Unit 3 Lipid Chemistry PDF

CHY2026: General Biochemistry Unit 3: Lipid Chemistry  Fatty Acids ❖ General formula CnH2n+1COOH ❖ When the fatty acids are not attached to other molecules: “free” fatty acids ❖ Fatty acids are amphipathic compounds: hydrophilic carboxylic group and hydrophobic aliphatic tail ❖ Even num...

CHY2026: General Biochemistry Unit 3: Lipid Chemistry  Fatty Acids ❖ General formula CnH2n+1COOH ❖ When the fatty acids are not attached to other molecules: “free” fatty acids ❖ Fatty acids are amphipathic compounds: hydrophilic carboxylic group and hydrophobic aliphatic tail ❖ Even number straight chain fatty acids are found abundantly in plants and animals (C16 – palmitic acid; C18 stearic acid ……C10)… reflecting the pathway for their biosynthesis from the two-carbon building-block acetyl CoA ❖ Less than 1% of the total fatty acids are odd number fatty acids ❖ Bacteria, however, possess the ability to synthesize odd- and branched-chain fatty acids. As a result, ruminant animal fat contains odd-numbered fatty acids (15), due to the action of bacteria in the rumen  Saturated Fatty Acids ❖ If the hydrocarbon chain contains no double bonds then the fatty acid is saturated Unsaturated Fatty Acids ❖ Unsaturated fatty acids contain double bond(s) in the hydrocarbon chain ❖ Unsaturated fatty acids may be classified based on the degree of unsaturation Monoethanoid acids: oleic acid Diethanoid acids: linoleic acid Triethanoid acid: linolenic acid EFA (must be obtained from diet) N.B all foods contain small quantities of bound fats or invisible fats (takes care of half to the daily fat requirements Many fatty acids are unsaturated, some are polyunsaturated, e.g., those derived from linoleic acid Unsaturated Fatty Acids Linoleic Acid (once called vitamin F) Linolenic Acid  Fatty Acids ❖ Many naturally occurring fatty acids contain 2-3 double bonds in the cis position ❖ The carbon chains of saturated fatty acid tend to be fully extended because this minimizes repulsion between neighboring methylene groups ❖ The cis conformation of the double bond of an unsaturated fatty acid puts a rigid bend in the carbon chain that interferes with packing causing reduced van der Waals attractions between molecules http://courses.washington.edu/conj/membrane/fat ❖ Therefore unsaturated fatty acids have lower tyacids.htm melting points Saturated fatty acids Unsaturated fatty acids Solids at room temperature Liquid at room temperature They are found in animals They are found in plants Stored mainly in liver and bone Stored in seeds and fruits Oxidative rancidity is observed less Oxidative rancidity observed more frequently frequently Properties of Fatty Acids ❖ Fatty acids are important sources of fuel …when metabolized they yield large quantities of ATP ❖ Many cell types can use either glucose or fatty acids for fuel. In particular the heart and skeletal muscle prefer fatty acids  Fatty Acids ❖ There are enzymes present in the ER that are responsible for desaturating fatty acids (i.e. adding cis double bonds) ❖ The body is able to convert stearic acid to oleic acid by inserting a double bond but incapable of inserting further double bonds ❖ Humans have carbon 4,5,6 and 9 desaturases, but lack the ability to introduce double bonds from carbon 10 to the ω end of the chain ❖ Unsaturated fatty acids from vegetable oil can have their double bonds removed by adding hydrogen (Hydrogenation): hydrogenated fat (saturated fat even though derived from vegetable oil)  Chemical Properties Hydrogenation ❖ Unsaturated fatty acids react with gaseous hydrogen to yield saturated fatty acids ❖ Catalyst:Pt or Ni ❖ This reaction is used in the manufacture of candles, vegetable shortening and margarines ❖ During partial hydrogenation, some of the unsaturated fatty acids, which are normally found as the cis isomer about the double bonds, are changed to a trans double bond and remain unsaturated ❖ Trans fat have a more linear shape than cis fat ❖ Trans fat give products a longer shelf life but raises bad cholesterol (LDL) ❖ Complete hydrogenation is avoided because a completely saturated fatty acid is hard and brittle http://chemwiki.ucdavis.edu/Biological_Chemistry/Lipids/Hydrogenation_of_Unsaturated_Fats_or Trans_ Fat Halogenation ❖ Halogens (Br2 and I2) can be added to unsaturated fatty acids at room temperature in acetic acid Oxid ation (b)With KMnO 4  Oxidative Rancidity ❖Highly unsaturated oils are spontaneously oxidized by atmospheric oxygen and ordinary temperatures…olive oil is less susceptible to oxidative rancidity …flax seed oil is more susceptible to oxidative rancidity ❖ This is a slow reaction → short chain fatty acids and aldehydes resulting in a rancid odour or taste to the fats Lipids  Functions of Lipids ❖ Storage form of energy ❖ They are insoluble and can act as food storage ❖ Membrane structure involvement ❖ They have high insulating capacity ❖ Absorption and transport of fatty acids (phospholipids) ❖ They play a role in hormone synthesis (cholesterol) ❖ They are carriers of fat soluble vitamins (Vit. A, D, E,K) ❖ Antibiotic agent (squalamine – steroid found in sharks) ❖ Lipids aid to “waterproof ” us  Classification of Lipids ❖ Lipids can be classified as – (a) Simple lipids/homolipids – e.g. triacylglycerol (triacylglycerol), oils and waxes (a) Compound lipids/ heterolipids – e.g. phospholipids and glycolipids, (b) Derived Lipids - they are derived from simple and compound lipids e.g. steroids, eicosanoids and fat soluble vitamins Simple Lipids: triacylglycerol/triacylglycerols ❖ They are the most abundant of all lipids ❖ Make up 98% of total dietary lipids (remaining 2 %: phospholipids and cholesterol) ❖ Major component of fat storage in plant and animal cells (adipocytes) (triacyglycerol are much better adapted than glycogen to serve as a storage form of energy…longer to digest…greater satiety value) ❖ They are non polar and are therefore insoluble in water ❖ They are less dense than water → floats ❖ It is formed via esterification - reaction between an alcohol (glycerol) and a tricarboxylic acid ❖ Triacylglycerol can undergo hydrolysis to form free glycerol and fatty acids  Chemical Nature ofTriacylglycerol ❖ The chain lengths of the fatty acids in naturally occurring triacylglycerol vary, but most contain 16, 18, or 20 carbon atoms  Functions of Triacylglycerol/Fats ❖ They store long term energy The provide more energy per gram (9 kcal/gram) than proteins or carbohydrates (~4.0 kcal/gram) ❖ They have greater satiety value than carbohydrates ❖ They act as insulators for the body ❖ FACT! The human body has enough fat to make 7 bars of soap ❖ They act as shock absorbers for organs ❖ May make up more than 90% of the cytoplasm ❖ % fat women 25 – 31 % and males 18 – 24 % ❖ The % fat stored is sufficient to allow us to survive 2 -3 months. Glycogen only provides 1 day of energy  Functions of Triacylglycerol /Fats ❖ When the body has used up the calories from carbohydrates… (occurs after the first 20 minutes of exercise), it begins to depend on the calories from fat. ❖ Healthy skin and hair are maintained by fat. Fat helps the body absorb and move the vitamins A, D, E, and K through the bloodstream ❖ About 98% of the lipids in our diet are triacylglycerol, the remaining 2% consists of complex lipids and cholesterol ❖ triacylglycerol cannot pass through cell membranes freely. Enzymes called lipoprotein lipases must break down triacylglycerol into free fatty acids and glycerol.The hormone glucagon stimulates the process ❖ The lipid is first emulsified by bile salts produced in the liver ❖ The glycerol component of triacylglycerol can be converted into glucose for brain fuel Functions of Triacylglycerol  The amount of fat in the diet, especially saturated fat is a health concern …High levels of triacylglycerol in the bloodstream may result in atherosclerosis (hardening of the arteries) resulting in the risk of heart disease and stroke  Waxes ❖ They are esters of long chain saturated and unsaturated fatty acids ❖ Vertebrates:They are secreted by cutaneous glands as a protective coating to keep skin pliable, lubricated and waterproof ❖ Waxes are used in cosmetics, polishes and ointments  Compound Lipids: Phospholipids ❖ They are the most abundant membrane lipids ❖ They differ from triacylglycerol having one polar head and two hydrophobic tails ❖ They are the structural components of the membrane (never stored in large amounts) ❖ Cell membranes separate the cell from the external environment and provide selective transport for nutrients and waste in and out of the cell ❖ Most lipids in the bilayer contains at least one unsaturated fatty acid ❖ This prevents the tight packing of the hydrophobic chain in the lipid bilayer giving fluid- like character to the membranes ❖ This property allows metabolic by-products to cross the cell membrane  Industrial Importance of Phospholipids ❖ Phospholipids have been commercially available as dietary supplements clinically proven safe and beneficial for the brain, liver, circulation, and intestinal tract ❖ Phospholipids are used for processing food and other products as it aids in the mixing of vegetable oils, butters, and other fatty ingredients so that they are uniformly distributed  Compound Lipids: Phospholipids ❖ There are two main types of phospholipids (a)phosphoglycerides – most common (b)sphingolipids ❖ The bipolar nature of phospholipids allows for the formation of bimolecular sheets (bilayers) http://www.bioteach.ubc.ca/Bio-industry/Inex/graphics/lipidbilayer.gif  Phosphoglyceride: Lecithin ❖Found in yeasts and oil seeds (soybean) ❖ Glandular and nervous tissues rich in these lipids ❖ They are required for the transport and utilization of other lipids…In its absence accumulation of lipids occur in the liver which can lead to cirrhosis ❖ It is able to emulsify (break up) fats in the bloodstream, enabling them to pass through the cell walls to be utilized for energy ❖ By emulsifying fats and helping in absorption for use by the body, lecithin will reduce the cholesterol level in the blood http://www.elmhurst.edu/~chm/vchembook/images/553lecithin.gif  Sphingolipids ❖ Sphingolipids are a class of lipids containing a backbone of sphingoid bases, where the alcohol portion is sphingosine ❖ A long chain fatty acid is connected to the amino group by an amide bond and the – OH group at the end of the chain is esterified by phosphorylcholine ❖ The combination of fatty acid and sphingosine is called the ceramide/cerebroside portion http://chemistry.gravitywaves.com/CHE450/Images14-20/Sphingomyelin.gif  Sphingomyelins ❖ Found in nerve tissues (myelin sheath) ❖ The myelin sheath consists of about 70% lipid and 30% protein in the lipid bilayer ❖ They differ from other lipids in that they lack glycerol in the structure ❖ The myelin sheath allows for insulation and rapid conduction of electrical signals ❖ Neimann-Pick Disease- is caused by a deficiency of an enzyme that breaks down excessive sphingomyelin which are therefore stored in the brain, spleen, marrow in large quantities causing mental retardation and blindness  Industrial Importance of Sphingolipids ❖ Mammalian sphingolipid metabolites, such as ceramide and sphingosine-1- phospate, are important mediators in the signaling cascades involved in apoptosis, proliferation, immunoregulation and stress responses ❖ Sphingolipids are used in the preparation of a cosmetic or dermopharmaceutical composition protecting the skin and hair…it modulates the proliferation of skin cells … sphingosine-1-phospate is active at very low concentration, bioavailability to humans is a concern…high concentration of the molecule is seen in persons with ovarian cancer and increases the migration of cancerous cells. ❖ Dietary sphingolipids are used to lower plasma cholesterol and triacylglycerol and prevent liver steatosis (fatty liver- large droplets of fat, containing mostly triacylglycerol, collect within cells of the liver) Compound Lipids: Glycolipids ❖ These comprise of lipids linked to carbohydrates ❖ The carbohydrate portion forms a polar head ❖ They are an important constituent of cell membranes, particularly in the myelin sheath and outer surface of the nerve cells and the chloroplast membrane ❖ Both phospholipids and glycolipids form self-sealing lipid bilayers that are the basis of all cellular membranes  Compound Lipids: Glycolipids https://2012books.lardbucket.org/books/introduction-to-chemistry-general-organic-and- biological/section_20/d1a53e8dae080c3e3ea9700f4e4e8d24.jpg Structures of Glycolipids  Derived Lipids: Steroids (cholesterol) ❖ It is the most abundant steroid ❖ It is absent from plant cells, which is why vegetable oil is considered as cholesterol free…Found in the blood of all animals…Blood plasma levels range from 15 – 250 mg/100mls ❖ It is an important component of cell membrane ❖ Important precursor of many biological compounds e.g. bile acids and steroid hormones ❖ The end products of cholesterol metabolism → steroids (bile salts) ❖ Bile salts are formed in the liver and secreted into the small intestines to absorb lipids ❖ When the bile salts are attached to the lipid the complex is called a chylomicron ❖ Bile salts are largely reabsorbed during lipid absorption  Derived Lipids: Steroids (cholesterol) ❖Cholesterol is acquired by the body in two ways - (a) Production in the cells of the body (b) Dietary sources e.g. meat and dairy products ❖ Sites of production includes – liver, gonads, adrenal glands, nervous tissues and intestines ❖Cholesterol exist in the free and esterified form ❖Many steroid hormones are formed from cholesterol: Aldosterone, Progesterone, Cortisol, Testosterone, Estradiol  Lipoprotein ❖ Cholesterol is insoluble in blood, for transport in an aqueous medium, sterols and other lipids are bound to specific proteins, forming lipoprotein particles ❖ It travels in the blood bound to lipoproteins… These particles are classified based on their composition and density  Lipoproteins – contains lipid surrounded by hydrophilic molecules such as proteins and phospholipids  Lipoprotein ❖ There exist five kinds of lipoproteins, these include ❖ High density lipoprotein (HDL) removes excess cholesterol from the cell and returns it to the liver where it is metabolized to bile acids and salts that are eventually eliminated through the intestine ❖ Low Density lipoproteins (LDL) contain a large amount of cholesterol and cholesteryl esters. Its main function is to delivers cholesterol to the cell to be used mostly as a membrane component  Lipoprotein ❖ Intermediate Density Lipoproteins (IDL) have density in between the HDL and LDL and are responsible for the transport of cholesterol and triacylglycerol ❖ Very Low Density Lipoprotein (VLDL) is synthesized by the liver. Its main purpose is to deliver triacylglycerol, cholesteryl esters and cholesterol to the peripheral tissues ❖ Chylomicrons have the lowest lipid to protein ratio and hence the lowest density. They are synthesized by the absorptive cells of the intestinal lining and are secreted by these cells into the lymphatic system which joins the blood circulation.They carry dietary lipids synthesized in the intestine to the heart muscle, skeletal muscle, adipose tissue and lactating mammary tissue  Derived Lipids: Cholesterol ❖ HDLs carry LDLs away from artery walls ❖ LDL sticks to the artery walls and can lead to plaque build up (atheriosclerosis) ❖ Higher proportion of LDL compared to HDL → associated with cardiovascular diseases such as heart attack and stroke ❖ Diet and exercise help to maintain balance in the LDL and HDL ❖ Two important cholesterol diseases (a)Familial hypercholesterolemia : Over production of cholesterol (b)Zanthomatosis: Build up of cholesterol in the skin  Terpenoids ❖ Terpenoids are a large and diverse class of naturally occurring organic chemicals ❖ Most terpenoids are multicyclic structures that differ from one another not only in functional groups but also in their basic carbon skeletons ❖ Essential oils can be obtained from plants by heating or applying steam distillation to certain plant material. These can be used in medicine or in the perfume industry Biological Importance ofTerpenoids ❖ The steriods and sterols in animals are biologically produced from terpenoid precursors ❖ Sometimes terpenoids are added to proteins, e.g., to enhance their attachment to the cell membrane; this is known as isoprenylation Industrial Importance of Terpenoids ❖ Plant terpenoids are used extensively for their aromatic qualities ❖ Terpenoids play a role in traditional herbal remedies and are under investigation for antibacterial, antineoplastic, and other pharmaceutical functions ❖ Terpenoids contribute to the scent of eucalyptus, the flavors of cinnamon, cloves, and ginger, and the color of yellow flowers ❖ Well-known terpenoids include citral, menthol, camphor and the cannabinoids found in Cannabis  Eicosanoids ❖ Eicosanoids differ from true hormones in that they are produced in small amounts by all cells rather than by specialized cells ❖ Eicosanoids are not stored, they have an extremely short half life, being rapidly metabolized to inactive products ❖ The compound constitutes 20 C atoms (eicosa – means 20) ❖ Arachidonic acid is formed from linoleic acid and linolenic acid https://www.researchgate.net/publication/323845156/figure/fig2/A S:651723450376193@1532394387315/Linoleic-acid- metabolism-yielding-arachidonic-acid.png  Eicosanoids ❖ Eicosanoids are classified into two main groups 1. Prostaglandins, Thromboxanes 2. Leukotrienes ❖ Eicosanoids are involved in complex control reactions in inflammation, immunity and as CNS messengers ❖ They affect many of the body’s functions, example in heart disease, levels of triacylglycerol and arthritis ❖ Prostaglandins, leucotrienes and thromboxanes are produced “at the site” are considered “local hormones” Prostaglandins ❖ Prostaglandins can lower blood pressure ❖ Clinical use of prostaglandins is in uterine contractions and to stop postpartum bleeding ❖ Causes vasodilation ❖ Inhibits platelet aggregation ❖ Control inflammation and vascular permeability Leukotrienes ❖ Over production occurs in asthma and allergic rhinitis ❖ Contraction in smooth muscles lining bronchioles ❖ Regulators of allergic reactions Thromboxanes ❖ Aid in blood clotting; Reduce blood flow to the site of a clot EICOSANOID STRUCTURES