often combined with Glycerol to form Triacylglycerols (TAGs). Condensation Reaction Ester bond Triacylglycerols (TAG) Also known as Triglycerides Glycerol head group attached to 3 fatty acid chains Stored as cytoplasmic ‘lipid droplets’ Main storage for energy – Long term storage and insulation – High in energy Triacylglycerols (TAG) 90% of dietary intake of lipids is in the form of TAG. Liver also makes TAG, which is transferred to tissues in lipoproteins. TAG is hydrolysed to free fatty acids FFA and glycerol by enzyme (Lipase). Triacylglycerols Triacylglycerols TAGs are fats Fatty acid can be the same (homogenic) or different (heterogenic). Fats Fats with saturated fatty acids are saturated fats. – Most animal fats are saturated. – Solid at room temperature. Fats with unsaturated fatty acids are unsaturated fats. – Plant and fish fats, known as oils, are liquid at room temperature. – Double bonds cause chain kinks. Fats- Function Energy storage – Stores more than twice the energy as polysaccharides (e.g. starch or glycogen) In mammals – Fats stored in adipose tissues – Cushion vital organs – insulation Phospholipids Major component of cell membranes Can form lipid bilayers Two forms of complex lipids: – Phosphoglyceride – Sphingolipid http://en.wikipedia.org/wiki/ File:Phospholipids_aqueous_solution_structures.svg Phospholipids Major component of cell membrane Glycerol + 2 FA’s + Phosphate group (Phosphatidic acid) Glycerophospholi pids Phospholipids FA’s are 14-24C. When R is choline: Glycerophosphatidyl choline. Membrane Lipids – Phospholipids  Extra slide! glycosylphosphatidylinositols (GPIs) Glycolipids attached to proteins as membrane anchors Alternative membrane anchors for trans- membrane proteins Role in cell signalling Enzymes Adhesion molecules Complement regulatory proteins  Sphingolipids Based on sphingosine (C18 amine alcohol) instead of glycerol FA’s and R groups added Functions include: o Cell recognition- carbohydrate o Signalling o Lipid rafts o Glycosphingolipids are the major glycolipids in humans Sphingolipids Sphingomyelin Glycosphingolipid s Cholesterol The principal steroid synthesized by mammals Synthesized in the liver with variable amounts obtained from the diet. Component of eukaryotic cell membranes Precursor from which all other steroids are synthesized. Cholesterol Synthesis Average total body cholesterol = 150g of which 90% as part of cell membrane structure Rate-limiting step on the pathway for synthesis of cholesterol, HMG CoA Reductase, is a major control point  Steroids Steroids are lipids with a common carbon skeleton consisting of four fused carbon rings. Different steroids are created by Cholesterol varying functional groups attached to the rings. Steroids Cholesterol is the base for all steroid hormones – Glucocorticoids – Mineralocorticoids – Androgens – Oestrogens Cholesterol – Progestogens Also the base for bile acids Steroid hormones Cholesterol Estradiol (E2) Progesterone Testosterone (Wikipedia) How are lipids digested and transported? Most lipids are ingested as triglycerides – water insoluble – difficult to digest Solution – Bile Lipid Transport Dietary lipids are transported from the intestine to liver (exogenous) Lipids then transported from liver to peripheral tissues (endogenous) This transport is undertaken by apolipoproteins – Large mostly spherical complexes – Core of triglycerides and cholesterol esters – Surface of phospholipids and some cholesterol – CM, VLDL, LDL, HDL Lipoproteins - classes Chylomicron – Lowest density (low protein:lipid ratio) – Highest % weight triacylglycerols VLDL – 2nd highest in triacylglycerols as % of weight LDL – Highest in cholesterol esters as % of weight HDL – Highest in density due to high protein:lipid ratio wikipedia Relative amounts of lipids and proteins in different classes of lipoproteins Summary Lipids are a class of hydrophobic organic compounds FA’s are long chain carboxylic acids FA’s may be saturated or unsaturated TAG’s are 3 FA’s esterized to glycerol PL’s are TAG’s, but have a phosphate group in place of one FA Sphingolipids use a sphingosine backbone and may have functional R group. Cholesterol is the major steroid synthesized in mammals. Dietary lipids are metabolised and carried as lipoproteins Further reading Moran, Laurence A (2014) Principles of Biochemistry, Fifth edition. Chapter 9: Lipids and membranes ISBN: 9781292034966 (e-book) Rodwell, Victor W ; Bender, David A ; Botham, Kathleen M ; Kennelly, Peter J ; Weil, P. Anthony (2018) Harper’s Illustrated Biochemistry 31st edition. Chapter 21. Lipids of Physiological significance. ISBN: 9781259837937 Questions? Please use the TEAM! No such thing as a stupid question! If you wondered, then so did someone else! I will post emailed questions on the Team so please save us both a job! If you know the answer to the question, please feel free to post – we are all in this together!