Macromolecules Biology Lecture Notes PDF

Topic 4 The Structure and Function of Macromolecules in the living cell PowerPoint Lectures for Biology, Seventh Edition Neil Campbell and Jane Reece Lectures by Chris Romer o Copyright © 2005 Pearson Education, Inc. pub lishing as Benjamin Cummings  Learning objectives (LOBs) 1. Describe...

Topic 4 The Structure and Function of Macromolecules in the living cell PowerPoint Lectures for Biology, Seventh Edition Neil Campbell and Jane Reece Lectures by Chris Romer o Copyright © 2005 Pearson Education, Inc. pub lishing as Benjamin Cummings  Learning objectives (LOBs) 1. Describe the structure and function of different types of biologically important carbohydrates in living organisms. 2. Describe the structure and function of different types of biologically important lipids in living organisms. 3. Name the 20 amino acids and identify the group that they belong to (polar, non-polar, electrically charged). 4. Describe the structure and function of different types of proteins in living organisms, including the 4 different levels of protein structure. 5. Discuss the role of the change in primary protein structure in the pathogenesis of sickle cell anaemia. 6. Describe and compare the structure and function of DNA and RNA. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings  Reading Campbell Biology, Chapter 5 Alberts et al, Molecular Biology of the Cell, Chapter 10 (figures) Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings  The molecules of life Small organic molecules are joined together to form larger molecules within cells Macromolecules: - large molecules with complex structures - composed of thousands of covalently connected atoms Figure 5.1 Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings The Molecules of Life All living organisms are made up of 4 classes of biological macromolecules: - Carbohydrates - Lipids - Proteins - Nucleic acids Molecular structure and function of macromolecules are highly related Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings  Biological molecules Biomolecule: any chemical molecule that is a structural or functional component of living organisms Chemical elements that participate in the synthesis of biomolecules structures: - mostly carbon (C) and hydrogen (Η) - also oxygen (O), nitrogen (N), sulphur (S) and phosphorus (P) Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Macromolecules are polymers built from monomers A polymer is a long molecule consisting of many similar building blocks These small building-block molecules are called monomers 3 of the 4 classes of life’s organic molecules are polymers: – Carbohydrates – Proteins – Nucleic acids Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings  Cells consist of four different types of macromolecules Major subunit Macromolecule MONOSACCHARIDES CARBOHYDRATES FATTY ACIDS LIPIDS AMINO ACIDS PROTEINS NUCLEOTIDES NUCLEIC ACIDS Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings The Synthesis and Breakdown of Polymers Dehydration reaction (condensation reaction): - 2 monomers bond together through the loss of a water molecule Enzymes are macromolecules that speed up the dehydration process Hydrolysis: - reaction that is the reverse of the dehydration reaction - disassembles polymers to monomers Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings  The Synthesis and Breakdown of Polymers Monomers form larger molecules by condensation reactions called dehydration reactions HO 1 2 3 H HO H Short polymer Unlinked monomer Dehydration removes a water H2O molecule, forming a new bond HO 1 2 3 4 H Longer polymer Figure 5.2A (a) Dehydration reaction in the synthesis of a polymer Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings  The Synthesis and Breakdown of Polymers Polymers can disassemble (break down) to monomers by hydrolysis HO 1 2 3 4 H Hydrolysis adds a water H2O molecule, breaking a bond HO 1 2 3 H HO H Figure 5.2B (b) Hydrolysis of a polymer Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings The Diversity of Polymers Each cell has thousands of different kinds of macromolecules Macromolecules vary among cells of an organism, vary more within a species, and vary even more between species Different polymers can be built from a small set of monomers Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings  Biomolecules: 4 categories 1.Carbohydrates 2. Νucleicacids 3.Proteins 4.Lipids Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings  1. Carbohydrates Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings  1. Carbohydrates Carbohydrates serve as fuel and building material Carbohydrates: – Carbo- (carbon) and hydro- (water) – Molecular formula: multiples of the unit (CH2O) => (CH2O)n Examples: - Pentoses: C5H10O5 (ribose, deoxyribose) (n=5) - Hexoses: C6H12O6 (glucose, fructose) (n=6) Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings  Carbohydrates: monosaccharides and polysaccharides Biologically important carbohydrates are also called sugars Monosaccharides: the simplest carbohydrates, single sugars (monomers) Polysaccharides: carbohydrate polymers composed of many sugar building blocks Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Carbohydrates: monosaccharides and polysaccharides SINGLE SUGARS CARBOHYDRATES (MONOSACCHARIDES) (POLYSACCHARIDES) Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings  4 categories of carbohydrates: 1. Mοnosaccharides: e.g. glucose and fructose (CH2O)n where n = 3-7 2. Disaccharides: made by 2 monosaccharides e.g. maltose, sucrose, and lactose 3. Οligosaccharides: composed by 20-30 monosaccharides 4. Polysaccharides: composed by many glucose subunits e.g. starch, glycogen, cellulose Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Monosaccharides (Sugars) Glucose (C6H12O6) is the most common monosaccharide Monosaccharides serve as: - fuel for cells - raw material for building molecules Monosaccharides are classified by: – The location of the carbonyl group (as aldose or ketose) – The number of carbons in the carbon skeleton Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings  Examples of monosaccharides Triose sugars Pentose sugars Hexose sugars (C3H6O3) (C5H10O5) (C6H12O6) Depending on the H O H O H O H O location of the H C C OH H C C OH H C C OH H C C OH >C=O group a Aldoses H C OH H C OH HO C H HO C H H H C OH sugar can be an H H C C OH OH H C OH HO H C C H OH Glyceraldehyde aldose (at the end) H H C OH H C OH Ribose H H or a ketose (not at Glucose Galactose the end) H H H H C OH H C OH H C OH Sugars have many C O C O C O Ketoses H C OH H C OH HO C H –OH groups H H C OH H C OH Dihydroxyacetone H C OH H C OH H H C OH Ribulose H Figure 5.3 Fructose Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings  The structure and classification of some monosaccharides Trioses (C3H6O3) Pentoses (C5H10O5) Hexoses (C6H12O6) When the carbonyl is at the end = aldose Glyceraldehyde Ribose Glucose Galactose When the carbonyl is in the middle= Dihydroxyacetone ketose Ribulose Fig. 5-3 Fructose Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings  Monosaccharides: structure May be linear but in aqueous solutions many sugars form rings H O 1C 6CH OH 2 6CH OH 2 2 CH2OH H C OH 5C O H 5C O 6 3 H H H H H O 5 H HO C H H H H 4C 1C 4C 1C 4 4 1 OH H OH H OH H C OH O HO 3 2 OH 5 OH 2C OH 3C 2C OH 3 C H C OH H OH 6 H OH H OH H C OH H Figure 5.4 (a) Linear and ring forms. Chemical equilibrium between the linear and ring structures greatly favors the formation of rings. To form the glucose ring, carbon 1 bonds to the oxygen attached to carbon 5. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Disaccharides (Sugars) Consist of 2 monosaccharides A disaccharide is formed when a dehydration reaction joins 2 monosaccharides This covalent bond is called a glycosidic linkage Common disaccharides: Glucose + glucose = maltose Glucose + galactose = lactose Glucose + fructose = sucrose Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings  Examples of disaccharides (a) Dehydration reaction in the synthesis of maltose. The bonding CH2OH CH2OH CH2OH CH2OH of two glucose units O O O O forms maltose. The H H H H H H 1–4 H H H H H 1 glycosidic 4 H glycosidic link joins the number 1 carbon OH H OH OH H OH H linkage OH H HO HO OH of one glucose to the HO O OH number 4 carbon of the second glucose. H OH H OH H OH H OH Joining the glucose H2O monomers in a Glucose Maltose Glucose different way would result in a different disaccharide. CH2OH CH2OH CH2OH CH2OH H O O H O H 1–2 O H H H H H 1 glycosidic 2 (b) Dehydration reaction OH H H HO OH H linkage H HO OH HO in the synthesis of HO CH2OH HO O CH2OH sucrose. Sucrose is a disaccharide formed H OH OH H H OH OH H from glucose and fructose. Notice that fructose, H2O though a hexose like Glucose Fructose Sucrose glucose, forms a five-sided ring. Figure 5.5 Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Polysaccharides Polysaccharides: - the polymers of sugars -have storage and structural roles The structure and function of a polysaccharide are determined by its sugar monomers and the positions of glycosidic linkages Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings  Storage Polysaccharides Starch and Glycogen: – Polymers consisting entirely of glucose monomers Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Starch The major storage polysaccharide in plants Consists entirely of glucose monomers Plants store excess starch as granules within chloroplasts and other plastids (called amyloplasts) Consists of 2 polysaccharides: amylose (20-30%) and amylopectin (70-80%) Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings  Starch structure α (1→4) glycosidic linkage (unbranched) α (1→4) and α (1→6) glycosidic linkages (branched) Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings  Starch in plant cells Amyloplasts Cell walls Amyloplasts (starch granules) in potato cells (black -I2/KI staining) Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings  Starch in nutrition Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings  Glycogen Glycogen is a storage polysaccharide in animals Consists of glucose monomers Humans and other vertebrates store glycogen mainly in liver and muscle cells as cytosolic granules Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings  Glycogen structure branch point Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings  Structural Polysaccharides Cellulose: in plant cell walls Chitin: in fungal cell walls and arthropod exoskeleton Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Cellulose Cellulose: a glucose polymer The major component of plant cell wall Cellulose is a glucose polymer but has different glycosidic linkages from starch A cellulose molecule is an unbranched β-glucose polymer. The difference is based on 2 ring forms for glucose: alpha () and beta () Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings  Cellulose structure Different glycosidic linkages than starch H O α-glucose: CH2OH C CH2OH β-glucose: The –OH group at C- H O H H C OH H O OH The –OH group at H H 2 is in the same side 4 OH H HO C H 4 OH H 1 C-2 is in different HO OH H C HO H OH of the plane with H OH H OH side of the plane C –OH group at C-1  glucose H OH than the –OH group H C OH  glucose in C-1 (a)  and  glucose ring structures CH2OH CH2OH CH2OH CH2OH O O O O Starch is helical OH 1 4 OH 1 O 4 OH 1 O 4 OH 1 O O due to α-linkage HO OH OH OH OH (b) Starch: 1– 4 linkage of  glucose monomers CH2OH OH CH2OH OH O O Cellulose is straight OH 1 O 4 OH O OH O OH HO due to β-linkage OH O O OH CH2OH OH CH2OH (c) Cellulose: 1– 4 linkage of  glucose monomers Figure 5.7 A–C Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings  Polysaccharide structure All α-glucose monomers have the same orientation Starch and glycogen Cellulose and chitin Each β-glucose/NAG monomer is inverted in relation to the previous and the next monomer Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings  Cellulose in plant cell walls About 80 cellulose Cellulose microfibrils molecules associate in a plant cell wall Microfibril to form a microfibril, the Cell walls main architectural unit of the plant cell wall. 0.5 m Plant cells CH2OH OH CH2OH OH O O O O OH OH OH OH O O O OO O CH OH OH CH2OH H 2 Cellulose CH2OH OH CH2OH OH molecules O O O O OH OH OH OH O Parallel cellulose molecules are O O O O O CH OH OH CH held together by hydrogen 2 2OH H bonds between hydroxyl CH2OH OH CH2OH OH O O O O groups attached to carbon OH O OH OH O O OH O atoms 3 and 6. O CH OH O A cellulose molecule OH CH2OH H 2 is an unbranched  Figure 5.8  Glucose glucose polymer. monomer Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings  Cellulose Cellulose is difficult to digest Humans can digest starch but not cellulose Cellulose in human food passes through the digestive tract as insoluble fiber Some microbes have enzymes that digest cellulose => Many herbivores (e.g. cows and termites) have microbes in their stomachs (symbiotic relationship) that can break down cellulose Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings  Cellulose Cows have microbes in their stomachs to facilitate cellulose digestion Figure 5.9 Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings  Chitin Another important structural polysaccharide – Found in the exoskeleton of arthropods and fungal cell walls – Used to make surgical thread CH2OH O H OH H OH H OH H H NH C O CH3 (a) The structure of the (b) Chitin forms the exoskeleton (c) Chitin is used to make a chitin monomer of arthropods. This cicada strong and flexible surgical (NAG= N-acetyl-glucosamine). is molting, shedding its old thread that decomposes after exoskeleton and emerging the wound or incision heals. Figure 5.10 A–C in adult form. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings  Polysaccharide structure Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings  Polyssacharides: structure and function comparison Starch Glycogen Cellulose Chitin Function Storage Storage Structural Structural polysaccharide polysaccharide polysaccharide polysaccharide Cell type Plant cell Animal cells Plant cell wall Fungal cell amyloplasts (Cytosolic wall, arthropod (starch granules) exoskeleton granules) Monomer α-glucose α-glucose β-glucose β-NAG (Ν- type acetyl- glucosamine) structure helical helical linear linear Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings  2. Lipids Lipids: – The one class of large biological molecules that do not consist of polymers – They are hydrophobic: little or no affinity for water Biologically important lipids: I. Fats II. Phospholipids III. Steroids Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings  Lipids Major subunit Macromolecule FATTYACIDS LIPIDS Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings  Fats and Nutrition Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Lipids Lipids are hydrophobic because they consist mostly of hydrocarbons, which form non-polar covalent bonds Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings  I. Fats Triglycerides: the storage form of fat - Structure : glycerol + 3 fatty acids Fats are hydrophobic => they separate from water because water molecules form hydrogen bonds with each other and exclude the fats H H H H H H H H O H H H H H H H H H COH C C C C C C C C H C C C C C C C C HO H H H H H H H H H H H H H H H H C OH Fatty acid H C OH (palmitic acid) H Triglyceride Glycerol (a) Dehydration reaction in the synthesis of a fat structure Ester linkage (bond) H O H H H H H H H H H H H H H H H H C O C C C C C C C C C C H C C C C C C H H H H H H H H H H H H H H H O H H H H H H H H H H H H H H H H C O C C C C C C C C H C C C C C C C C H H H H H H H H H H H H H H H O H H H H H H H H H H H H H H H H C O C C C C C C C C H C C C C C C C C H H H H H H H H H H H H H H H H Figure 5.11 (b) Fat molecule (triacylglycerol) Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Fatty acids Fatty acid structure: R- COOH R= long hydrocarbon chain (usually 16-18 carbons) Fatty acids vary in length (number of carbons) and in the number and locations of double bonds Saturated fatty acids have no double bonds Unsaturated fatty acids have 1 or more double bonds Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings  Fatty acid structure Stearic acid(18 C) Palmitic acid (16 C) Οleic acid (18 C) Alberts et al, Molecular Biology of the Cell. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings  Saturated fatty acids Have the maximum number of hydrogen atoms possible (no double bonds) Molecular formula: CH3(CH2)nCOOH Mostly found in animals Fats made from saturated fatty acids are called saturated fats and are solid at room temperature Example: Stearic acid (18:0): Stearic acid (18:0) 18 C, 0 double bonds Figure 5.12 (a) Saturated fat and fatty acid Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Unsaturated fatty acids Mostly found in plants and fish Fats made from unsaturated fatty acids are called unsaturated fats or oils They are liquid at room temperature Oleic acid cis double bond Figure 5.12(b) Unsaturated fat and fatty acid causes bending Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings  Saturated and unsaturated fatty acids examples (4:0) (18:1) (18:2) Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings  Saturated fats: health risks A diet rich in saturated fats may contribute to cardiovascular disease through plaque deposits. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings  Unsaturated vs Saturated Fats Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings  Unsaturated vs Saturated Fats: health effects Saturated and unsaturated fats have different molecular effects on the liver Unsaturated fats signal to the liver to take up cholesterol from the blood => improve cholesterol levels Unsaturated fats actually reduce LDL- bound (“bad”) cholesterol levels and maintain HDL- bound (“good”) cholesterol. Saturated fats directly increase LDL-bound (“bad”) cholesterol levels. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings  Do we need fat? The major function of fats is energy storage Humans and other mammals store their fat in adipose cells Adipose tissue also cushions vital organs and insulates the body Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings  II. Phospholipids Have only 1 or 2 fatty acids and a phosphate group instead of a third fatty acid 2 types: (a)Phosphoglycerides: glycerol + 2 fatty acids + phosphate + organic molecule (b) Phosphosphingolipids: sphingosine + 1 fatty acid + phosphate + organic molecule Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings  Phospholipids Function: important components of biological membranes Common membrane phospholipids: Phospholipid name Alcohol Phosphatidyl-choline Glycerol Phosphatidyl-ethanolamine Glycerol Phosphatidyl-serine Glycerol Phosphatidyl-inositol Glycerol Sphingomyelin Sphingosine Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings  Phospholipid structure Amphipathic molecules: consist of a hydrophilic “head” and hydrophobic “tails” CH2 + N(CH ) 3 3 Choline CH2 O O P O– Phosphate O CH2 CH CH2 Glycerol O O C O C O Fatty acids Hydrophilic head Hydrophobic tails (c) Phospholipid (a) Structural formula (b) Space-filling model Figure 5.13 symbol Example: Phosphatidyl-choline structure Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings  Phospholipids choline ethanolamine serine Fatty acids inositol * Phosphatidyl-inositol Alberts Copyright ©et 2005al, Molecular Pearson Biology Education, Inc. publishing of the as Benjamin Cell. *Fatty chain is part of the sphingosine molecule Cummings  Phospholipids structure: sphingomyelin Phosphocholine (Phosphate + choline) Fatty chain (part of the sphingosine molecule) Sphingosine Fatty acid sphingomyelin (Index: Black= Sphingosine Red= Phosphocholine Blue= Fatty acid) Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings  Phospholipids structure: Bilayer arrangement When phospholipids are added to water, they self-assemble into a bilayer, with the hydrophobic tails pointing toward the interior The structure of phospholipids results in a bilayer arrangement found in cell membranes => Phospholipids are the major component of all cell membranes WATER Hydrophilic head WATER Hydrophobic tail Figure 5.14 Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings  III. Steroids Steroids are lipids characterized by a carbon skeleton consisting of four fused rings Cholesterol is a steroid found in animal cell membranes - precursor for some hormones H3C CH3 CH3 CH3 CH3 Cholesterol structure Figure 5.15 HO Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings  Steroid hormones Several other hormones are also steroids (steroid hormones) Steroid hormones: e.g. androgens and estrogens Estradiol Testosterone Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings  Cholesterol: health risks Although cholesterol is essential in animals, high levels in the blood may contribute to cardiovascular disease Role of “ good” cholesterol vs “bad” cholesterol in cardiovascular disease Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings  Cholesterol: health risks Cholesterol: circulates in blood bound to lipoproteins (LDL: low density lipoproteins, HDL: high density lipoproteins) Lipoproteins are recognized by their receptor on the plasma membrane of liver cells (hepatocytes)  The cells take in the lipoproteins-cholesterol vesicles  Cholesterol is released into the liver cells by receptor- mediated endocytosis HDL- bound cholesterol ="good" cholesterol, protein > cholesterol => travels fast into bloodstream and targeted-deposited directly into the liver. LDL-bound cholesterol= "bad" cholesterol, cholesterol > protein => travels slower into bloodstream and leaves bits and pieces around => atheromatic plaque (cholesterol+ platelets) Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings  3. Proteins Proteins have many structures => a wide range of functions Proteins account for more than 50% of the dry mass of most cells Protein functions: structural support storage transport cellular communications movement defense against foreign substances (immune response) Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings  AMINO ACIDS PROTEINS Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings  Proteins and Nutrition Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings  Protein functions Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings  Enzymes A specific type of protein that acts as a catalyst, speeding up chemical reactions 1 Active site is available for 2 Substrate binds to a molecule of substrate, the enzyme. Substrate reactant on which the enzyme acts. (sucrose) Glucose Enzyme OH (sucrase) H2O Fructose H O 4 Products are released. 3 Substrate is converted Figure 5.16 to products. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Polypeptides: Amino Acid Polymers A polypeptide is a polymer of amino acids A protein consists of one or more polypeptides Polypeptides range in length from a few to more than a thousand monomers Each polypeptide has a unique linear sequence of amino acids Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Amino acids, polypeptides, proteins Amino acids Polypeptides Proteins Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings  Amino Acid Monomers Amino acids: – organic molecules possessing both carboxyl and amino groups – differ in their properties due to differing side chains, called R groups General structure of aminoacids Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings  α carbon Amino Carboxyl group group Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Protein in food Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Proteins consist of 20 different amino acids The structure of a protein is determined by the sequence of amino acids Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings  The 20 aminoacids 3 types: Polar, Nonpolar and Electrically charged CH3 CH3 CH3 CH3 CH CH2 CH3 H CH3 CH CH2 H3C CH O O O O O H3N+ C C H3N+ C C H3N+ C C H3N+ C C H3N+ C C O– O– O– O– O– H H H H H Glycine (Gly) Alanine (Ala) Valine (Val) Leucine (Leu) Isoleucine (Ile) Nonpolar CH3 CH2 S H2C CH2 NH O CH2 H2N C C CH2 CH2 CH2 O– O O O H H3N+ C C H3N+ C C H3N+ C C O– O– O– H H H Methionine (Met) Phenylalanine (Phe) Tryptophan (Trp) Proline (Pro) Figure 5.17 Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings  The 20 Aminoacids OH NH2 O NH2 O C OH SH C CH2 Polar OH CH3 CH2 CH CH2 CH2 CH2 CH2 O O O O O O H3N+ C C H3N+ C C H3N+ C C H3N+ C C H3N+ C C H3N+ C C O– O– O– O– O– O– H H H H H H Threonine Cysteine Tyrosine Asparagine Glutamine Serine (Ser) (Tyr) (Thr) (Cys) (Asn) (Gln) Acidic Basic + –O O– O NH3 NH2 NH+ O C C CH2 C NH2+ NH Electrically CH2 CH2 CH2 CH2 O CH2 charged O H3N+ C C CH2 CH2 CH2 H3N+ C C O O– C O– H3N+ C CH2 CH2 H H O O– CH2 H H3N+ C C O O– C C H H3N+ O– H Aspartic acid Glutamic acid Lysine (Lys) Arginine (Arg) Histidine (His) (Asp) (Glu) Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Polypeptides: peptide bond formation Aminoacids are linked by covalent bonds called peptide bonds to form polypeptides R1= side chain 1 R2= side chain 2 Aminoacid 1 Aminoacid 2 dipeptide Dipeptide Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings  Peptide bond formatiion OH Peptide bond OH SH CH2 CH2 CH2 H H H H C C N C C OH H N C C OH H O H O H O (a) Dehydration H2O reaction OH OH Side Peptide SH chains CH2 CH2 bond CH2 H H H H N C C N C C N C C OH Backbone H O H O H O Amino end Carboxyl end Figure 5.18 (b) (N-terminus) (C-terminus) Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Protein Structure and Function The amino acid sequences of polypeptides: - were first determined using chemical means - can now be determined by automated machines A functional protein consists of one or more polypeptides twisted, folded, and coiled into a unique shape The sequence of amino acids determines a protein’s 3-D structure A protein’s structure determines its function Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings  Protein Conformation and Function A protein’s specific conformation determines how it functions Two models of protein conformation Groove (a) A ribbon model Groove Figure 5.19 (b) A space-fillingmodel Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Four Levels of Protein Structure Primary structure: the unique sequence of amino acids of a protein Secondary structure: consists of coils and folds in the polypeptide chain (α-helices and β-pleated sheets) Tertiary structure: the 3-dimensional structure (shape) of a protein determined by the interactions among various side chains (R groups) Quaternary structure: results when a protein consists of multiple polypeptide chains (subunits) Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings  Primary structure The unique sequence of amino acids in a polypeptide GlyProThr Gly +H N Thr 3 Gly Amino acid Amino LeuPro CysLysSeu Glu subunits end Met Val Lys Val Leu Asp AlaVal ArgGly Ser Pro Ala GluLle Asp Thr Lys Ser Tyr AlaLys Trp GlyLeu lle Ser ProPheHis Glu His Ala Glu Val Ala ThrPheVal Asn lle Asp Thr Tyr Ala Arg Ser Arg Ala GlyPro Leu Leu Ser Pro SerTyr Tyr ThrSer Thr Ala Val o Val Glu c ThrAsnPro Lys o– Figure 5.20 Carboxyl end Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings  Secondary structure The folding or coiling of the polypeptide into a repeating configuration Includes the -helix and the -pleated sheet  pleated sheet O H H O H H OH H O H H R R R Amino acid CCN C C N CC N C C N CN CC N CC N subunits R R R CC N R CC H OHH OHH OHH O R R R R O O HHC O C HH O H H C C C N H C NH CNHC N C NH C N C NHCN H C H C H O C H C O O O C R R R R H R H C C N H O CN H O C H  helix N N H OC O C HCRHC HCRHC R R N HO C N H O C O C N H O C NH C C R H R H Figure 5.20 Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings  Tertiary structure The overall 3-dimensional shape of a polypeptide Results from interactions between amino acids and R (side chain) groups Hydrophobic interactions and CH van der Waals CH22 CH H3C CH3 interactions O Hydrogen H H3C CH3 Polypeptide bond O CH backbone HO C CH2 CH2 S S CH2 Disulfide bridge O CH2 NH 3+ -O C CH2 Ionic bond Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings  Tertiary structure: types of interactions Disulphide bonds Hydrogen bonds van der Waals interactions Electrostatic interactions (ionic bonds) Hydrophobic interactions Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings  Disulphide bonds Covalent bonds between two –SH groups Disulfide bonds (bridges) in a protein Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings  Quaternary structure The overall protein structure that results from the aggregation of 2 or more polypeptide subunits (polypeptide chains) Polypeptide Tertiary Structure Quaternary Structure chain Fig. 5-21e Collagen  Chains Iron Heme  Chains Haemoglobin Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings  Four Levels of Protein Structure Tertiary Quaternary Primary Structure Structure Secondary (interactions Structure (interactions Structure between two (unique among amino (coils and or more amino acid acid side folds) polypeptides) sequence) chains) Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings  Primary Secondary Tertiary Quaternary Structure Structure Structure Structure β pleated sheet +H N 3 Amino end Examples of amino acid subunits α helix Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings  Protein-Folding: chaperones Most proteins go through several intermediate states until they acquire a stable conformation Chaperones (chaperonins): proteins that assist and maintain the proper folding of other proteins Location: cytosol, mitochondria, chloroplasts, ER. Correctly Polypeptide folded protein Cap Hollow cylinder Chaperonin Steps of Chaperonin 2 The cap attaches, causing 3 The cap comes (fully assembled) Action: the cylinder to change shape in off, and the properly 1 An unfoldedpoly- such a way that it creates a folded protein is peptide enters the hydrophilic environment for the released. Figure 5.23 cylinder from one end. folding of the polypeptide. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings  Protein structure determination X-ray crystallography: used to determine a protein’s three-dimensional structure X-ray diffraction pattern Photographic film Diffracted X-rays X-ray X-ray source beam Crystal Nucleic acid Protein Figure 5.24 (a) X-ray diffraction pattern (b) 3D computer model Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings  Sickle-Cell Disease: Example of a disease caused by simple change in primary structure A slight change in primary structure can affect a protein’s structure and ability to function Sickle-cell disease: – Inherited blood disorder – Results from a single amino acid substitution in the protein haemoglobin in the red blood cells (due to Glu → Val mutation) Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings  Ηaemoglobin Haemoglobin is a globular protein consisting of 4 polypeptides: 2 alpha and 2 beta chains β Chains Iron Heme α Chains Hemoglobin Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Fig. 5-22 Normal hemoglobin Sickle-cell hemoglobin Primary Primary Val His Leu Thr Pro Glu Glu Val His Leu Thr Pro Val Glu structure structure 1 2 3 4 5 6 7 1 2 3 4 5 6 7 Exposed Secondary Secondary hydrophobic and tertiary β subunit and tertiary region β subunit structures structures α α β β Quaternary Normal Quaternary Sickle-cell structure hemoglobin structure hemoglobin (top view) α β β α Function Molecules do Function Molecules not associate interact with with one one another and another; each crystallize into carries oxygen. a fiber; capacity to carry oxygen is greatly reduced. 10 µm 10 µm Red blood Normal red blood Red blood Fibers of abnormal cell shape cells are full of cell shape hemoglobin deform individual red blood cell into hemoglobin sickle shape. moledules, each carrying oxygen. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Fig. 5-22c 10 µm 10 µm Normal red blood Fibers of abnormal cells are full of hemoglobin deform individual red blood cell into hemoglobin sickle shape. molecules, each carrying oxygen. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Sickle cell disease Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Protein Conformation Protein conformation depends on the physical and chemical conditions of the protein’s environment Denaturation: the loss of a protein’s native conformation due to unravelling => loss of function A denatured protein is biologically inactive Protein denaturation factors: - pH changes - salt concentration changes - temperature changes - other environmental factors Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings  Protein Conformation Denaturation Normal protein Denatured protein Figure 5.22 Renaturation Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings  4. Nucleic acids Nucleic acids store and transmit hereditary information The amino acid sequence of a polypeptide is encoded by a unit of inheritance called a gene Genes: – The units of inheritance – Program the amino acid sequence of polypeptides – Made of DNA (a nucleic acid) Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings  NUCLEOTIDES NUCLEIC ACIDS Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings  The Roles of Nucleic Acids There are two types of nucleic acids: – Deoxyribonucleic acid (DNA) – Ribonucleic acid (RNA) DNA: – Stores information for protein synthesis – Directs RNA synthesis – Directs protein synthesis through mRNA (messenger RNA) Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings  The Roles of Nucleic Acids DNA Protein synthesis 1 Synthesis of occurs in mRNA in the nucleus mRNA ribosomes NUCLEUS CYTOPLASM mRNA 2 Movement of mRNA into cytoplasm Ribosome via nuclear pore 3 Synthesis of protein Amino Polypeptide acids Figure 5.25 Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings  The Structure of Nucleic Acids Nucleic acids: 5’end - exist as polymers called 5’C O polynucleotides 3’C O O 5’C O 3’C OH 3’end Figure 5.26 (a) Polynucleotide, or nucleic acid Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings  The Structure of Nucleic Acids Each polynucleotide consists of monomers called nucleotides Nucleotide = nitrogenous base + pentose sugar + phosphate group Nucleoside Nitrogenous base O 5’C − O P O CH2 O O− 3’C Figure 5.26 Phosphate Pentose group sugar (b) Nucleotide Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings  The Structure of Nucleic Acids 5’ end Nitrogenous bases Pyrimidines 5C 3C Nucleoside Nitrogenous base Cytosine (C) Thymine (T, in DNA) Uracil (U, in RNA) Purines Phosphate group Sugar 5C (pentose) Adenine (A) Guanine (G) 3C (b) Nucleotide Sugars 3’ end (a) Polynucleotide, or nucleic acid Deoxyribose (in DNA) Ribose (in RNA) (c) Nucleoside components: sugars Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings  Nucleotide Monomers Nucleotide monomers Nitrogenous bases consist of: Pyrimidines NH2 O O - nitrogenous base N C CH HN C C CH3 HN C CH CH C CH C CH C CH N O N O N O - pentose sugar H Cytosine Thymine (in DNA) Uracil Uracil(in H (in RNA) RNA) H C T UU - phosphate group Purines