Lipids 2024 PDF

23/10/24 MBIO 2100 LIPIDS: Lehninger Principles of Biochemistry A diverse group of organic...

23/10/24 MBIO 2100 LIPIDS: Lehninger Principles of Biochemistry A diverse group of organic molecules that have low solubility LIPIDS in water (hydrophobic). Text and figures from Lehninger 3rd - 7th ed., WHAT ARE THEIR FUNCTIONS? unless otherwise noted. Barbara H. Zimmermann, Ph.D. 1 2 Functions of lipids Functions of lipids Other lipids: enzyme cofactors Fats, oils: stored forms of energy (storage lipids) electron carriers (example?) light absorbing pigments Phospholipids, sterols: structural/protection major structural elements of membranes hydrophobic anchors emulsifying agents in digestion hormones intracellular messengers 3 4 Functions of lipids - electron carrier Functions of lipids - pigment Hydrophobic quinone Lipids can provide pigment ubiquinone = coenzyme Q, Q diffuses in membrane carries electrons between less mobile carriers. can accept 1 or 2 electrons. 5 6 1  23/10/24 Functions of lipids - photopigment Functions of lipids - wax photopigments, chlorophyll a, chlorophyll b Triacontanoyl palmitate is the major componenet of beeswax. Biological waxes = Esters of long-chain fatty acids with long chain alcohols. Waxes have diverse functions: metabolic fuel for plankton The alternating double and single bonds (pink) water-repellent protection for feathers are responsible for absorbing visible light. protection aganst water evaporation for leaves. 7 8 Functions of lipids - wax Functions of lipids The spermaceti organ: ~ 1/3 of total whale weight ~ 3,600 kg of spermaceti oil (triacylglycerols + waxes) Triacontanoyl palmitate is the major componenet of beeswax. “The principal function of the spermaceti organ and its Biological waxes = associated structures (the junk, air sacs and passages, Esters of long-chain fatty acids with long chain alcohols. and the museau de singe clapper system at the front of the organ) …is to form, and focus, the sperm whale’s Waxes have diverse functions: ester click making an extremely powerful ECHOLOCATION R R metabolic fuel for plankton system” Hal Whitehead, in Encyclopedia of Marine Mammals (2018, 3rd water-repellent protection for feathers Edition). protection aganst water evaporation for leaves. 9 10 Naming fatty acids Naming fatty acids Chain length:number of double bonds(Ddouble bond positions) The carboxylic carbon is C-1 The prefix “n-” indicates “normal” (= unbranched) chain Example: 20:2 (D9,12) Fatty acids (ácidos grasos) = carboxylic acids with hydrocarbon chains of C4 to C36. 20 carbon fatty acid Fully saturated (saturado) = no double bonds Two double bonds Unsaturated (insaturado) = contains double bonds between C-9 and C-10 usually in cis configuration between C–12 and C-13 almost never conjugated (alternating single bond double bonds). 11 12 2  23/10/24 Naming fatty acids Naming fatty acids Chain length:number of double bonds(Ddouble bond positions) Chain length:number of double bonds The carboxylic carbon is C-1 (Ddouble bond positions) The prefix “n-” indicates “normal” (=unbranched) The carboxylic carbon is C-1 chain Example: 18:0 name this fatty acid ––––––––––> n-octadecanoic acid 13 14 Naming fatty acids Naming fatty acids Chain length:number of double bonds Chain length:number of double bonds - (Ddouble bond positions) (Ddouble bond positions) The carboxylic carbon is C-1 The carboxylic carbon is C-1 name this fatty acid ––––––––––> 18:2 (D 9,12) D9 18:1 ( ) An 18 carbon fatty acid with one double bond between C-9 and C-10 15 16 Physical properties Physical properties Fully saturated fatty acids. Tight packing. All chains fully extended in van der Waals contact. Melting point is higher: More thermal energy required to disrupt the many interactions. Unsaturated fatty acids Less ordered packing. Which mixture has a higher melting point? Double bonds cause bends in the chains. Melting point is lower: fewer Explain why. interactions must be disrupted. 17 18 3  23/10/24 18:0 CH3(CH2)16COOH n-octanedecanoic acid 69.6 °C 18:1(D9) (CH2)7CH=CH(CH2)7COOH cis-9-octanedecanoic acid 13.4 °C MELTING POINT MELTING POINT Physical properties Physical properties 19 20 Physical properties Physical properties 21 22 Storage lipids Storage Lipids low oxidation state (= highly reduced) derivatives of fatty acids can be oxidized in highly exergonic reactions Most common fatty acids have an even number of carbons (because they are synthesized from 2 carbon examples: triacylglycerols units). Physical properties 23 24 4  23/10/24 Storage lipids Storage lipids Triacylglycerols Triacylglycerols = triglycerides, fats, neutral fats (Triacilgliceroles) Simple triacylglyceride – The 3 fatty acids are the same. Mixed triacylglyceride – Esters of long-chain The 3 fatty acids are different. fatty acids with (most common in nature) glycerol. R ester 25 26 Storage lipids Storage lipids Fats Provide Efficient Fuel Storage Humans have fat tissue (mostly adipocytes) (a) under the skin Cross section of (b) in the abdominal cavity human white adipose (c) mammary glands. tissue. Each cell contains a Moderately obese people (15 -20 kg of fat tissue) could live for months from their stored fat droplet (white) so fat. large that it squeezes the nucleus (stained red) against the The human body can store < 1 day’s energy supply in the form of glycogen. plasma membrane. 27 28 Storage lipids Fats in food Advantages of storing energy as fat Most foods are complex instead of carbohydrate: mixtures of simple and mixed triacylglycerols. Fatty acids more reduced than carbohydrate saturated fat > 2X more energy per gram. melting point Triacylglycerols not hydrated, weight does not include H2O (compare: 2 g H2O / g polysaccharide). SATURATED UNSATURATED 29 30 5  23/10/24 Fats in food Fats in food Phospholipids, triacylglycerols, and cholesterol LDLs = low-density lipoproteins are are essentially insoluble in water, and are "bad" cholesterol carried in the blood as plasma lipoproteins. carry cholesterol to the tissues Plasma lipoproteins are complexes of: increased LDL is linked to increased risk for heart disease Apolipoproteins that are specific lipid carrier proteins HDLs = high-density lipoproteins Combinations of different lipids. "good" cholesterol There are several different classes of plasma carry excess cholesterol to the liver lipoproteins, each having different functions. liver processes and excretes cholesterol examples: HDLs and LDLs increased HDL lowers risk for heart disease http://www.webmd.com/content/article/11/1671_50422.htm 31 32 Fats in food Electron Microscope Pictures of Lipoproteins saturated fat causes LDL and HDL “Eating foods with a lot of saturated fat raises your risk for heart disease; this causes the amount of “bad” LDLs in your blood to increase while “good” HDLs decrease. Cut the saturated fat, and your blood-cholesterol levels and your risk for heart disease drop. Your risk for cancer Named based on position of sedimentation also decreases.” (density) in centrifuge Large enough to see in electron microscope http://www.webmd.com/content/article/11/1671_50422.htm 33 34 Fats in food Fats in food “… Hydrogenated fats [trans fatty acids, TFAs] are liquid vegetable oils made creamy when manufacturers convert some of the unsaturated fats into saturated ones through a process called “Libre de Trans” "hydrogenation.” hydrogenation http://www.webmd.com/content/article/11/1671_50422.htm 35 36 6  23/10/24 Fats in food Fats in food … TFAs raise blood-cholesterol levels and increase partial hydrogenation reconfigures most of the heart-disease risk just like saturated fats.” double bonds that do not become chemically http://www.webmd.com/content/article/11/1671_50422.htm saturated...to the trans configuration…” PARTIAL hydrogenation + unsaturated trans http://en.wikipedia.org/wiki/Trans_fat https://authoritynutrition.com/why-trans-fats-are-bad/ 37 38 Fats in food saturated fats cause: LDL and HDL trans fats cause: LDL and HDL inflammatory response https://www.who.int/news-room/commentaries/detail/trans-fat-eliminate-this-invisible- killer-from-the-world-s-food-supply 39 40 WHO Report on Global Trans Fat Elimination 2021 Structural lipids Structural lipids form membranes. Membrane lipids are amphipathic (= one end of molecule is hydrophilic, the other end is hydrophobic). Membranes are double layers of lipids (bilayers) act as a barrier to passage of polar molecules and ions. Membranes contain: bicapa the United States classify 61 62 Eicosanoids Eicosanoids aspirin (acetyl salicylate) Figure 10.69 from Devlin, Textbook of Biochemistry with Edward Stone, clinical correlations, 1763, bark of willow 2002. tree (corteza del sauce). NSAID = nonsteroidal anti-inflammatory drugs AINE = antiinflamatorios no esteroideos Phospholipase A2 inhibitors: hydrocortisone, prednisone, betamethasone. wikipedia Cyclooxygenase inhibitors: Aspirin, phenylbutazone 63 64 Vitamin D Vitamin D Vitamin D Formed in the skin by UV radiation of 7- dehydrocholesterol (pink bond is broken). The active hormone, 1, 25- dihyrdoxycholecalciferol regulates the metabolism of Ca2+ in: Vitamin D Økidney metabolism. ØIntestine ØBone 65 66 11  23/10/24 Vitamin D LIPIDS Diverse organic molecules with low solubility in H2O. Functions: stored source of energy, structural component of membranes, many other functions. Naming fatty acids. Ether and ester linkages. Physical properties related to saturation/unsaturation. Storage lipids (neutral) Triacylglycerols rickets (raquitismo) is caused by deficiency in Saturated/unsaturated fats in foods. vitamin D, and leads to defective bone HDLs and LDLs formation. Trans fats, how produced and why unhealthy. 67 68 LIPIDS Structural lipids (amphipathic): Phospholipids: phosphatidic acid precursor, phospholipids, plasmalogen. Glycolipids: sphingolipids, human blood groups, Tay Sachs Examples of signaling molecules: Steroids: cholesterol Eicosanoids: paracrine hormones, prostaglandins, NSAIDs Example of a cofactor: Vitamin D. 69 12