CHEM113 – LECTURE COVERAGE 1. Cell 2. Carbohydrates 3. Proteins 4. Lipids - - 1. 2. 3. 4. 5. 6. - - CELL The basic structural and functional unit of living organisms. Make up living things and carry out activities that keep a living thing alive. Cell Theory A collection of ideas and conclusions from many different scientists over time that describes cells and how cells operate. Robert Hooke (1665) – discovered cell Anton Van Leeuwenhoek (1674) – observed living cell Robert Brown (1883) – discovered nucleus Felix Dujardin (1835) – discovered fluid content of cell Matthias Schleiden (1838) – proposed all plants are made up of cells. J.E. Purkinje (1839) – named fluid content of cell as protoplasm. Unicellular Organisms made up of only one cell Ex: Euglena, Paramecium, Yeast Multicellular Organisms Made up of more than one cell Ex: Plants, animals, fungus Size of Cells - Most cells are very small (microscopic), some may be very large (macroscopic) - The unit used to measure size of a cell is micrometer - 1 μm = 1/1000 millimeter - Nerve cells are branched to conduct impulses from one point to another Human WBCs can change their shape to engulf the microorganisms enter the body. Structure of Cell The detailed structure of a cell has been studied under compound microscope and electron microscope Certain structures can be seen only under an electron microscope. The structure of a cell as seen under an electron microscope is called ultrastructure. Compound microscope – 2000x Electron microscope – 500,000x Animal Cell Plant Cell Shape of Cells Variation depends mainly upon the function of cells Some cells like euglena and Amoeba can change their shape, but most cells have a fixed shape. Human RBCs are circular biconcave for easy passage through human capillaries Aki | 1 CHEM113 – LECTURE Bacterial Cell Structure of Cell Plasma Membrane - Extremely delicate, think, elastic, living and semipermeable membrane - Made up of two layers of lipid molecules in which protein molecules are floating - Thickness varies from 75-110 A - Can be observed under an electron microscope only Functions: Maintain shape and size of the cell Protects internal contents Regulates entry and exit of substances in and out of the cell Maintains homeostasis Cell Wall - Non-living and outermost covering of a cell (plants and bacteria) - Can be tough, rigid and sometimes flexible - Made up of cellulose, hemicellulose and pectin - May be thin or thick, multilayered structure - Thickness varies from 50-1000 A Functions: Provides definite shape, strength and rigidity Prevents drying up (desiccation) of cells Helps in controlling cell expansion Protects cell from external pathogens Nucleus - Dense spherical body located near the center of the cell - Diameter varies from 10-25 μm - Present in all the cells except red blood cells and sieve tube cells - Well developed in plant and animal cells - Undeveloped in bacteria and blue-green algae (cyanobacteria) - Most of the cells are uninucleate (having only one nucleus) - Nucleus has a double layered covering called nuclear membrane - Nuclear membrane has pores of diameter about 80-100 nm - Colorless dense sap present inside the nucleus known as nucleoplasm - Nucleoplasm contains round shaped nucleolus and network of chromatin fibers - Fibers are composed of deoxyribonucleic acid (DNA) and protein histone - These fibers condense to form chromosomes during cell division - Chromosomes contain stretches of DNA called genes - Genes transfer the hereditary information from one generation to the next Functions: Control all the cell activities like metabolism, protein synthesis, growth and cell division Nucleolus synthesizes ribonucleic acid (RNA) to constitute ribosomes Store hereditary Information In genes Cytoplasm - Jelly-like material formed by 80 % of water - Present between the plasma membrane and the nucleus - Contains a clear liquid portion called cytosol and various particles - Particles are proteins, carbohydrates, nucleic acids, lipids and inorganic ions - Also contains many organelles with distinct structure and function - Some of these organelles are visible only under an electron microscope - Granular and dense in animal cells and thin in plant cells Endoplasmic Reticulum - Network of tubular and vesicular structures which are interconnected with one another - Some parts are connected to the nuclear membrane, while others are connected to the cell membrane - Two types. Smooth (lacks ribosomes) and rough (studded with ribosomes) Functions Gives Internal support to the cytoplasm RER synthesize secretory proteins and membrane proteins SER synthesize lipids for cell membrane In liver cells SER detoxify drugs & poisons In muscle cells SER store calcium Ions Golgi body - Discovered by Camillo Golgi - Formed by stacks of S-8 membranous sacs - Sacs are usually flattened and are called the cisternae - Has two ends: cis face situated near the endoplasmic reticulum and trans face situated near the cell membrane Functions: Modifies, sorts and packs materials synthesized in the cell Delivers synthesized materials to various targets Inside the cell and outside the cell Produces vacuoles and secretory vesicles Forms plasma membrane and lysosomes Aki | 2 CHEM113 – LECTURE Lysosomes - Small, spherical, single membrane sac - Found throughout the cytoplasm - Filled with hydrolytic enzymes - Occur in most animal cells and in few types of plant cells Functions: Help in digesting of large molecules Protect cell by destroying foreign invaders like bacteria and viruses Degradation of worn-out organelles In dead cells perform autolysis Vacuoles - Single membrane sac filled with liquid of sap (water, sugar and ions) - In animal cells, vacuoles are temporary, small in size and few in number - In plant cells, vacuoles are large and more in number. - May be contractile or non-contractile Functions: Store various substances including waste products Maintain osmotic pressure of the cell Store food particles in amoeba cells Provide turgidity and rigidity to plant cells Mitochondria - Small, rod shaped organelles bounded by two membranes inner and outer - Outer membrane Is smooth and encloses the contents of mitochondria - Inner membrane Is folded in the form of shelf like inward projections called cristae - Inner cavity Is filled with matrix which contains many enzymes - Contain their own DNA which are responsible for many enzymatic actions Functions: Synthesize energy rich compound ATP ATP molecules provide energy for the vital activities of living cells Plastids - double membrane-bound organelles found inside plants and some algae. - They are responsible for activities related to making and storing food. - They often contain different types of pigments that can change the color of the cell. Chromoplasts - produce and store pigments - They are responsible for different colors found in leaves, fruits, flowers and vegetables. Carrot - Pigment: Carotene Mango - Pigment: Xanthophyll Tomato - Pigment: Lycopene Leucoplasts - colorless plastids that store foods. - They are found in storage organs such as fruits, tubers and seeds. Potato tubers - Food: Starch Maize grains - Food: Protein Castor seeds - Food: oil Chloroplasts - Double membrane-bound organelles found mainly in plant cells - Usually spherical or discoidal in shape - Shows two distinct regions-grana and stroma - Grana are stacks of thylakoids (membrane bound, flattened discs) - Thylakoids contain chlorophyll molecules which are responsible for photosynthesis - Stroma is a colorless dense fluid Functions: Convert light energy into chemical energy in the form of food Provide green color to leaves, stems and Vegetables Centrosome - Centrosome is the membrane bound organelle present near the nucleus - Consists of two structures called centrioles - Centrioles are hollow, cylindrical structures made of microtubules - Centrioles are arranged at right angles to each other Functions: Form spindle fibers which help in the movement of chromosomes during cell division Help in the formation of cilia and flagella Cytoskeleton - Formed by microtubules and microfilaments - Microtubules are hollow tubules made up of protein called tubulin - Microfilaments are rod shaped thin filaments made up of protein called actin Functions: Determine the shape of the cell Give structural strength to the cell Responsible for cellular movements Prokaryotic Cell Nucleus is undeveloped Only one chromosome is present Membrane bound organelles are absent Size ranges from 0.5-5 μm Examples: Bacteria and blue green algae Eukaryotic Cell Nucleus is well developed More than one chromosome are present Membrane bound organelles are present Size ranges from 5-100 μm Examples: All other organism Animal Cell Generally small in size Cell wall is absent Plastids are absent Vacuoles are smaller in size and less in number Centrioles are present Plant Cell Generally large in size Cell wall is present Plastids are present Vacuoles are larger in size and more in number Centrioles are absent Aki | 3 CHEM113 – LECTURE CARBOHYDRATES Biochemical substance - It is a chemical substance found within a living organism - These substances are divided into two groups: bioinorganic substances and bioorganic substances - Human uses carbohydrates of the plat kingdom extend beyond food Carbohydrates in the form of cotton and linens are used as clothing Carbohydrates in the form of wood are used for shelter and heating and in making paper 1. 2. 3. 4. 5. 6. - Occurrence and functions The most abundant class or bioorganic molecules on planet earth In plants, it constitutes about 75% by mass of dry plant materials Green (chlorophyll-containing) plants produce carbohydrates via photosynthesis Plants have two main uses, the produce: - Cellulose – serves as structural elements - Starch – provide energy reserves Dietary intake of plant materials is the major carbohydrate source for humans and animals The average human diet should ideally about two-thirds carbohydrates by mass Functions of Carbohydrates in Human Oxidation provides energy Storage, glycogen, provides a short-term every source Supply carbon atoms for the synthesis of other biochemical substances Form part of the structural framework of DNA and RNA molecules Linked to lipids are structural components of cell membranes Linked to proteins function in a variety of cell-cell and cellmolecule recognition process Classification of Carbohydrates Most simple carbohydrates have empirical formula that fit the general formula 𝑪𝒏 𝑯𝟐𝒏 𝑶𝒏 Early observation by scientists that the above-mentioned formula can also be written as 𝑪𝒏 𝑯𝟐 𝑶 𝒏 hydrate of water A polyhydroxy aldehyde, a polyhydroxy ketone or a compound that yields polyhydroxy aldehydes or polyhydroxy ketones upon hydrolysis Monosaccharide Contains a single polyhydroxy aldehyde or polyhydroxy ketone unit - Cannot be broken down into simpler units by hydrolysis (addition of water module) - Pure monosaccharides are water-soluble, white, crystalline solids - Ex: Glucose and Fructose Oligosaccharide - Contains 2-10 monosaccharide units covalently bonded to each other - Disaccharide – most common type of oligosaccharide units covalently bonded to each other - Example: Sucrose (table sugar) - Upon hydrolysis, oligosaccharides and polysaccharides produce monosaccharide units Polysaccharide - Contains many monosaccharide units covalently bonded to each other - Ex: Cellulose, Starch Chirality: Handedness in Molecules Handedness - An important general structure property of most monosaccharide - Two forms: left-handed and right-handed (mirror images) - This property in not restricted to carbohydrates Mirror image - The reflection of an objects in a mirror a) Superimposable mirror image - Coincide at all points when the image is laid upon each other - All are the same b) Nonsuperimposable mirror image - Not all points coincide when the images are laid upon each other - Exists in left-handed and right-handed Not all molecules possess handedness Any organic molecule that contains a carbon atom with four different groups attached to it in a tetrahedral orientation possesses handedness Chiral center – an atom in a molecule that has four different groups tetrahedrally bonded to it a) Chiral molecule – not superimposable b) Achiral molecule – superimposable - Aki | 4 CHEM113 – LECTURE Examples of Chiral Compound: Stereoisomerism: Enantiomers and Diastereomers Stereoisomers - Are isomeric molecules that have the same molecular formula and sequence of bonded atoms but differ in threedimensional orientation of their atoms in space Features that generate stereoisomerism: Presence of a chiral center in a molecule Presence of “structural rigidity” in a molecule Enantiomers - Sometimes called optical isomers - Molecules are nonsuperimposable mirror images of each other - Left and right-handed forms of a molecule with a single chiral center are enantiomers - Came from the Greek word “enantios” meaning opposite Diastereomers - Molecules are not mirror images of each other - Ex: Cis-trans isomers of alkenes and cycloalkanes - Molecules that contain more than one chiral center can also exist in diastereomeric as well as enantiomeric forms Not Chiral Compound: Magkapareho un CH2, ang chiral dapat magkakaiba un atoms. ang tawag daw dyan ay Ethyl Radical hindi na siya tetrahedral (dapat apat ung nakaattach sa carbon) may doble bond siya hindi siya chiral kasi cyclic compound na tawag dito Basta ang chiral compound ay dapat tetrahedral (apat un nakaattach saknya) tapos dapat magkakaiba ung apat na atoms na nakaattach kay carbon. Designating Handedness using Fischer Projection Formulas It is a two-dimensional structural notation for showing the spatial arrangement of groups about chiral centers in molecules Chiral center is represented as the intersection of vertical and horizontal lines The chiral center, which is almost always carbon, is not explicitly shown Aki | 5 CHEM113 – LECTURE Interaction between chiral compounds Enantiomeric pair have the same interaction with achiral molecules and different interactions with chiral molecules 1. Enantiomers have identical: Boiling points Melting points Densities Intermolecular force strength 2. A pair of enantiomers have the same solubility in an achiral solvent, such as ethanol, but differing solubilities in a chiral solvent, such as D-2-Butanol 3. The rate and extent of reaction of enantiomers with another reactant are the same if the reactant is achiral but differ if the reactant is chiral 4. Receptor sites for molecules within the body have chirality associated with them Examples: Spearmint (D-Carvone) and Caraway (L-Carvone) D-Epinephrine (perfect fit with the cellular receptor) and L-Epinephrine - Classification of Monosaccharide The term saccharide comes from the Latin word for sugar, which is saccharum - Only monosaccharide with 3-7 carbon atoms is commonly found in nature Aldose - Monosaccharide that contains an aldehyde functional group - A polyhydroxy aldehyde Ketose - A monosaccharide that contains a ketone functional group - A polyhydroxy ketone - the term saccharide comes from the Latin word for “sugar” which is saccharum - Properties of Enantiomers When plane-polarized light is passed through a solution containing a single enantiomer, the plane of the polarized light is related counterclockwise (to the left) or clockwise (to the right), depending on the enantiomer The extent of rotation depends on the concentration of the enantiomer as well as on its identity The two enantiomers of a pair rotate the plane-polarized light the same number of degrees, but in opposite directions. Additional notations - (+) means rotation to the right (clockwise) - (-) means rotation to the left (counterclockwise) D-L configuration is not directly related to + and – designations. D (+) – Mannose – right-handed isomer that rotates planepolarized light in a clockwise direction (to the right) Optically Active Compound - A compound that rotates the plane polarized light - Achiral compound – are optically inactive - Chiral molecules – optically active Dextrorotatory compound - Chiral compound that rotates the plane of polarized light in a clockwise direction Levorotatory compound - Chiral compound that rotates the plane of polarized light in a counterclockwise direction Biochemically important monosaccharide D-Glyceraldehyde and Dihydroxyacetone - The simplest of the monosaccharides - Are important intermediates in the process of glycolysis Aki | 6 CHEM113 – LECTURE D-Glucose - Ripe fruits are a good source of glucose, which is often referred to as grape sugar - Other names are dextrose and blood sugar - The normal glucose in human blood is in the range of 70-100 mg/dL (1 dL = 100 mL) - Cells use glucose as a primary source of energy D-Galactose - D-Galactose and D-Glucose are epimers (C-4) - Seldom encountered as a free monosaccharide - In human body, it is synthesized from glucose in the mammary glands for use in lactose (milk sugar), a disaccharide consisting of a glucose unit and galactose unit - Also called brain sugar because it a component of glycoproteins (proteincarbohydrate compounds) found in brain and nerve tissue - Also present in the chemical markers that distinguish various types of blood – A, B, AB, and O D-Fructose - Most important ketohexose - Also known as levulose and fruit sugar - The sweetest-tasting of all sugars - Found in fruits and honey - Sometimes used as dietary sugar - Different in C-1 and C-2 with D-Glucose D-Ribose - An aldopentose - A component of a variety of complex molecules such as RNA and ATP - The compound 2 deoxy-Dribose is an important component in nucleic acid chemistry Cyclic forms of Monosaccharides Experimental evidence indicates that for monosaccharides containing five or more carbon atoms, such open-chain structures are actually in equilibrium with two cyclic structures, and the cyclic structures are the predominant forms at equilibrium Recall: Hemiacetals- both –OH and –OR groups are attached to the same carbon atom Monosaccharides – the –OH and –OR groups are attached to the carbonyl carbon The cyclic forms of monosaccharides result from the ability of their carbonyl group to react intramolecularly with a hydroxyl group Cyclization of glucose (hemiacetal) creates a new chiral center at carbon 1, and the presence of this new chiral center produce two stereoisomers, called α and β isomers Pyranose - Contains a six-atom ring Furanose - A five-atom ring Reactions of Monosaccharides 1. Oxidation to acidic sugars 2. Reduction to sugar alcohols 3. Glycoside formation 4. Phosphate ester formation 5. Amino acid sugar formation Oxidation to Acidic Sugars - Monosaccharide oxidation can yield three different types of acidic sugars depending on the oxidizing agent used Weak Oxidizing Agent - Tollen’s and benedict Reagents - Aldoses are converted into aldonic acid Aldoses are reducing sugars - Reduces Ag to Ag in Tollen’s Reagent - Reduces Cu to Cu in benedict reagent A reducing sugar is a carbohydrate that gives a positive test with Tollen’s and Benedict’s solutions In basic conditions, ketoses also give positive results with these reagents Theses tests are used to test glucose in the urine The color of the strip is compared with a chart to determine the concentration of the glucose in the urine sample Strong oxidizing agent - Oxidize both ends of a monosaccharide at the same time to produce a dicarboxylic acid, aldaric acid In biochemistry systems, enzymes can oxidize the primary alcohol end of an aldose to produce alduronic acid Aki | 7 CHEM113 – LECTURE Reduction to produce Sugar Alcohols - The carbonyxl group can be reduced to a hydroxyl group using hydrogen as the reducing agent – sugar alcohols D-Glucitol - Common name is D-Sorbitol that is used as moisturizer in foods and cosmetics - Used as sweetening agent in chewing gum because it cannot be used by bacteria as their food Glycoside formation - Reacting between monosaccharide and an alcohol Glycoside - Is an acetal formed from a cyclic monosaccharide by replacement of the hemiacetal carbon -OH group with an – OR group Phosphate Ester Formation - The hydroxyl group of a monosaccharide can react with inorganic oxoacids to form inorganic esters. - Play important roles in the metabolism of carbohydrates Amino Sugar Formation - One of the hydroxyl group is replaced with an amino group - The three common natural amino sugars: - Amino sugars and their N-acetyl derivatives are important building blocks of polysaccharides found in chitin and hyaluronic acid N-Acetyl-a-D-glucosamine and N-Acetyl-a-Dgalactosamine - Are present in the biochemical markers on red blood cells, which distinguish the various blood types Disaccharides Has cyclic form can react with an alcohol to form a glycoside This is the same process in joining two or more monosaccharide units The most important chemical reaction of maltose is that of hydrolysis producing 2 D-glucose units Acidic condition is needed or maltase is needed If not treated, galactosemia can cause mental retardation in infants and even death. Treatment involved exclusion of milk and milk products from diet The α form of lactose is sweeter to the taste and more soluble in water than the β form The β form can be found in ice cream that has been stored for a long time; its crystallizers and gives the ice cream a gritty texture Glycosidic Linkage - Is the bond in a disaccharide resulting from the reaction between the hemiacetal carbon atom – OH - Always carbon-oxygen-carbon bond Maltose - Often called malt sugar - Comes from the breakdown of starch common ingredient in baby foods and in malted sugar - Made up 2 D-Glucose units - A reducing sugar Cellobiose - Produced as an intermediate in the hydrolysis of the polysaccharide cellulose - Like maltose, cellobiose two D-glucose units but has a β(1→4) glycosidic linkage - Like maltose, cellobiose is a reducing sugar, has three isomeric forms in aqueous solution and upon hydrolysis produces two D-glucose molecules Lactose - Made up of β-D-galactose and a D-glucose unit joined by β(1→4) glycosidic linkage - Principal carbohydrate in milk - Human – 7% - 8% lactose - Cow’s milk – 4%-5% lactose - Lactose intolerance: a condition in which people lack the enzyme lactase needed to hydrolyze lactose to galactose and glucose. - Lactase hydrolyzes β(1-4) glycosidic linkages. - Deficiency of lactase can be caused by a genetic defect, physiological decline with age, or by injuries to intestinal mucosa. 1. 2. 3. 4. - Polysaccharides A polymer that contains many monosaccharide units bonded to each other by glycosidic linkages Polysaccharides are often also called glycans The identity of the monosaccharide repeating unit in the polymer chain Homopolysaccharide Heteropolysaccharide The length of the polymer chain The type of glycosidic linkage between monomer units The degree of branching of the polymer chain Storage polysaccharide a storage form for monosaccharides and is used as an energy source in cells to lower the osmotic pressure within cells the most important storage polysaccharides are starch (in plant cells) and glycogen (in animal and human cells) not sweet and don’t show positive tests with Tollen’s and Benedict’s solutions whereas monosaccharides are sweet and show positive tests limited water solubility Examples: Cellulose, starch in plants Glycogen in animals chitin in arthropods Aki | 8 CHEM113 – LECTURE Starch - a storage form for monosaccharides and is used as an energy source in cells - glucose is the monomeric unit a) - storage is the monomeric unit - two types of polysaccharides isolated from starch: Amylose: straight chain polymer – 15 -20% of the starch and has α (14) glycosidic bonds Molecular mass: 50,000 (up to 1000 glucose units) Amylopectin - Branched chain polymer – 80 – 85% of the starch α(14) glycosidic bond for straight chain and a (16) for branch - Molecular mass: 300,000 (up to 100,000 glucose units) – b) higher than amylose - Human can hydrolyze alpha linkage but not beta linkage Iodine is often used for the presence of starch in solution Starch-containing solutions turn a dark blue-black when iodine is added As starch is broken down through acid or enzymatic hydrolysis to glucose monomers, the blue-black color disappears Structural Polysaccharides Cellulose - Linear homopolysaccharide with β(1→4) glycosidic bond - Up to 5000 glucose units with molecular mass of 900,000 amu - Cotton is approximately 95% cellulose and wood are approximately 50 cellulose that hydrolyzes β (1→4) linkage so humans cannot digest cellulose - Some animals have bacteria that produces cellulase in their guts in order for them to get free glucose from cellulose - In humans, it serves as dietary fiber in food – readily absorbs water and results in softer stools and regular bowel movement - 23-35 g of dietary fiber is required everyday Chitin - Similar to cellulose in both function and structure - Linear polymer with all β(1→4)glycosidic linkages – it has a N-acetyl amino derivative of glucose - Function is to give rigidity to the exoskeleton s of crabs, lobsters, shrimp, insects and other arthropods LIPIDS biological molecules that are insoluble in water but soluble in nonpolar solvents. - have a wider spectrum of compositions and structures because they are defined in terms of their physical properties (water solubility). - the waxy, greasy, or oily compounds found in plants and animals. - wax coating that protects plants - used as energy storage - structural components (cell membranes) - insulation against cold Five Categories of Lipids: Energy-storage lipids - triacylglycerols Membrane lipids - phospholipids, sphingoglycolipids, and cholesterol Emulsification lipids - bile acids Chemical messenger lipids - steroid hormones and eicosanoids) Protective-coating lipids - biological waxes Saponifiable lipids - contain esters, which can undergo saponification (hydrolysis under basic conditions) (waxes, triglycerides, phosphoglycerides, sphingolipids) Simple lipids - contain two types of components (a fatty acid and an alcohol) Complex lipids - contain more than two components (fatty acids, an alcohol, and other components) Nonsaponifiable lipids - do not contain ester groups, and cannot be saponified (steroids, prostaglandins) - Fatty Acids long chain carboxylic acids - Properties of Fatty acids: The long, nonpolar hydrocarbon tails of fatty acids are responsible for most of the fatty or oily characteristics of lipids. The carboxyl (COOH) group is hydrophilic under basic conditions, such as physiological pH (7.4): Aki | 9 CHEM113 – LECTURE Micelles - In aqueous solutions, fatty acids associate with each other in spherical clusters - which the hydrocarbon tails tangle each other up through dispersion forces, leaving a “shell” of polar carboxylate ions facing outwards, in contact with the water. - Micelles are important in the transport of insoluble lipids in the blood, and in the actions of soaps. Characteristics of Fatty Acids: They are usually having straight chains (no branches) that are about 10 to 20 carbon atoms in length. They usually have an even number of carbon atoms (counting the carboxyl carbon). The carbon chains may be saturated (all single bonds) or unsaturated (containing double bonds). Other than the carboxyl group and the double bonds, there are usually no other functional groups. Shorter fatty acids usually have lower melting points than longer ones (stearic acid [18C] = 700C, palmitic acid [16C] = 630C). The double bonds are usually in cis configurations: Essential Fatty Acids: - Fatty acids that must be obtained from dietary sources – are not synthesized within the body - Two most important essential fatty acids are: Linoleic acid (18:2) - omega 6 Linolenic acid (18:3) - omega 3 - Both are needed for: Proper membrane structure Serve as starting materials for the production of several nutritionally important longer-chain omega-6 and omega-3 fatty acids - In the body, they are used to produce hormonelike substances that regulate blood pressure, blood clotting, blood lipid levels, the immune response, and inflammatory reactions. Types of Fatty Acids Saturated vs Unsaturated fatty acid - The cis-double bonds in unsaturated fatty acids put an inflexible “kink” in the carbon chain, preventing the molecules from packing together as tightly as saturated fatty acids do. - For example, stearic acid (saturated), oleic acid (one double bond), and linoleic acid (two double bonds) all have 18 carbons in the chain, but their melting points are drastically different: - Carboxylic acids with linear (unbranched) carbon chain Fatty acids are naturally occuring monocarboxylic acids - Even number of Carbon atoms: o Long chain fatty acids: C12 - C26 o Medium chain fatty acids: C6 - C11 o Short-chain fatty acids: C4 - C5 - Two Types: o Saturated - all C-C bonds are single bonds o Unsaturated o Monounsaturated: one C=C bond o Polyunsaturated: 2 or more C=C bonds present - up to six double bonds are present in fatty acids Saturated Fatty Acids – Numbering starts from the end of -COOH group – See structural notation: it indicates number of C atoms – Example - Lauric acid has 12 C atoms and no double bonds so it is (12:0) Unsaturated Fatty Acids – A monounsaturated fatty acid is a fatty acid with a carbon chain in which one carbon–carbon double bond is present. – Different ways of depicting the structure – Selected Unsaturated Fatty Acids of Biological Importance Numbering starts from the other end of COOH See structural notation: it indicates number of C atoms E.g., 18:2 – 18 carbons, 2 double bonds Polyunsaturated Fatty Acid (PUFAs) - a fatty acid with a carbon chain in which two or more carbon–carbon double bonds are present. – Up to six double bonds are found in biochemically important PUFAs. – Two types of unsaturated fatty acids. • Omega (ω)-3 fatty acids - An unsaturated fatty acid with its endmost double bond three carbon atoms away from its methyl end. • Omega(ω)-6 fatty acid is an unsaturated fatty acid with its endmost double bond six carbon atoms away from its methyl end. Omega Acids – Essential Fatty Acids: Must be part of diet – Nutritionally important Omega-3 and Omega-6 fatty acids Linolenic acid – Omega-3 Linoleic acid – Omega-6 – Linoleic Acid Deficiency: Skin redness - becomes irritated Infections and dehydration Liver abnormalities Children need it the most Human milk has more than cow’s milk A k i | 10 CHEM113 – LECTURE American Diet – Sufficient in omega 6 fatty acids – Deficient in omega 3 fatty acids Fish - good source for omega 3 fatty acids – High rate of heart disease may be due to imbalance in omega 3 and 6 fatty acids Ideal ratio: Omega 6: Omega 3 (4 - 10 g: 1g) Physical Properties of Fatty Acids Water solubility: Short chain fatty acids have some solubility whereas long chain fatty acids are insoluble Short chain fatty acids are sparingly soluble because of carboxylic acid polar group – Physical properties such as melting point depends on the number of C atoms and degree unsaturation The Melting Point – Melting Point Depends Upon: Length of carbon chain Degree of unsaturation (number of double bonds in a molecule) Space Filling Molecules - The number of bends in a fatty acid chain increase as the number of double bonds increase Less packing occurs Melting point is lower Tend to be liquids at room temperature Energy- Storage Lipids: Triacylglycerol’s - With the notable exception of nerve cells, human cells store small amounts of energy providing materials: The most widespread energy storage material carbohydrate glycogen Present in small amounts - Storage material is the triacylglycerols: Triacylglycerols are concentrated primarily in special cells (adipocytes) Nearly filled with the material. Two Types of Triacylglycerols: 1) Simple Triacylglycerols: Three identical fatty acids are esterified Naturally occurring simple triacylglycerols are rare 2) Mixed Triacylglycerols: A triester formed from the esterification of glycerol with more than one kind of fatty acid In nature mostly mixed triacylglycerols are found and are different even from the same source depending on the feed, e.g., corn, peanut and wheat -fed cows have different triacylglycerols Oils are triglycerides that are liquids at room temp. - usually derived from plants or fish - mostly unsaturated fatty acids – Fats and Oils Animal fats and vegetable oils are esters composed of three molecules of a fatty acid connected to a glycerol molecule, producing a structure called a triglyceride or triacylglycerol The fatty acids in a triglyceride molecule are usually not all the same natural triglycerides are often mixtures of many different triglyceride molecules. Fats are triglycerides that are solids at room temp. - usually derived from animals - mostly saturated fatty acids - Chemical Properties of Fats and Oils: Triglycerides can be broken apart with water and an acid catalyst (hydrolysis), or by digestive enzymes called lipases “Good Fats” Versus “Bad Fats” Current recommended amounts are: total fat intake in calories: 15% - Monounsaturated fat 10% - Polyunsaturated <10% - Saturated fats Saturated fats are considered “bad fats” Monounsaturated fats are considered “good fats” Trans-monounsaturated fats are considered “bad fats” Polyunsaturated fats can be both “good fats” and “bad fats” Omega 3 and 6 are important “good fats” Fat and Fatty Acid Composition of Nuts - Numerous studies now indicate that eating nuts can have a strong protective effect against coronary heart disease: Low amounts of saturated fatty acids Nuts also contain valuable antioxidant vitamins, minerals, and plant fiber protein Chemical Reactions of Triacylglycerols Partial Hydrolysis - Chemical Properties due to two functional groups: esters and alkenes Hydrolysis: Partial hydrolysis of triacylglycerols Breaking of 1-2 ester bonds to give rise to mono- or diacylglycerol and fatty acid(s) Carried out by enzymes produced by the pancreas Saponification - Triglycerides react with strong bases (NaOH or KOH) to form the carboxylate salts of the fatty acids called soaps - Hydrolysis in basic solution: Produce salt of fatty acid and glycerol - RCOOR’ + NaOH RCOONa (soap) + R’OH Soaps - NaOH produces a “hard” soap, commonly found in bar soaps; KOH produces a “soft” soap, such as those in shaving creams and liquid soaps. - These salts combine two solubility characteristics: 1) a long, nonpolar, water-insoluble (hydrophobic) hydrocarbon “tail.” 2) charged, water-soluble (hydrophilic) “head.” A k i | 11 CHEM113 – LECTURE - In water, the “tails” become tangled, leaving the charged heads sticking out into the solution, forming a structure called a micelle. Hydrogenation - alkenes are converted into alkanes with hydrogen gas (H2) and a catalyst (Pt, Ni, or some other metal). used to convert unsaturated vegetable oils, which are liquids at room temp., to saturated fats, which are solids at room temp. (shortening, etc.). In partially hydrogenated vegetable oils, not all of the double bonds are saturated, allowing the texture of the product to be controlled. In the process, this twists some of the naturallyoccurring cis double bonds into trans isomers (trans fats). Addition of hydrogen across double (=) bond increases degree of saturation Many food products are produced by partial hydrogenation of oils and fats Peanut oil + H2 Peanut Butter Vegetable oil + H2 Margerine - O O H 2C O C H2C O C O + 2H2 HC O C O O HC O C O H 2C O C H2C O C Oil Solid Oxidation - Double bonds in triacylglycerols are subject to oxidation with oxygen in air (an oxidizing agent)Leads to C=C breakage - oxidation of alkenes may result into two short chain molecules – an aldehyde or a carboxylic acid: - The aldehydes and/or carboxylic acids so produced often have objectionable odors - fats and oils are said to be rancid - To avoid this unwanted oxidation process antioxidants are added as preservatives, e.g., Vitamin C and vitamin E are good antioxidant preservatives. - Waxes simple lipids contain a fatty acid joined to a long-chain (1232 carbons) alcohol insoluble in water, and not as easily hydrolyzed as fats and oils. They often occur in nature as protective coatings on feathers, fur, skin, leaves, and fruits. Sebum, secreted by the sebaceous glands of the skin, contains waxes that help to keep skin soft and prevent dehydration. - used commercially to make cosmetics, candles, ointments, and protective polishes. Membrane Lipids: Phospholipids All cells are surrounded by a membrane that confines their contents. – Up to 80% of the mass of a cell membrane can be lipid materials and these lipid materials are dominated by phospholipids. – A phospholipid contains one or more fatty acids, a phosphate group, a platform molecule (glycerol or sphingosine) to which the fatty acid(s) and the phosphate group are attached, and an alcohol that is attached to the phosphate group. Glycerophospholipids – a lipid that contains two fatty acids and a phosphate group esterified to a glycerol molecule and an alcohol esterified to the phosphate group. – All attachments (bonds) between groups in a glycerophospholipid are ester linkages – have four ester linkages as contrasted to three ester linkages in triacylglycerols. – undergo hydrolysis and saponification reactions in a manner similar to that for triacylglycerols – The alcohol attached to the phosphate group in a glycophospholipid is usually one of three amino alcohols: choline, ethanolamine, or serine - respectively known as phosphatidylcholines, phosphatidylethanolamines, and phosphatidylserines. – Structurally glycerophospholipids are alghough similar to triacylglycerols, they have different biochemical functions. Triacylglycerols serve as energy storage molecules Glycerophospholipids function as components of cell membranes - A major structural difference between the two types of lipids is that of their “polarity” – Responsible for their differing biochemical functions. Triacylglycerols are a non-polar Glycerophospholipids are polar. Sphingophospholipids – Structures based on the 18-carbon monounsaturated aminodialcohol sphingosine – contains one fatty acid and one phosphate group attached to a sphingosine molecule and an alcohol attached to the phosphate group – A k i | 12 CHEM113 – LECTURE Saponifiable lipids – which the alcohol esterified to the phosphate group is choline are called sphingomyelins. Sphingomyelins – are found in all cell membranes and are important structural components of the myelin sheath of neurons Sphingoglycolipids: Contains both a fatty acid and carbohydrate Simple sphingoglycolipids are called cerebrosides: contains a single monosaccharide unit - either glucose or galactose – They occur primarily in brain (7% of dry mass) Cholesterol in Food: Liver synthesizes cholesterol: ~ 1g everyday; so it is not necessary to consume in the form of diet Cholesterol synthesis decrease if it is ingested but reduction is not sufficient: Leads to cardiovascular disease Animal Food: Lot of cholesterol Plant Food: No cholesterol Phosphoglycerides complex lipids that are major components of cell membranes. - Phosphoglycerides and related compounds are also called phospholipids. Amino alcohols in Phosphoglycerides - The most abundant phosphoglycerides contain the alcohols choline, ethanolamine, or serine attached to the phosphate group Lecithin - Phosphoglycerides that contains the aminoalcohol choline - The fatty acids at the first and second positions are variable, so there are a number of different possible lecithins. - Because lecithin’s contain negatively charged oxygen atoms in the phosphate group and positively charged nitrogen atoms in the quaternary ammonium salt group, that end of the molecule is highly hydrophilic, while the rest of the molecule is hydrophobic. This allows lecithin to act as an emulsifying agent: - forms an important structural component of cell membranes. - forms micelles which play a role in the transport of lipids in the blood stream. - Commercially, lecithin extracted from soybeans is used as an emulsifying agent in margarine and candies to provide a smooth texture. - Gangliosides - Complex sphingoglycolipids - contain a branched chain of up to seven monosaccharide residues. - Occur in the gray matter of the brain as well as in the myelin sheath. Membrane Lipids: Cholesterol the most abundant steroid in the body. It is an essential component of cell membranes, and is a precursor for other steroids, such as the bile salts, sex hormones, vitamin D, and the adrenocorticoid hormones. - There is apparently a correlation between high levels of cholesterol in the blood and atherosclerosis. Cholesterol-Third major type of membrane lipid: - Lipids: Fused Rings - Cholesterol: C27 steroid molecule - A steroid is a lipid whose structure is based on a fused ring system of three 6 carbon rings and one 5 carbon ring. - Important in human cell membranes, nerve tissue and brain tissue - Important in chemical synthesis: Hormones, vitamins essential for life - Cephalins - Phosphoglycerides that contains the aminoalcohols ethanolamine or serine - found in most cell membranes, and are particularly abundant in brain tissue. They are also found in blood platelets, and play a role in blood clotting. - Sphingolipids complex lipids that contain sphingosine instead of glycerol. A k i | 13 CHEM113 – LECTURE Sphingomyelins - have sphingosine or a related dihydroxyamine as their backbone - abundant in brain and nerve tissue - major constituent of the coating around nerve fibers Glycolipids - sphingolipids that contain carbohydrates (usually monosaccharides). - They are also referred to as cerebrosides because of their abundance in brain tissue. - - Fats are no longer digested properly, and bile pigments absorbed into the blood causes the skin to become yellow and the stool to become gray. Prostaglandins cyclic compounds synthesized from arachidonic acid. Like hormones, they are involved in a host of body processes, including reproduction, blood clotting, inflammation, and fever. (Aspirin works by inhibiting prostaglandin production, alleviating inflammation and fever. NSAIDs has the similar mechanism) Emulsification Lipids: Bile Acids An emulsifier is a substance that can disperse and stabilize water-insoluble substances as colloidal particles in an aqueous solution. – Bile Acids: Cholesterol derivatives that functions as emulsifying agents that make dietary lipids soluble in aqueous environment of the digestive tract: Approximately one third of cholesterol produced by liver is converted to bile acids. Action similar to soap in washing Bile Acids – tri- or dihydroxy cholesterol derivatives – The carbon 17 side chain of cholesterol has been oxidized to a carboxylic acid – The oxidized acid side chain is bonded to an amino acid (either glycine or taurine) through an amide linkage – Bile is a fluid containing emulsifying agents (Bile acids) secreted by the liver, stored in the gallbladder, and released into the small intestine during digestion – Biological Membranes Most cell membranes contain about 60% lipids and 40% proteins: phosphoglycerides (e.g., lecithin and cephalin) sphingomyelin cholesterol - The fluid-mosaic model of the cell pictures the cell membrane as being composed of a lipid bilayer, in which the nonpolar tails of lipids point towards the “interior” of the Messenger Lipids: Steroid Hormones bilayer, leaving the polar, hydrophilic portions pointing - A hormone is a biochemical substance produced by a outwards. ductless gland that has a messenger function. - When the membrane is broken, the repulsion between the nonpolar portion and water causes the membrane to re-form. - Hormones serve as a means of communication between various tissues. Cell membranes also contain unsaturated fatty acid Some hormones are lipids. chains that increase the flexibility or fluidity of the The lipids that play the role of “chemical messengers” membrane. include: Some of the proteins in the membrane “float” in the Steroid hormones – derivatives of cholesterol lipid bilayer like icebergs, while others extend through Eicosanoids- derivatives of arachidonic acid the bilayer. - There are two major classes of steroid hormones: The lipid molecules are free to move laterally within Sex hormones - control reproduction and secondary the bilayer like dancers on a crowded dance floor. Fluid Mosaic Model sex characteristics - lipids of the bilayer are in constant motion, gliding from one Adrenocorticoid hormones – control numerous part of their bilayer to another at high speed biochemical processes in the body Bile Salts Steroids - yellowish brown or green fluid produced in the liver and - classified as lipids because they are soluble in nonpolar stored in the gall bladder. solvents, but they are nonsaponifiable because the - act like soaps and other emulsifiers: they contain both polar components are not held together by ester linkages. and nonpolar regions, helping to break fats in foods into - The basic steroid structure contains four fused rings smaller pieces, allowing them to be hydrolyzed more easily. Sex hormones Gallstones - produced in the testes and ovaries regulate the production of - Bile salts also emulsify cholesterol in the bile, so it can be sperm and eggs and aid in the development of secondary sex removed in the small intestine. characteristics. - If cholesterol levels are too high or the levels of bile salts is - Classified into three major groups: too low, the cholesterol precipitates and forms gallstones. Estrogens - the female sex hormones - Gallstones can block the duct that allows bile to be secreted Androgens - the male sex hormones into the duodenum. Progestins - the pregnancy hormones - A k i | 14 CHEM113 – LECTURE Adrenocorticoid hormones - Hormones are chemicals released by cells or glands in one part of the body that send out messages that affect cells in other parts of the body. Many hormones are based on steroids. - 28 Different hormones have been isolated from the adrenal cortex - are produced in the adrenal glands (located on the top of the kidney). - Two types of adrenocorticoid hormones: Glucocorticoids - control glucose metabolism and counteract inflammation - such as cortisol affect the metabolism of carbohydrates. - Cortisol and its derivatives, cortisone and prednisolone (synthetic) are powerful antiinflammatory drugs used to treat arthritis and asthma. Mineralocorticoids - control the balance of Na and K ions in cells - regulate ion concentration (mainly Na+). - Aldosterone influces the absorption of Na+ and Clin kidney tubules, thus regulating the retention of water in the body Messenger Lipids: Eicosanoids Eicosanoids Arachidonic acid (20:4) derivatives: Have profound physiological effects at extremely low concentrations. Eicosanoids are hormone-like molecules Exert their effects in the tissues where they are synthesized. Eicosanoids usually have a very short “life.” Physiological effects of eicosanoids: Inflammatory response Production of pain and fever Regulation of blood pressure Induction of blood clotting Control of reproductive functions, such as induction of labor Regulation of the sleep/wake cycle Three Types 1. Prostoglandins: - C20-fatty-acid derivative containing cyclopentane ring and oxygen-containing functional groups - Involved in raising body temperature, - Inhibiting the secretion of gastric juices, - Increasing the secretion of a protective mucus layer into the stomach, - Relaxing and contracting smooth muscle, directing water and electrolyte balance, intensifying pain, and enhancing inflammation responses. 2. Thromboxanes: - C20-fatty-acid derivative containing a cyclic ether ring and oxygen-containing functional groups - Promote platelet aggregation. 3. Leukotrienes: - C20-fatty-acid derivative containing three conjugated double bonds and hydroxy groups - Promote inflammatory and hypersensitivity (allergy) responses Protective- Coating Lipids: Biological Waxes A biological wax: a monoester of a long-chain fatty acid and a long-chain alcohol. – The fatty acids found in biological waxes: Generally are saturated fatty acids Contain 14 to 36 carbon atoms. – The alcohols found in biological waxes: May be saturated or unsaturated May contain 16 to 30 carbon atoms. Properties of Biological waxes: - Water-insoluble and water-repellent because of long nonpolar hydrocarbon chains. - Humans and animals secrete biological waxes from skin glands Function of biological waxes: – Protect hair and skin; and keep it pliable and lubricated. – Impart water repellency to animal fur. – Birds keep their feathers water repellent and help minimize loss of body heat – Plants coat their leaves with a thin layer of biological waxes to prevent excessive evaporation of water and to protect against parasite attack. – - - - - - PROTEINS Greek proteios, “primary” or “of first importance” biochemical molecules consisting of polypeptides joined by peptide bonds between the amino and carboxyl groups of amino acid residues. Proteins perform a number of vital functions: Enzymes are proteins that act as biochemical catalysts. Many proteins have structural or mechanical functions (e.g., actin and myosin in muscles). Proteins are important in cell signaling, immune responses, cell adhesion, and the cell cycle. Proteins are a necessary component in animal diets. All proteins are polymers containing chains of amino acids chemically bound by amide (peptide) bonds. Most organisms use 20 naturally-occurring amino acids to build proteins. The linear sequence of the amino acids in a protein is dictated by the sequence of the nucleotides in an organisms’ genetic code. These amino acids are called alpha (a)-amino acids because the amino group is attached to the first carbon in the chain connected to the carboxyl carbon. Amino Acids classified by the polarity of the R group side chains, and whether they are acidic or basic: neutral, nonpolar neutral, polar basic, polar (contains an additional amino group) acidic, polar (contains an additional carboxylate group) All of the amino acids are also known by a three letter and one-letter abbreviations. Since the amino acids (except for glycine) contain four different groups connected to the a-carbon, they are chiral, and exist in two enantiomeric forms: A k i | 15 CHEM113 – LECTURE - - The amino acids in living systems exist primarily in the L form. Because amino acids contain both an acidic and a basic functional group, an internal acid-base reaction occurs, forming an ion with both a positive and a negative charge called a zwitterion: - - - In solution, the structure of an amino acid can change with the pH of the solution In solution, the structure of an amino acid can change with the pH of the solution. Amino acids: Zwitterions Lowering the pH of the solution causes the zwitterion to pick up a proton: - - Increasing the pH of the solution causes the zwitterion to lose a proton: - - Since the pH of the solution affects the charge on the amino acid, at some pH, the amino acid will form a zwitterion. This is called the isoelectric point. Each amino acid (and protein) has a characteristic isoelectric point: those with neutral R groups are near a pH of 6, those with basic R groups have higher values, and those with acidic R groups have lower values. Because amino acids can react with both H3O+ and OH-, solutions of amino acids and proteins can act as buffers. (E.g., blood proteins help to regulate the pH of blood.) Reaction of Amino acids: Oxidation Amino acids can undergo any of the reaction’s characteristic of the functional groups in the structure. Cysteine is the only amino acid that contains a sulfhydryl (thiol, R—SH) group. Thiols are easily oxidized to form disulfide bonds (R—S—S—R). This allows cysteine to dimerize to form cystine Peptide formation Amides can be thought of as forming from the reaction of an amine and a carboxylic acid: In the same way, two amino acids can combine to form a dipeptide, held together by a peptide bond: Peptides Short chains are referred to as peptides, chains of up to about 50 amino acids are polypeptides, and chains of more than 50 amino acids are proteins. (The terms protein and polypeptide are often used interchangeably.) Amino acids in peptide chains are called amino acid residues. The residue with a free amino group is called the Nterminal residue, and is written on the left end of the chain. The residue with a free carboxylate group is called the C-terminal residue, and is written on the right end of the chain. Peptides are named by starting at the N-terminal end and listing the amino acid residues from left to right. Large amino acid chains are unwieldy to draw in their complete forms, so they are usually represented by their three-letter abbreviations, separated by dashes: Gly-Ala (Gly = N-terminal, Ala = C-terminal) Ala-Gly (Ala = N-terminal, Gly = C-terminal) The tripeptide alanylglycylvaline can be written as Ala-GlyVal. (There are five other arrangements of these amino acids that are possible.) Insulin has 51 amino acids, with 1.55x1066 different possible arrangements, but the body produces only one. Oxytocin and Vasopressin More than 200 peptides have been identified as being essential to the body’s proper functioning. Vasopressin and oxytocin are nonapeptide hormones secreted by the pituitary gland. Six of the amino acid residues are held in a loop by disulfide bridges formed by the oxidation of two cysteine residues. Even though the molecules are very similar, their biological functions are quite different: Vassopressin is known as antidiuretic hormone (ADH) because it reduces the amount of urine formed, which causes the body to conserve water. It also raises blood pressure. Oxytocin causes the smooth muscles of the uterus to contract, and is administered to induce labor. It also stimulates the smooth muscles of mammary glands to stimulate milk ejection. A k i | 16 CHEM113 – LECTURE - - - - 1. Adrenocorticotropic hormone 39-residue peptide produced in the pituitary gland. It regulates the production of steroid hormones in the cortex of the adrenal gland. Characteristics of Proteins: Size Proteins are very large polymers of amino acids with molecular weights that vary from 6000 amu to several million amu. Glucose (C6H12O6 ) = 180 amu Hemoglobin (C2952H4664O832N812S8Fe4) = 65,000 amu Proteins are too large to pass through cell membranes, and are contained within the cells where they were formed unless the cell is damaged by disease or trauma. Persistent large amounts of protein in the urine are indicative of damaged kidney cells. Heart attacks can also be confirmed by the presence of certain proteins in the blood that are normally confined to cells in heart tissue. Acid Base Properties of Proteins Proteins take the form of zwitterions. They have characteristic isoelectric points, and can behave as buffers in solutions. The tendency for large molecules to remain in solution or form stable colloidal dispersions depends on the repulsive forces acting between molecules with like charges on their surfaces. When proteins are at a pH in which there is a net positive or negative charge, the like charges cause the molecules to repel one another, and they remain dispersed. When the pH is near the isoelectric point, the net charge on the molecule is zero, and the repulsion between proteins is small. This causes the protein molecules to clump and precipitate from solution. Protein Function Proteins perform crucial roles in all biological processes. Catalytic function: Nearly all reactions in living organisms are catalyzed by proteins functioning as enzymes. Without these catalysts, biological reactions would proceed much more slowly. 2. Structural function: In animals structural materials other than inorganic components of the skeleton are proteins, such as collagen (mechanical strength of skin and bone) and keratin (hair, skin, fingernails). 3. Storage function: Some proteins provide a way to store small molecules or ions, e.g., ovalbumin (used by embryos developing in bird eggs), casein (a milk protein) and gliadin (wheat seeds), and ferritin (a liver protein which complexes with iron ions). 4. Protective function: Antibodies are proteins that protect the body from disease by combining with and destroying viruses, bacteria, and other foreign substances. Another protective function is blood clotting, carried out by thrombin and fibrinogen. 5. Regulatory function: Body processes regulated by proteins include growth (growth hormone) and thyroid functions (thyrotropin). 6. Nerve impulse transmission: Some proteins act as receptors for small molecules that transmit impulses across the synapses that separate nerve cells (e.g., rhodopsin in vision). 7. Movement function: The proteins actin and myosin are important in muscle activity, regulating the contraction of muscle fibers. 8. Transport function: Some proteins bind small molecules or ions and transport them through the body. Serum albumin is a blood protein that carries fatty acids between fat (adipose) tissue and other organs. Hemoglobin carries oxygen from the lungs to other body tissues. Transferrin is a carrier of iron in blood plasma. A typical human cell contains 9000 different proteins; the human body contains about 100,000 different proteins. Protein Classes by Structure - Proteins can be classified on the basis of their structural shapes: - Fibrous proteins are made up of long rod-shaped or stringlike molecules that can intertwine with one another and form strong fibers. insoluble in water major components of connective tissue, elastic tissue, hair, and skin e.g., collagen, elastin, and keratin. - Globular proteins are more spherical in shape dissolve in water or form stable suspensions. not found in structural tissue but are transport proteins, or proteins that may be moved easily through the body by the circulatory system e.g., hemoglobin and transferrin. Protein Classes by Composition Proteins can also be classified by composition: Simple proteins contain only amino acid residues. Conjugated proteins also contain other organic or inorganic components, called prosthetic groups. a) nucleoproteins — nucleic acids (viruses). b) lipoproteins — lipids (fibrin in blood, serum lipoproteins) c) glycoproteins — carbohydrates (gamma globulin in blood, mucin in saliva) A k i | 17 CHEM113 – LECTURE d) phosphoproteins — phosphate groups (casein in milk) e) hemoproteins — heme (hemoglobin, myoglobin, cytochromes) f) metalloproteins — iron (feritin, hemoglobin) or zinc (alcohol dehydrogenase) Protein Structure - The structure of proteins is much more complex than that of simple organic molecules. - Many protein molecules consist of a chain of amino acids twisted and folded into a complex three-dimensional structure - The complex 3D structures of proteins impart unique features to proteins that allow them to function in diverse ways. - There are four levels of organization in proteins structure: primary, secondary, tertiary, and quaternary. Primary structure - The linear sequence of the side chains that are connected to the protein backbone - Each protein has a unique sequence of amino acid residues that cause it to fold into a distinctive shape that allows the protein to function properly Secondary Structure - Hydrogen bonding causes protein chains to fold and align to produce orderly patterns called secondary structures. The a-Helix - a single protein chain twisted to resemble a coiled helical spring. - held in this shape by hydrogen bonding interactions between amide groups, with the side chains extending outward from the coil. - The amount of a-helix coiling in proteins is highly variable. - In a-keratin (hair, pictured below), myosin (muscles), epidermin (skin), and fibrin (blood clots), two or more helices coil together (supracoiling) to form cables. The b-Pleated Sheet - Another secondary structure is the b-pleated sheet, in which several protein chains lie side by side, held by hydrogen bonds between adjacent chains less common than the ahelix; - it is found extensively only in the protein of silk. - The figure below shows both types of secondary structures in a single protein. Tertiary Structure - refers to the bending and folding of the protein into a specific three-dimensional shape. - These structures result from four types of interactions between the R side chains of the amino acids residues: 1. Disulfide bridges can form between two cysteine residues that are close to each other in the same chain, or between cysteine residues in different chains. These bridges hold the protein chain in a loop or some other 3D shape. 2. Salt bridges are attractions between ions that result from the interactions of the ionized side chains of acidic amino acids (—COO-) and the side chains of basic amino acids (—NH3 +). 3. Hydrogen bonds can form between a variety of side chains, especially those that contain: Hydrogen bonding also influences the secondary structure, but here the hydrogen bonding is between R groups, while in secondary structures it is between the C=O and NH portions of the backbone. 4. Hydrophobic interactions result from the attraction of nonpolar groups, or when they are forced together by their mutual repulsion of the aqueous solvent. These interactions are particularly important between the benzene rings in phenylalanine or tryptophan. This type of interaction is relatively weak, but since it acts over large surface areas, the net effect is a strong interaction. - The compact structure of globular proteins in aqueous solution, in which the nonpolar groups are pointed inward, away from the water molecules. Quaternary Structure - When two or more polypeptide chains are held together by disulfide bridges, salt bridges, hydrogen bond, or hydrophobic interactions, forming a larger protein complex. - Each of the polypeptide subunits has its own primary, secondary, and tertiary structure. - The arrangement of the subunits to form a larger protein is the quaternary structure of the protein. Hemoglobin - made of four subunits: two identical alpha chains containing 141 AA’s and two identical beta chains containing 146 AA’s. - Each subunit contains a heme group located in crevices near the exterior of the molecule. - A hemoglobin molecule in a person suffering from sicklecell anemia has a one-amino acid difference in the sixth position of the two b-chains of normal HbA (a glutamate is replaced with a valine). - This changes the shape of red blood cells that carry this mutation to a characteristic sickle shape, which causes the cells to clump together and wedge in capillaries, particularly in the spleen, and cause excruciating pain. - Cells blocking capillaries are rapidly destroyed, and the loss of these red blood cells causes anemia. Protein Hydrolysis - Amides can be hydrolyzed under acidic or basic conditions. - The peptide bonds in proteins can be broken down under acidic or basic conditions into smaller peptides, or all the way to amino acids, depending on the hydrolysis time, temperature, and pH - The digestion of proteins involves hydrolysis reactions catalyzed by digestive enzymes. - Cellular proteins are constantly being broken down as the body resynthesizes molecules and tissues that it needs. Protein Denaturation - Proteins are maintained in their native state (their natural 3D conformation) by stable secondary and tertiary structures, and by aggregation of subunits into quaternary structures. - Denaturation is caused when the folded native structures break down because of extreme temps. or pH values, which disrupt the stabilizing structures. The structure becomes random and disorganized. - Most proteins are biologically active only over a temperature range of 00C to 400C. - Heat is often used to kill microorganisms and deactivate their toxins. The protein toxin from Clostridium botulinum A k i | 18 CHEM113 – LECTURE - - is inactivated by being heated to 1000C for a few minutes; heating also deactivates the toxins that cause diphtheria and tetanus. Heat denaturation is used to prepare vaccines against some diseases. The denatured toxin can no longer cause the disease, but it can stimulate the body to produce substances that induce immunity. Proteins can also be denatured by heavy-metal ions such as Hg2+, Ag+, and Pb2+ that interact with —SH and carboxylate groups. - Organic materials containing Hg (mercurochrome and merthiolate) were common topical antiseptics. - Heavy-metal poisoning is often treated with large doses of raw egg white and milk; the proteins in the egg and milk bind to the metal ions, forming a precipitate, which is either vomited out or pumped out. Wala akong maintindihan sa subject na to kaya copy paste lahat yan galing sa ppt ni Sir Jess HAHAHA ung mga ppt na ginamit ko… Cell – Sir Magno Carbohydrates – Sir Magno Lipids – Sir Magno and Mam Merly Proteins – Sir Magno Ung sa lipids, pinagsama ko na un ppt ni mam merly at sir jess. Pero sa proteins, balak ko sana ipagsama na rin kaso nga lang, hindi ko alam kung paano ko isisingit un ppt ni mam merly. Kaya hiniwalay ko nlng ung kay sir tas un kay mam merly nasa next page (page 20). Nahirapan nga din ako isingit un ppt ni mam sa lipids eee kaya mukhang marami at magulo. May docx din ako nito, nasa drive lang nakafolder! Kung may Nakita kayong mali or nahahabaan kayo sa reviewer na to, download nyo lng un docx na yon then edit nyo nlnggg hihi https://drive.google.com/drive/folders/1GFXdK8QI2s03Ot19DbkQoxN9MGGhJLPI?usp=sharing Andito ung mga ppt ni sir: (andiyan din un ppt ni mam merly) https://drive.google.com/drive/folders/13WIAlmrk58a4f20idZUuCxdHhT3uo2ci?usp=sharing About sa CHEM Laboratory: D ako gumawa ng reviewer sa biochem lab, kasii depende daw sa prof nyo yon, kung ano ung ipapaexam sainyo. Kami, kaila Sir Jess, hindi daw sya nagpapaexam ng lab sa prelim at midterm, sa finals na daw lahat. Kayaa ask nyo prof nyo kung paano ung exam nyo sa lab. Kayo na bahala kung paano nyo intindihin yan HAHAHA nilagay ko lang lahat sa isang word para maprint nyo sya. Good luck future RNs!! Papasa tayo sa biochem!! Whooo! pati sa lahat ng subj! RAWRRR Aki ~ ~ ~ A k i | 19 CHEM113 – LECTURE Characteristics of Protein A protein is a naturally-occurring, unbranched polymer in which the monomer units are amino acids Proteins are most abundant molecules in the cells after water – account for about 15% of a cell’s overall mass Elemental composition - Contain Carbon (C), Hydrogen (H), Nitrogen (N), Oxygen (O), most also contain Sulfur (S) The average nitrogen content of proteins is 15.4% by mass Also present are Iron (Fe), phosphorus (P) and some other metals in some specialized proteins Amino Acids: The building Blocks Amino acid - An organic compound that contains both an amino (-NH2) and carboxyl (-COOH) groups attached to same carbon atom The position of carbon atom is Alpha (a) -NH2 group is attached at alpha (a) carbon atom. -COOH group is attached at alpha (a) carbon atom. - R = side chain –vary in size, shape, charge, acidity, functional groups present, hydrogen-bonding ability, and chemical reactivity. >700 amino acids are known Based on common “R” groups, there are 20 standard amino acids - All amino acids differ from one another by their R-groups - Standard amino acids are divided into four groups based on the properties of R-groups - Non-polar amino acids: R-groups are non-polar Such amino acids are hydrophobic-water fearing (insoluble in water) 8 of the 20 standard amino acids are non polar When present in proteins, they are located in the interior of protein where there is no polarity Polar amino acids: R-groups are polar a) Polar-neutral: contains polar but neutral side chains Seven amino acids belong to this category b) Polar acidic: Contain carboxyl group as part of the side chains Two amino acids belong to this category c) Polar basic: Contain amino group as part of the side chain Two amino acids belong to this category Nomenclature - Common names assigned to the amino acids are currently used. - Three letter abbreviations - widely used for naming: First letter of amino acid name is compulsory and capitalized followed by next two letters not capitalized except in the case of Asparagine (Asn), Glutamine (Gln) and tryptophan (Trp). - One-letter symbols - commonly used for comparing amino acid sequences of proteins: Usually the first letter of the name When more than one amino acid has the same letter the most abundant amino acid gets the 1st letter. Non-Polar Amino Acids - Polar Neutral Amino Acids Polar Acidic and Basic Amino Acids A k i | 20 CHEM113 – LECTURE - - - Chirality and Amino Acids Four different groups are attached to the a-carbon atom in all of the standard amino acids except glycine In glycine R-group is hydrogen Therefore 19 of the 20 standard amino acids contain a chiral center Chiral centers exhibit enantiomerism (left- and right-handed forms) Each of the 19 amino acids exist in left and right-handed forms The amino acids found in nature as well as in proteins are L isomers. Bacteria do have some D-amino acids With monosaccharides nature favors D-isomers The rules for drawing Fischer projection formulas for amino acid structures The — COOH group is put at the top, the R group at the bottom to position the carbon chain vertically The — NH2 group is in a horizontal position. Positioning — NH2 on the left - L isomer Positioning — NH2 on the right - D isomer. Cysteine: A Chemically Unique Amino Acid Cysteine: the only standard amino acid with a sulfhydryl group (— SH group). - The sulfhydryl group imparts cysteine a chemical property unique among the standard amino acids. - Cysteine in the presence of mild oxidizing agents dimerizes to form a cystine molecule. Cystine - two cysteine residues linked via a covalent disulfide bond. Peptides - Under proper conditions, amino acids can bond together to produce an unbranched chain of amino acids. - The length of the amino acid chain can vary from a few amino acids to many amino acids. - Such a chain of covalently-linked amino acids is called a peptide. - The covalent bonds between amino acids in a peptide are called peptide bonds. - Dipeptide: bond between two amino acids Oligopeptide: bond between ~ 10 - 20 amino acids Polypeptide: bond between large number of amino acids Every peptide has an N-terminal end and a C-terminal end + H3N-aa-aa-aa-aa-aa-aa-aa-aa-aa-COOOH N-terminal end O +H 3N CH CH 3 - - Acid-base Properties of Amino acids In pure form amino acids are white crystalline solids Most amino acids decompose before they melt Not very soluble in water Exists as Zwitterion: An ion with + (positive) and – (Nagetive) charges on the same molecule with a net zero charge Carboxyl groups give-up a proton to get negative charge Amino groups accept a proton to become positive Amino acids in solution exist in three different species (zwitterions, positive ion, and negative ion) - Equilibrium shifts with change in pH Isoelectric point (pI) – pH at which the concentration of Zwitterion is maximum -- net charge is zero Different amino acids have different isoelectric points At isoelectric point - amino acids are not attracted towards an applied electric field because they net zero charge. COO- COOH +H N 3 C H CH3 Low pH (net + charge) + H3N C COO- H CH3 Zwitter Ion (net neutral charge) H2N C H CH3 High pH (net - charge) Alanine C O H N CH C CH2 Phenylalanine H N CH2 O CH C O- C-terminal end Serine Peptide Nomenclature - The C-terminal amino acid residue keeps its full amino acid name. - All of the other amino acid residues have names that end in -yl. The -yl suffi x replaces the -ine or -ic acid ending of the amino acid name, except for tryptophan, for which -yl is added to the name. - The amino acid naming sequence begins at the N-terminal amino acid residue. - Example: Ala-leu-gly has the IUPAC name of alanylleucylglycine Isomeric Peptides - Peptides that contain the same amino acids but present in different order are different molecules (constitutional isomers) with different properties For example, two different dipeptides can be formed between alanine and glycine - The number of isomeric peptides possible increases rapidly as the length of the peptide chain increases A k i | 21 CHEM113 – LECTURE Biochemically Important Small Peptides Many relatively small peptides are biochemically active: Hormones Neurotransmitters Antioxidants Small Peptide Hormones: Best-known peptide hormones: oxytocin and vasopressin Produced by the pituitary gland nonapeptide (nine amino acid residues) with six of the residues held in the form of a loop by a disulfide bond formed between two cysteine residues Small Peptide Neurotransmitters - Enkephalins are pentapeptide neurotransmitters produced by the brain and bind receptor within the brain - Help reduce pain - Best-known enkephalins: Met-enkephalin: Tyr–Gly–Gly–Phe–Met Leu-enkephalin: Tyr–Gly–Gly–Phe–Leu Small Peptide Antioxidants - Glutathione (Glu–Cys–Gly) – a tripeptide – is present is in high levels in most cells Regulator of oxidation–reduction reactions. - Glutathione is an antioxidant and protects cellular contents from oxidizing agents such as peroxides and superoxides Highly reactive forms of oxygen often generated within the cell in response to bacterial invasion - Unusual structural feature – Glu is bonded to Cys through the side-chain carboxyl group. Protein Classification Based on Chemical Composition - Simple proteins: A protein in which only amino acid residues are present: More than one protein subunit may be present but all subunits contain only amino acids - Conjugated protein: A protein that has one or more nonamino acid entities (prosthetic groups) present in its structure: One or more polypeptide chains may be present Non-amino acid components - may be organic or inorganic - prosthetic groups Lipoproteins contain lipid prosthetic groups Glycoproteins contain carbohydrate groups, Metalloproteins contain a specific metal as prosthetic group Four Types of Structures Primary Structure - refers to the order in which amino acids are linked together in a protein - Every protein has its own unique amino acid sequence Frederick Sanger (1953) sequenced and determined the primary structure for the first protein - Insulin Primary Structure of a Human Myoglobin: - - - General Structural Characteristics of Proteins General definition: A protein is a naturally-occurring, unbranched polymer in which the monomer units are amino acids. Specific definition: A protein is a peptide in which at least 40 amino acid residues are present: The terms polypeptide and protein are often used interchangeably used to describe a protein Several proteins with >10,000 amino acid residues are known Common proteins contain 400–500 amino acid residues Small proteins contain 40–100 amino acid residues More than one peptide chain may be present in a protein: Monomeric: A monomeric protein contains one peptide chain Multimeric: A multimeric protein contains more than one peptide chain - Proteins of the same organism always same sequence (cows, pigs, etc.) Different sources: Insulin from pigs, cows, sheep, humans similar Some differences: Species Human Pig (porcine) Cow (bovine) - Chain A AA #8 AA #9 Thr Thr Ser Ser AA #10 Ile Ile Ala Ser Val Chain B AA #30 Thr Ala Ala Due to differences insulin may show some reaction over time Now human insulin produced from genetically engineered bacteria A k i | 22 CHEM113 – LECTURE Secondary Structure of Proteins - Arrangement of atoms of backbone in space. - The two most common types: alpha-helix (a-helix) and the beta-pleated sheet (b-pleated sheet). - The peptide linkages are essentially planar thus allows only two possible arrangements for the peptide backbone for the following reasons: For two amino acids linked through a peptide bond six atoms lie in the same plane The planar peptide linkage structure has considerable rigidity, therefore rotation of groups about the C–N bond is hindered Cis–trans isomerism is possible about C–N bond. The trans isomer is the preferred orientation Alpha-helix (a-helix) - A single protein chain adopts a shape that resembles a coiled spring (helix): H-bonding between same amino acid chains –intra molecular Coiled helical spring R-group outside of the helix -- not enough room for them to stay inside Beta-Pleated Sheets - Completely extended amino acid chains - H-bonding between two different chains – inter and/or intramolecular - Side chains below or above the axis Tertiary Structure of Proteins - The overall three-dimensional shape of a protein - Results from the interactions between amino acid side chains (R groups) that are widely separated from each other. - In general, 4 types of interactions are observed. 1) Disulfide bond: covalent, strong, between two cysteine groups 2) Electrostatic interactions: Salt Bridge between charged side chains of acidic and basic amino acids -OH, -NH2, -COOH, -CONH2 3) H-Bonding between polar, acidic and/or basic R groups For H-bonding to occur, the H must be attached on O, N or F 4) Hydrophobic interactions: Between non-polar side chains Quaternary Structure of Proteins - refers to the organization among the various peptide chains in a multimeric protein: Highest level of protein organization Present only in proteins that have 2 or more polypeptide chains (subunits) Subunits are generally Independent of each other not covalently bonded Proteins with quartenary structure are often referred to as oligomeric proteins Contain even number of subunits Protein Classification Based on Shape Three types of proteins: fibrous, globular, and membrane Fibrous proteins: protein molecules with elongated shape: Generally insoluble in water Single type of secondary structure Tend to have simple, regular, linear structures Tend to aggregate together to form macromolecular structures, e.g., hair, nails, etc - Globular proteins: protein molecules with peptide chains folded into spherical or globular shapes: Generally, water soluble – hydrophobic amino acid residues in the protein core Function as enzymes and intracellular signaling molecules - Membrane proteins: associated with cell membranes Insoluble in water – hydrophobic amino acid residues on the surface Help in transport of molecules across the membrane Fibrous Proteins: Alpha-Keratin - Provide protective coating for organs - Major protein constituent of hair, feather, nails, horns and turtle shells - Mainly made of hydrophobic amino acid residues - Hardness of keratin depends upon -S-S- bonds - more –S-S– bonds make nail and bones hard Fibrous Proteins: Collagen - Most abundant proteins in humans (30% of total body protein) - Major structural material in tendons, ligaments, blood vessels, and skin - Organic component of bones and teeth - Predominant structure - triple helix - Rich in proline (up to 20%) – important to maintain structure Globular Proteins: Myoglobin An oxygen storage molecule in muscles. Monomer - single peptide chain with one heme unit Binds one O2 molecule Has a higher affinity for oxygen than hemoglobin. Oxygen stored in myoglobin molecules serves as a reserve oxygen source for working muscles Globular Proteins: Hemoglobin - An oxygen carrier molecule in blood - Transports oxygen from lungs to tissues - Tetramer (four peptide chains) - each subunit has a heme group - Can transport up to 4 oxygen molecules at time - Iron atom in heme interacts with oxygen - - Protein Classification Based on function Proteins play crucial roles in most biochemical processes. The diversity of functions exhibited by proteins far exceeds the role of other biochemical molecules The functional versatility of proteins stems from: Ability to bind small molecules specifically and strongly Ability to bind other proteins and form fiber-like structures, and Ability integrated into cell membranes A k i | 23 CHEM113 – LECTURE Major Categories of Proteins Based on Function - Catalytic proteins: Enzymes are best known for their catalytic role. Almost every chemical reaction in the body is driven by an enzyme - Defense proteins: Immunoglobulins or antibodies are central to functioning of the body’s immune system. - Transport proteins: Bind small biomolecules, e.g., oxygen and other ligands, and transport them to other locations in the body and release them on demand. - Messenger proteins: transmit signals to coordinate biochemical processes between different cells, tissues, and organs. Insulin and glucagon - regulate carbohydrate metabolism Human growth hormone – regulate body growth - Contractile proteins: Necessary for all forms of movement. Muscles contain filament-like contractile proteins (actin and myosin). Human reproduction depends on the movement of sperm – possible because of contractile proteins. - Structural proteins: Confer stiffness and rigidity Collagen is a component of cartilage a Keratin gives mechanical strength as well as protective covering to hair, fingernails, feathers, hooves, etc. - Transmembrane proteins: Span a cell membrane and help control the movement of small molecules and ions. Have channels – help molecules can enter and exist the cell. Transport is very selective - allow passage of one type of molecule or ion. - Storage proteins: Bind (and store) small molecules. Ferritin - an iron-storage protein - saves iron for use in the biosynthesis of new hemoglobin molecules. Myoglobin - an oxygen-storage protein present in muscle - Regulatory proteins: Often found “embedded” in the exterior surface of cell membranes - act as sites for receptor molecules Often the molecules that bind to enzymes (catalytic proteins), thereby turning them “on” and “off,” and thus controlling enzymatic action. - Nutrient proteins: Particularly important in the early stages of life - from embryo to infant. Casein (milk) and oval albumin (egg white) are nutrient proteins Milk also provides immunological protection for mammalian young. Protein Hydrolysis Hydrolysis of proteins - reverse of peptide bond formation: Results in the generation of an amine and a carboxylic acid functional groups. Digestion of ingested protein is enzyme-catalyzed hydrolysis Free amino acids produced are absorbed into the bloodstream and transported to the liver for the synthesis of new proteins. Hydrolysis of cellular proteins and their resynthesis is a continuous process. Protein Denaturation - Partial or complete disorganization of protein’s tertiary structure - Cooking food denatures the protein but does not change protein nutritional value - Coagulation: Precipitation (denaturation of proteins) Egg white - a concentrated solution of protein albumin - forms a jelly when heated because the albumin is denatured - Cooking: Denatures proteins – Makes it easy for enzymes in our body to hydrolyze/digest protein Kills microorganisms by denaturation of proteins Fever: >104ºF – the critical enzymes of the body start getting denatured Glycoproteins - Conjugated proteins with carbohydrates linked to them: Many of plasma membrane proteins are glycoproteins Blood group markers of the ABO system are also glycoproteins Collagen and mmunoglobulins are glycoproteins Collagen - glycoprotein Most abundant protein in human body (30% of total body protein) Triple helix structure Rich in 4-hydroxyproline (5%) and 5-hydroxylysine (1%) — derivatives Some hydroxylysines are linked to glucose, galactose, and their disaccharides – help in aggregation of collagen fibrils. Immunoglobulins - Glycoproteins produced as a protective response to the invasion of microorganisms or foreign molecules antibodies against antigens. - Immunoglobulin bonding to an antigen via variable region of an immunoglobulin occurs through hydrophobic interactions, dipole – dipole interactions, and hydrogen bonds. Lipoprotein - a conjugated protein that contains lipids in addition to amino acids - Major function - help suspend lipids and transport them through the bloodstream - Four major classes of plasma lipoproteins: Chylomicrons: Transport dietary triacylglycerols from intestine to liver and to adipose tissue. Very-low-density lipoproteins (VLDL): Transport triacylglycerols synthesized in the liver to adipose tissue. Low-density lipoproteins (LDL): Transport cholesterol synthesized in the liver to cells throughout the body. High-density lipoproteins (HDL): Collect excess cholesterol from body tissues and transport it back to the liver for degradation to bile acids. 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