Biochemistry Chapter 19: Lipids - PDF

Welcome to Biochemistry Question 1: What are they? Lipids, carbohydrates, nucleic acids and proteins Characterize the molecule. Functional groups Biological functions Role in a living system  Welcome to Biochemistry Question 2: How are they synthesized? The centr...

Welcome to Biochemistry Question 1: What are they? Lipids, carbohydrates, nucleic acids and proteins Characterize the molecule. Functional groups Biological functions Role in a living system  Welcome to Biochemistry Question 2: How are they synthesized? The central dogma  Welcome to Biochemistry Question 3: How are they metabolized in our bodies? Chapter 19 Lipids Lipid categorization Hydrolyzable lipids can be converted into smaller molecules by hydrolysis. Lipids Nonhydrolyzable lipids cannot be cleaved into smaller molecules by aqueous hydrolysis. Hydrolyzable lipids Hydrolyzable lipids are derived from fatty acids. Fatty acids are carboxylic acids (RCOOH) with long carbon chains of 12 to 20 C atoms. Fatty Acids The Most Abundant Fatty Acids in Animal Fats, Vegetable Oils, and Biological Membranes. Fatty Acids (FAs) They contain an ______ (even/odd) number of carbon atoms. Structural difference between saturated FAs and unsaturated FAs _____________ Naturally occurring unsaturated fatty acids contain _____ (cis/trans) double bonds. Monounsaturated FA has ______ double bonds and polyunsaturated FA (PUFA) has ______ double bonds. As the number of double bonds in the fatty acid increases, the melting point _______ Unsaturated Fatty Acids Unsaturated Fatty Acids Linoleic acid is called an omega-6 acid, because of the position of the first C=C in the nonpolar chain. Linolenic acid is called an omega-3 acid, because of the position of the first C=C in the nonpolar chain. Lipid categorization Waxes Waxes are esters formed from a fatty acid and a high molecular weight alcohol. Waxes Formation of spermaceti wax, isolated from the heads of sperm whales. Waxes Like other esters, waxes are hydrolyzed with water in the presence of acid or base to re-form the carboxylic acid and alcohol from which they were prepared. Practice Draw the carboxylic acid and alcohol products that are formed when wax, CH3(CH2)14COO(CH2) 11CH3 is treated with aqueous sulfuric acid. What is the common name of the carboxylic acid (fatty acid) product? Lipid categorization Triglycerides (fats and oils) Triacylglycerols (triglycerides) are three esters formed from glycerol and three molecules of fatty acids. Triglycerides (fats and oils) Simple triacylglycerols have three identical fatty acid side chains. Mixed triacylglycerols have two or three different fatty acids. Triglycerides (fats and oils) Increase blood cholesterol level Decreases blood cholesterol level Animal fats contain mainly ____________ triglycerides, which are _____ at room temp. Vegetable oils contain ____________ triglycerides, which are ______ at room temp. Hydrolysis of Triacylglycerols Triacylglycerols are hydrolyzed with water in the presence of acid, base, or enzymes (in the body). lipase Hydrolysis of Triacylglycerols – soap synthesis Hydrolysis of Triacylglycerols Practice Identify the products formed from the hydrolysis of the following triacylglycerol in the presence of aqueous sulfuric acid. Practice Draw the skeletal structure of the products formed from the hydrolysis of the following triacylglycerol in the presence of aqueous NaOH. Lipid categorization Phospholipids Phospholipids are lipids that contain a P atom. Two common types of phospholipids are phosphoacylglycerols and sphingomyelins. Phosphoacylglycerols Structurally, they resemble a triacylglycerol with a phosphodiester bonded to an alcohol replacing the third fatty acid. Phosphoacylglycerols One of the main types of phosphoacylglycerols is cephalin (or phosphatidylethanolamine): Phosphoacylglycerols The second of the main types of phosphoacylglycerols is lecithin (or phosphatidylcholine): Phosphoacylglycerols The two fatty acid side chains form two nonpolar “tails” that lie parallel to each other. The phosphodiester end of the molecule is a charged or polar “head”. Phosphoacylglycerols Phosphoacylglycerols are the main component of most cell membranes. Sphingomyelins Sphingomyelins do not contain a glycerol backbone, they have a sphingosine backbone instead. Sphingomyelins do not contain an ester; their single fatty acid is bonded to the backbone by an amide bond. Sphingomyelins The myelin sheath, the coating that surrounds nerve cells, is rich in sphingomyelins. Sphingomyelins An example of sphingomyelin: Practice What kind of molecule is this? Write down the common (not IUPAC) names of those smaller molecules. Practice What kind of molecule is this? Write down the common (not IUPAC) names of those smaller molecules. Cell membrane Cell membrane is selectively permeable: Acts as a barrier to stop the passage of ions and molecules into or out of the cell. Allow nutrients in and waste out. Cell membrane Phospholipids are the major component of cell membranes When phospholipids are mixed with water, they assemble into a lipid bilayer. Cell membrane components glycoproteins glycolipids Transport across cell membrane Transport across cell membrane Transport across cell membrane Larger polar molecules need facilitated transport to cross efficiently. Transport across cell membrane Practice Which of the following transport moves against the concentration gradient? A. Diffusion B. Facilitated transport C. Active transport Lipid categorization Steroids Steroids are a group of lipids whose carbon skeletons contain several fused rings: Steroids-cholesterol Cholesterol, the most prominent steroid, is synthesized in the liver and found in almost all body tissues. It is obtained in the diet from many sources, including meat, cheese, butter, and eggs.  Lipoproteins Lipoproteins: are carriers (transporters) of cholesterol. Why does cholesterol need carriers? Most lipoproteins contain a core of hydrophobic lipid molecules surrounded by a shell of hydrophilic molecules such as proteins and phospholipids.  Lipoproteins There are four kinds of lipoproteins. High-density lipoprotein (HDL) (“good cholesterol”), which consists of about 33% protein and 30% cholesterol. Low-density lipoprotein (LDL) (“bad cholesterol”). which contains about 25% protein and 50% cholesterol.  Lipoproteins chol Low-density lipoproteins (LDLs) transport cholesterol from the liver to the tissues. High-density lipoproteins (HDLs) transport cholesterol from tissues back to the liver.  Levels of LDL and HDL If there are sufficient LDL receptors on the surface of cells, LDL is effectively removed from circulation and its concentration in blood plasma drops. The number of LDL receptors is controlled by a feedback mechanism.  Levels of LDL and HDL When the concentration of cholesterol inside cells is high, the synthesis of LDL receptors is suppressed so less LDL is taken into the cell from the plasma and the LDL level in the plasma rises (and vice versa). LDLs deposit cholesterol on the walls of arteries  Levels of LDL and HDL This forms plaque, which restricts blood flow; LDL cholesterol is called “bad” cholesterol. HDLs reduce the level of cholesterol in the bloodstream by bringing excess back to the liver; HDL cholesterol is called “good” cholesterol. HDL levels can be increased by exercise and weight loss.  Synthesis of Cholesterol The serum cholesterol level controls the amount of cholesterol HMG-CoA synthesized by the liver. When serum cholesterol is high, its synthesis in the liver is low, and vice versa. The commonly used statin drugs inhibit the synthesis of cholesterol by blocking one of the key enzymes, called HMG-CoA reductase, in cholesterol synthesis. Lipid categorization Vitamins Vitamins are organic compounds required in small quantities for normal metabolism and must be obtained from the diet. Vitamins are either water soluble or fat soluble. Fat-soluble vitamins The four fat-soluble vitamins (A, D, E, and K) are found in fruits, vegetables, fish, liver, and dairy products. They are stored in adipose cells to be used when needed. Fat-soluble vitamins Vitamin A is found in liver, fish, and dairy products, and is made from β-carotene. It is needed for vision and for healthy mucous membranes. Vitamin A deficiency causes night blindness and dry eyes and skin. Fat-soluble vitamins Vitamin D can be synthesized from cholesterol. It can be obtained in the diet from many foods, especially milk, and helps regulate Ca and K metabolism. A deficiency of vitamin D causes rickets (bone malformation). Fat-soluble vitamins Vitamin E is an antioxidant, protecting unsaturated side chains in fatty acids from unwanted oxidation. Deficiency of vitamin E causes numerous neurological problems, although it is rare. Fat-soluble vitamins Vitamin K regulates the synthesis of clotting proteins (prothrombin), and deficiency of this leads to excessive or fatal bleeding. Lipid categorization Prostaglandins and leukotrienes  Prostaglandins Prostaglandins: A group of fatty-acid-like substances that have the 20-carbon skeleton of prostanoic acid. 1 7 5 3 prostanoic acid: 9 COOH 8 6 4 2 10 12 14 16 18 20 11 13 15 17 19  Prostaglandins Prostaglandins are not stored in tissues as such but are synthesized from membrane-bound 20-carbon polyunsaturated fatty acids (such as arachidonic acid) in response to specific physiological triggers. arachidonic acid  Prostaglandins  Prostaglandins are synthesized from arachidonic acid by a ring closure at carbons 8 and 12. The enzyme Cyclooxygenase (call COX for short) catalyzes this reaction. 9 8 6 5 COOH 11 12 14 15 Arachidonic acid PGH2:Prostaglandin H2 PGE2:Prostaglandin E2 PGF2a :Prostaglandin F2a Prostaglandins PGE2:Prostaglandin E2 PGE2 lowers blood pressure by relaxing the muscle cells inside blood vessels PGF2a :Prostaglandin F2a PGF2α stimulates uterine contractions and induce labor  COX Enzymes The COX enzyme occurs in two forms: COX-1 catalyzes the normal physiological production of prostaglandins. COX-2 is responsible for the production of prostaglandins in response to inflammation.  COX Enzymes Nonsteroidal anti-inflammatory drugs (NSAIDs) such as aspirin and ibuprofen inhibit both COX enzymes – an undesirable side effect. Drugs sold as Vioxx, Bextra, and Celebrex block only the COX-2 enzyme without affecting gastric secretions.  Leukotrienes Leukotrienes are also synthesized from arachidonic acid. They occur mainly in white blood cells (leukocytes). (LTB4) They cause inflammation and fever. zileuton 5-lipoxygenase They produce muscle contractions, especially in the lungs, and thereby can cause asthma-like attacks. Leukotrienes Anti-asthma drugs like zileuton inhibit the synthesis of leukotrienes. Practice Classify the following compounds