The Structure and Function of Large Biological Molecules Chapter 5

The Structure and Function of Large Biological Molecules Chapter 5 I. The Molecules of Life A. There are four main classes of large molecules 1. Carbohydrates 2. Proteins 3. Lipids 4. Nucleic acids B. Because of their huge size, three of these classes are considered macromolecules: Carbohydrates, Protein and Nucleic Acids C. Large biological molecules exhibit unique emergent properties arising from the orderly arrangement of their atoms - structure determines function II. Macromolecules are Polymers, Built from Monomers A. Macromolecules are chain like molecules called polymers B. A polymer is a long molecule consisting of many similar or identical building blocks liked by covalent bonds! C. Monomers are the repeating units that serve as the building blocks of!! polymers - some monomers have functions outside of the polymers they! make up! D. The synthesis and breakdown of polymers (Figure 5.2) 1. Condensation reaction or dehydration reaction - chemical reaction in which two molecules are covalently bonded to each other through loss of a water molecule 2. Bonds between monomers occur when each monomer contributes part of the water molecule that is lost 3. The dehydration process is facilitated by enzymes which are specialized molecules that speed up chemical reactions in cells 4. Hydrolysis is the process through which polymers are disassembled to form monomers a. It is the opposite of a dehydration reaction b. Hydrolysis means to break using water c. Hydrogen is added to one monomer while the other receives an hydroxyl group E. The diversity of polymers 1. The possible variety of macromolecules is essentially limitless 2. This diversity results in differences between family members, unrelated individuals and different species 3. These diverse polymers are generated from only 40-50 common monomers and a few that occur rarely 4. The arrangement of these monomers is what results in the diversity - similar to constructing hundreds of thousands of words from 26 letters 5. Molecular structure and function can still be grouped by class, each with emergent properties not found in their individual building blocks

III. Carbohydrates Serve as Fuel and Building Material A. Carbohydrates are sugars and polymers of sugars B. Monosaccharides are simple sugars C. Disaccharides are double sugars consisting of two monosaccharides D. Polysaccharides are polymers composed of many monosaccharides E. Sugars (Figure 5.3)!! 1. Monosaccharides generally have molecular formulas that are multiples!! of CH2O!! 2. Glucose (C6H12O6) is the most common monosaccharide and is!! critical in the chemistry of life!! 3. Molecular trademarks of a sugar!!! a. Carbonyl group!!! b. Multiple hydroxyl groups!!! c. Depending on the location of the carbonyl group the sugar is!!! either an aldose or a ketose!!! d. The carbon skeleton will range from 3-7 carbons long and!!! sugars are classified based on that number (hexose, pentose,!!! triose, etc.!!! e. Diversity in monomers also comes from the spatial arrangement!!! of atoms around asymmetric carbons (a carbon attached to four!!! different atoms or groups of atoms)!!! f. Small differences in structure can give very distinctive shapes!!! and behaviors!!! g. Most sugars in solution form rings (Figure 5.4)!! 4. Monosaccharides are major nutrients for cells!!! a. Energy is extracted through a series of reactions in a process!!! known as cellular respiration!!! b. The carbon skeletons of simple sugars are also raw material for!!! the synthesis of other organic molecules!!! c. Sugar molecules not immediately used by the cell are stored as!!! di- and poly-saccharides!! 5. Glycosidic linkage is a covalent bond formed between two!! monosaccharides by a dehydration reaction (Figure 5.5)!! 6. Sucrose is the most prevalent disaccharide a. Consists of glucose and fructose joined together b. Is table sugar c. Used to transport carbohydrates in plants F. Polysaccharides!! 1. Range from a few hundred to a few thousand monosaccharides joined!! together by glycosidic linkages!! 2. Some polysaccharides serve as storage to by hydrolyzed as needed by!! the cell!! 3. Others serve as building material for structures that protect the cell or!! organism!! 4. The structure and function of a polysaccharide is determined by its!! monomers and the positions of its glycosidic linkages

!! 5. Storage polysaccharides a. Sugars are stored for later use in both plants and animals b. Starch is a polymer of glucose monomers (FIgure 5.6a) i. Stored by plants ii. Stored in cellular structures known as plastids which include chloroplasts iii. This a how the plant stockpiles glucose and, therefore, energy iv. The starch can be broken down by hydrolysis v. Humans have an enzyme that allows hydrolysis of starch which provides us nutrients from plants such as potatoes and grains vi. Most glucose monomers in starch are joined by 1-4 linkages (number 1 carbon to a number 4 carbon) vii. The angle of this linkage makes the polymer helical viii. Starch can either be linear (ex. amylose) or branched (ex. amylopectin)!!! c. Glycogen is a polymer of glucose (Figure 5.6b) i. Humans and other vertebrates store glycogen in liver and muscle cells ii. Hydrolysis of glycogen releases glucose when the demand for sugar increases iii. In humans, glycogen stores are deplete in about a day unless replenished through consumption of food 6. Structural polysaccharides!!! a. Strong materials built from sugars!!! b. Cellulose (Figure 5.7) i. Major component of the wall of plant cells ii. Plants produce almost 10 14 kg of cellulose per year iii. Most abundant organic compound on earth iv. Polymer of glucose, but the glycosidic linkages differ from those in starch a) In starch the glucose monomers are in the alpha position, while in cellulose they are in the beta position b) These differing positions give the two molecules distinct three-dimensional shapes c) Starch is mostly helical while cellulose is straight d) Starch can be branched while cellulose is never branched v. Parallel cellulose molecules can be held together through hydrogen bonding of hydroxyl groups resulting in units called microfibrils (Figure 5.8) vi. Microfibrils are a strong building material for plants vii. Cellulose is the major constituent of paper and cotton

viii. Enzymes that hydrolyze starch are unable to hydrolyze cellulose because of their different shapes ix. Few organisms have the enzymes to digest cellulose a) Humans cannot digest cellulose, but it is still necessary for a healthful diet because it stimulates mucus production in the digestive tract allowing smooth passage of food b) Fresh fruits, vegetables and whole grains are rich in cellulose c) On packaging, insoluble fiber refers mainly to cellulose d) Some prokaryotes can digest cellulose into glucose e) Cows harbor a cellulose digesting prokaryote in their rumen, allowing the cow to gain nutrition from cellulose f) The same is true for termites, allowing them to digest wood g) Some fungi can also digest cellulose allowing recycling of elements within the Earth s ecosystems!!! c. Chitin (Figure 5.10) i. Carbohydrate used by arthropods to build exoskeletons ii. Pure chitin is leathery and flexible, but hardens when encrusted with calcium carbonate iii. Also found in many fungi which use it to build their cell walls iv. Similar to cellulose, but has a nitrogen containing appendage IV. Lipids are a Diverse Group of Hydrophobic Molecules A. Lipids share one important trait: they don t mix well or at all with water B. Their hydrophobic behavior is due to their molecular structure C. Consist mostly of hydrocarbon regions D. Include waxes, pigments, fats, phospholipids and steroids E. Fats 1. Are large molecules assembled from smaller molecules by dehydration reactions, but are not polymers (Figure 5.11) 2. Fats consist of a glycerol molecule and fatty acids (Figure 5.11) 3. Glycerol is an alcohol with 3 carbons, each with an hydroxyl group 4. Fatty acids a. Consists of a long carbon skeleton (16-18 carbons long) b. Has a carboxyl group at one end c. Attached to the carboxyl group is a long hydrocarbon chain d. The non polar C-H bonds of the hydrocarbon are the reason fats are hydrophobic 4. To make a fat, 3 fatty acids molecules join to the glycerol by an ester linkage (Figure 5.11)

a. An ester is a bond between an hydroxyl group and a carboxyl group b. Called triglycerides, three individual fatty acids bind to individual hydroxyl groups on the glycerol c. The fatty acids may all be the same or be two or three different kinds 5. Fatty acids vary in length and in the number and locations of double bonds 6. A saturated fatty acid contains no double bonds and, therefore, has the maximum number of hydrogens bonded to the carbon skeleton (Figure 5.12) 7. An unsaturated fatty acid has one or more double bonds formed the removal of hydrogen atoms from the carbon skeleton (Figure 5.12) 8. Unsaturated fatty acids have bends in their structure wherever a cis double bond occurs 9. Fats made from saturated fatty acids are called saturated fats a. Most animal fats are saturated b. Since the tails lack double bonds they are flexible and allow the molecules to pack together tightly resulting in a solid at room temperature c. Examples are lard and butter 10. Fats of plants are generally unsaturated a. Built of one or more types of unsaturated fatty acids b. The bends caused by the cis double bonds prevent the molecules from packing closely together!!! c. Usually liquid at room temperature!!! d. Generally referred to as oils e. Examples are olive oil and cod liver oil f. Hydrogenated vegetable oils have synthetically been made saturated by adding hydrogen - used in things like peanut butter and margarine to keep the lipids from separating into liquid form 11. A diet rich in saturated fats may contribute to atherosclerosis a. Deposits called plaques develop in the walls of blood vessels impeding blood flow and weakening the vessels b. Hydrogenation of vegetable oils results not only in saturation, but trans double bonds c. Trans fats may contribute more than saturated fats to atherosclerosis 12. Fats provide energy storage a. Similar in structure to gasoline molecules and just as rich in energy b. A gram of fat stores more than twice as much energy as a gram of polysaccharide c. In plants, oils are stored in seeds; in humans, fats are stored in adipose cells

d. Fat in adipose tissue also serves as protection for the vital organs and in marine animals, protection from the cold of ocean water F. Phospholipids 1. Essential for cells because they make up the cell membrane 2. Similar to fat molecules except they have 2 fatty acid chains and a phosphate group attached to the hydroxyl groups of glycerol instead of three fatty acid chains (Figure 5.13) 3. Phosphate group has a negative electrical charge and additional small charged or polar molecules can be linked to it 4. Phospholipids have hydrophobic hydrocarbon tails and hydrophilic head consisting of the phosphate group and any attachments 5. Phospholipids naturally self assemble in water to form double layers called lipid bilayers that keep their hydrophobic portions from the water (Figure 5.14) 6. This bilayer forms at the surface of cells forming a boundary between the cell and its external environment G. Steroids 1. Lipids characterized by a carbon skeleton consisting of four fused rings 2. Steroids differ in the chemical groups attached to these rings 3. Cholesterol is a component of cell membranes and is the precursor from which other steroids are synthesized (Figure 5.15) 4. Cholesterol is critical for the synthesis of many hormones, but a high level of cholesterol can contribute to atherosclerosis 5. Both saturated and trans fats affect cholesterol levels V. Proteins Have Many Structures Resulting in a Wide Range of Functions A. Proteins account for more than 50% of the dry mass of most cells B. Are instrumental in almost everything organisms do including structural support, speeding up chemical reactions, storage, transport, cellular communication, movement and defense against foreign substances (Table 5.1) C. Enzymes are proteins that regulate metabolism by acting as catalysts D. Catalysts selectively speed up chemical reactions without being consumed by the reaction (Figure 5.16) E. Proteins are the most structurally sophisticated molecules known F. Vary extensively in structure and function G. Polypeptides 1. All proteins are polymers constructed from a set of 20 amino acids 2. Polymers of amino acids are called polypeptides 3. Proteins consist of one or more polypeptides folded and coiled into a specific three-dimensional structure 4. Amino acid monomers (Figure 5.17) a. All amino acids share a common structure b. Contain both a carboxyl group and an amino group

c. In between is an alpha carbon which is asymmetric (4 different binding partners) and binds to: i. Amino group ii. Carboxyl group iii. Hydrogen iv. A variable group or side chain which differs with each amino acid d. Understand and memorize the structure of the 20 most common amino acids found in Figure 5.17 e. The physical and chemical properties of the side chains determine the unique characteristics of a particular amino acid and determine its functional role in a polypeptide f. Amino acids are generally grouped according to the properties of their side chains (Figure 5.17) i. Non polar, hydrophobic side chains ii. Polar, hydrophilic side chains iii. Acidic amino acids are generally negative in charge at cellular ph and are hydrophilic iv. Basic amino acids are generally positive in charge and are hydrophilic 5. Amino acid polymers a. Amino acids are joined by dehydration reactions between the carboxyl group of one and the amino group of another (Figure 5.18) b. This covalent bond is called a peptide bond c. Polypeptides are formed by repetition of this reaction d. All polypeptides have a free amino group at one end (Amino end or N terminus) and a free carboxyl group at the other (Carboxyl end or C terminus) e. Polypeptide backbone is the repeating sequence of atoms formed when amino acids are linked in peptide bond. This includes all but the side chains f. Polypeptides range in length from a few monomers to a thousand or more g. Each polypeptide has a unique linear sequence of amino acids and, therefore, unique structure H. Protein structure and function 1. The specific activities of proteins result from their three-dimensional architecture 2. Fredrick Sanger was the pioneer of protein sequencing!!! a. Worked on insulin!!! b. Used chemicals to break the polypeptides at specific!!! places into small fragments c. Used chemical methods to determine the amino acid sequence in these small fragments 3. Polypeptide and protein can not be used interchangeably

4. Protein refers to the functional, folded, three-dimensional form of the polypeptide(s) 5. The amino acid sequence determines what the three-dimensional structure will be 6. Polypeptides generally fold spontaneously a. Folding is driven and reinforced by the formation of bonds between parts of the chain, which depends on the amino acid sequence b. Globular proteins are roughly spherical c. Fibrous proteins are shaped like long fibers 7. Structure determines function a. Most protein function is due to the protein s ability to recognize and bind another molecule such as an antibody to a foreign substance (Figure 5.20) or an enzyme to a substrate b. The function of a protein is an emergent property resulting from molecular order! I. Four levels of protein structure (understand and memorize Figure 5.21) 1. All proteins share three levels of structure!!! a. Primary - unique sequence of amino acids!!! b. Secondary - coils or folds in the polypeptide chain due to!!! hydrogen bonding between repeating constituents of the!!! polypeptide backbone (not the side chains)!!! c. Tertiary - overall shape of a polypeptide resulting from!!! interactions between side chains of amino acids! 2. Quaternary structure is the protein structure formed by the interaction of! two or more polypeptide chains aggregated into one functional!! macromolecule J. Sickle-cell disease: a change in primary structure (Figure 5.22) 1. Example of how a change in protein sequence changes structure and function 2. Caused by substitution of one valine for the normal glutamic acid in hemoglobin 3. This abnormal hemoglobin crystalizes resulting in deformation of red blood cells into a sickle shape 4. These sickle shaped cells then clog tiny blood vessels which prevents normal blood flow K. What determines protein structure? 1. Amino acid sequence that spontaneously folds into a three-dimensional shape determined and maintained by the interactions responsible for secondary and tertiary structure 2. Physical and chemical conditions of the protein s environment including ph, salt concentration and temperature 3. Denaturation is the unraveling and loss of native shape of a protein due to physical and chemical conditions (Figure 5.23) 4. Denatured proteins are biologically inactive

5. Denaturation agents include organic solvents and chemicals that disrupt hydrogen bonds, ionic bonds or disulfide bridges 6. Excessive heat causes enough agitation of the protein to disrupt weak interactions 7. It is sometimes possible to renature a protein when the denaturing agent is removed which indicates that the information necessary for building the specific shape of a protein is contained in the protein s primary structure! L. Protein folding in the cell 1. Determining the three dimensional structure is not as simple as looking at the primary structure 2. Proteins probably go through several intermediate steps in the folding process before they reach a stable shape 3. The final structure of the protein does not reveal the stages required to achieve that final form 4. Chaperonins are protein molecules that assist in the proper folding of other proteins (Figure 5.24) a. They do not determine the final structure of a polypeptide b. They protect the polypeptide while it spontaneously folds c. Shaped like a hollow cylinder, the cavity provides shelter for the folding polypeptide d. Mis-folding of polypeptides can be a serious issue in cells!!!! i. Accumulation of mis-folded polypeptides is associated!!!! with!diseases such as Alzheimer s and Parkinson s ii. Systems to check whether proteins are properly folded have been discovered and appear to either refold the misfolded polypeptides or mark them for destruction 5. X-ray crystallography is used to determine the three dimensional structure of a protein!!! a. First used to determine the structures of hemoglobin and a!!! related protein in 1959!!! b. Recently used by Roger Kornberg and colleagues at Stanford to!!! determine the structure of RNA polymerase (Figure 5.25) 6. NMR (nuclear magnetic resonance) is now also used to determine protein structure and does not require protein crystallization 7. More recently, the approach of bioinformatics has been used to predict the three dimensional structures of polypeptides from their amino acid sequences 8. Xray crystallography, NMR spectroscopy and bioinformatics are complementary approaches that give valuable information about protein structure and function VI. Nucleic Acids Store and Transmit Hereditary Information A. The amino acid sequence of a polypeptide is determined by a unit of heredity known as a gene consisting of a nucleic acid called DNA (Figure 5.26) B. The roles of nucleic acids

1. Deoxyribonucleic acid (DNA) and ribonucleic acid (RNA) allow living organisms to reproduce their complex components from one generation to the next 2. DNA a. The genetic material that organisms inherit from their parents b. Directs its own replication c. Directs RNA synthesis and, through RNA, controls protein synthesis d. Each chromosome consists of one long DNA molecule that carries several hundred or more genes e. DNA molecules are copied and passed from one generation of cells to the next during cell division f. Encoded in DNA is the information necessary for all of a cell s activities g. Proteins implement the genetic programs 3. RNA a. Each gene directs synthesis of an mrna ( messenger RNA) b. The mrna molecule interacts with the cells protein synthesizing machinery to direct production of a polypeptide which folds into a protein c. Protein synthesis occurs at sites called ribosomes which are found in the cytoplasm d. mrna moves genetic information from the nucleus where DNA is present to the ribosomes in the cytoplasm e. In prokaryotes, which do not have a nucleus, RNA is still used to move genetic information from the DNA to ribosomes where it is translated into amino acid sequences f. RNA also plays many other roles in the cell! C. The structure of nucleic acids (Figure 5.27)! 1. Macromolecules that exists as polymers called polynucleotides! 2. Polynucleotides are made up of monomers called nucleotides!! composed of three parts a. A nitrogenous base b. A five carbon sugar (pentose) c. A phosphate group d. The nitrogenous base and pentose comprise a nucleoside! 3. Nucleotide monomers a. There are two families of nitrogenous bases i. Pyrimidines have a six-membered ring of carbon and nitrogen atoms - members of this family are cytosine (C) thymine (T) and uracil (U) ii. Purines have a six-membered ring fused to a fivemembered ring - members of this family are guanine (G) and adenine (A) iii. The specific purines and pyrimidines differ in the chemical groups attached to the rings

iv. Adenine, guanine and cytosine are found in both RNA and DNA, while thymine is found only in DNA and uracil only in RNA b. There are two types of pentose used in nucleic acids i. Ribose is in the nucleotides of RNA ii. Deoxyribose is in the nucleotides of DNA iii. Deoxyribose lacks an oxygen atom on the second carbon in the ring compared to ribose c. A phosphate group is attached to the 5 carbon of the sugar to form a nucleoside monophosphate also know as a nucleotide! 4. Nucleotide polymers a. Adjacent nucleotides are joined together by a phosphodiester bond b. A phosphodiester bond occurs when a phosphate group bonds to the sugars of two nucleotides c. This results in a backbone with a repeating pattern of sugarphosphate units d. One end of the backbone has a phosphate attached to a 5 carbon (5 end) while the other end has an hydroxyl group on the 3 carbon (3 end) e. DNA is a direction molecule from 5 to 3 f. The nitrogenous bases are appendages off of the sugarphosphate backbone g. The sequence of bases is unique for each gene and provides very specific information to the cell h. The number of possible base sequences is essentially limitless i. The linear order of bases in a gene specifies the amino acid sequence and, therefore, the primary structure of polypeptide, which, in turn, specifies the three dimensional structure and function of the protein! D. The DNA double helix (Figure 5.28) 1. RNA molecules consist of a single polynucleotide chain 2. DNA molecules are comprised of two polynucleotides that spiral around an imaginary axis to form a double helix 3. The double helix structure of DNA was proposed by James Watson and Francis Crick in 1953 4. The two polypeptides in the helix run in opposite directions making them antiparallel 5. The sugar-phosphate backbone is on the outside of the helix while the nitrogenous bases are paired on the inside 6. The two polypeptide chains are held together by hydrogen bonds between the paired bases and by van der Waals interactions between the stacked bases 7. Adenine always pairs with thymine while guanine always pairs with cytosine, therefore, if you know the sequence of one strand, you know the sequence of the second strand

8. The two strands are complementary 9. In preparation for cell division, each strand serves as a template for a new complementary strand resulting in two copies of identical DNA 10. DNA and protein as tape measure of evolution a. DNA and protein sequences between related humans is highly similar b. If evolution is true, DNA and protein sequences between related species should also be similar c. Humans and gorillas differ in only one amino acid of hemoglobin while frogs and humans differ by 67 of the 146 amino acids