BIO291 Fall 2023 Macromolecules PDF

9/8/23 BIO291 - Fall 2023 Macromolecules Instructor: Prof. P. DiMarzio 1 1 Macromolecules – Four main types: • Carbohydrates • Lipids • Proteins • Nucleic acids – Monomers: subunits of macromolecules – Polymers: chains of various lengths of monomers Instructor: Prof. P. DiMarzio 2 2 1 9/...

9/8/23 BIO291 - Fall 2023 Macromolecules Instructor: Prof. P. DiMarzio 1 1 Macromolecules – Four main types: • Carbohydrates • Lipids • Proteins • Nucleic acids – Monomers: subunits of macromolecules – Polymers: chains of various lengths of monomers Instructor: Prof. P. DiMarzio 2 2 1 9/8/23 Carbohydrates • Large and diverse group that include sugars and starches • Serve as cell structures and cellular energy sources • Consist of C, H, and O • Classified in – Monosaccharide – Disaccharides – Polysaccharides 3 Instructor: Prof. P. DiMarzio 3 Monosaccharides Classified based on the position of their: carbonyl group 1. carbonyl group 2. number of carbons in the backbone Aldoses have a carbonyl group at the end of the carbon chain; attached to a C and H (aldehydes) ketoses have a carbonyl group in the middle of the carbon chain; attached to a 2 C (ketones) 4 https://courses.lumenlearning.com/bio1/chapter/reading-types-of-carbohydrates/ 4 2 9/8/23 Monosaccharides • Simple sugars with 3-7carbon atoms containing a single aldehyde or ketone à functional group (Aldoses and ketoses) • Number of carbons: trioses, tetroses, pentoses Hexoses, and heptoses, etc. - Ribose (RNA) and Deoxyribose (DNA) – pentose - Glucose (main energy supply) - hexose Glucose and fructose: • have the same formula: C6H12O6 • together form the disaccharide sucrose 5 Instructor: Prof. P. DiMarzio 5 Disaccharides • Formed when two monosaccharides are joined in a process called dehydration synthesis (glycosidic bond) with production of water • Disaccharides are broken down by hydrolysis (water is used to break down a compound) • Some Important disaccharides: - Sucrose - table sugar (1 glucose + 1 fructose) - Lactose - milk sugar (1 glucose + 1 galactose) dehydration synthesis - Maltose – found in molasses (2 glucose molecules) Instructor: Prof. P. DiMarzio a 1-4 glycosidic bond 6 6 3 9/8/23 Polysaccharides • Complex carbohydrates built from monosaccharides to form large polymers • Used by both plants and animals to store glucose – starch and glycogen • Provide some of the mechanical structure of cells – Chitin: cell wall found in fungi and exoskeleton of arthropods (ex. crayfish) – Peptidoglycan: component of the bacterial cell wall – Cellulose: plant cell wall Glycogen granules (branched) in muscle Starch granules in potato tuber cells tissue Instructor: Prof. P. DiMarzio Starch is a mixture of two polymers: amylose (linear) and amylopectin (branched). 7 Glycogen • is the energy reserve carbohydrate of animals • is highly branched (8–12 glucose units between branches) • Practically all mammalian cells contain some stored carbohydrates in the form of glycogen, but it is abundant in the liver (4%–8% by weight of tissue) and in skeletal muscle cells (0.5%–1.0% by weight of tissue) Instructor: Prof. P. DiMarzio Glycogen contains in its core a glycogenin (enzyme that converts glucose to glycogen) https://en.wikipedia.org/wiki/Glycogen 8 8 4 9/8/23 Starch • Starch is a mixture of two polymers: • amylose (linear) usually 20-30%; can rang from 1% to 70 in high amylose starches • amylopectin (branched) usually 7080% Amylose • The Iodine test is used to detect starch in a sample • The characteristic blue-violet color that appears when starch is treated with iodine is due to the formation of the amylose-iodine complex. • The helical structure of amylopectin is disrupted by the branching of the chain, so amylopectin in the presence of iodine produces reddish brown color. Amylopectin https://chem.libretexts.org/Courses/Sacramento_City_College/SCC%3A_Chem_309__General_Organic_and_Biochemistry_(Bennett)/Text/14%3A_Carbohydrates/14.7%3A_Polysaccharides 9 Cellulose Cellulose microfibrils in a plant cell wall Cellulose • Linear polymer of glucose that can pack closely into fibers Molecules • Cannot be broken by any enzyme produced by animals • Constitutes the fiber part of food • Some microorganisms can digest cellulose (enzyme cellulase, which catalyzes the hydrolysis of cellulose) • These microorganisms are present in the digestive tracts of herbivorous mammals (such as cows, horses, and sheep) and insects, such as the termites Rumen Grass Cellulose Glucose Microbial fermentation Fatty acids (Nutrition for animal) CO2 + CH4 (Waste products) 10 10 5 9/8/23 Lipids • Greek work lipos which means ‘fat’ • Primary components of cell membranes and essential to their function • Consist of C, H, and O • Are non-polar (no positive and negative ends) and insoluble in water (hydrophobic) • Dissolve in organic solvents (chloroform, ether, or acetone) - Simple Lipids - Complex Lipids - Steroids Instructor: Prof. P. DiMarzio 11 11 Simple Lipids • Simple lipids à esters of fatty acids and glycerols or alcohols. • There are two types of simple lipids – fats/oils à fatty acids (C4-C24) and glycerol – Waxes à long chains of fatty acids (C14-C36) and alcohols (C16-C30) Instructor: Prof. P. DiMarzio 12 12 6 9/8/23 Simple Lipids: fats/oils • Triglycerides (alias fats) made of glycerol and 3 fatty acids are the most abundant lipids in living organisms -Glycerol 3-C molecule with 3 hydroxyl groups (OH) -Fatty acids consist of long hydrocarbon chain ending in carboxyl group 13 Instructor: Prof. P. DiMarzio 13 Simple Lipids • Fatty acids can be: • Saturated fat (no double bonds in the fatty acids) • Unsaturated fat (one double bond in the fatty acids; H atoms can be added) • Polyunsaturated fat (at least 2 double bonds) • In food lipids are found in the form of triglycerides Instructor: Prof. P. DiMarzio 14 14 7 9/8/23 Cis- and Trans- unsaturated fatty acids • Naturally occurring fatty acids occur in cis configuration; the chain is bent (the molecule is bent at each double bond) • A trans unsaturated fat has a straight chain; rare in nature, can be made by a process called hydrogenation • Hydrogenation converts double bonds to single bonds or from cis to trans configuration • the resulting molecule is solid at room temperature and has a long shelf life (ex. Shortening or margarine) Instructor: Prof. P. DiMarzio 15 15 OMEGA-3 fatty acids • Two main omega-3 fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are found mainly in fish and fish oil • Omega-3s from fish and fish oil have been recommended by the American Heart Association (AHA) to reduce cardiovascular events Instructor: Prof. P. DiMarzio 16 https://www.eufic.org/en/whats-in-food/article/the-importance-of-omega-3-and-omega-6-fatty-acids 16 8 9/8/23 Complex Lipids • Contain C, H, and O + P, N, and/or S • Cell membranes are made of complex lipids called phospholipids – Glycerol, two fatty acids, and a phosphate group • Phospholipids have polar as well as nonpolar regions • Glycolipids • Cholesterol • Fat-soluble vitamins Instructor: Prof. P. DiMarzio 17 17 2.7 | Lipids (5 of 5) The phospholipid phosphatidylcholine § A phospholipid molecule resembles a fat, but has only two fatty acid chains § The third hydroxyl group of glycerol is bonded to a phosphate group with attached variable group X Copyright ©2020 John Wiley & Sons, Inc. 18 9 9/8/23 • Phospholipids are the main molecules that make up the lipid bilayer in biological membranes 19 Instructor: Prof. P. DiMarzio 90 CHAPTER 3 | BIOLOGICAL MACROMOLECULES 19 Steroids Unlike the phospholipids and fats discussed earlier, have a fused ring structure. Although they do not resemble the other lipids, they are grouped with them because they are also hydrophobicand insoluble in water. All steroids have four linked carbon rings and several of them, like cholesterol, have a short tail ( ). Many steroids also have the –OH functional group, which puts them in the alcohol classification (sterols). Steroids • Cholesterol • Reinforces the cell membrane in animal cells but it is absent in the cell Steroids vary in the functional groups membrane of bacteria attached to the set of 4 carbon rings • Synthesized in the liver, it is the precursor to many steroid hormones: • Estrogen • Progesterone • Testosterone Figure 3.21 Steroids such as cholesterol and cortisol are composed of four fused hydrocarbon rings. • Cortisol 20 Cholesterol is the most common steroid. Cholesterol is mainly synthesized in the liver and is the precursor to many steroid hormones such as testosterone and estradiol, which are secreted by the gonads and endocrine glands. It is also the precursor to Vitamin D. Cholesterol is also the precursor of bile salts, 20 which help in the emulsification of fats and their subsequent absorption by cells. Although cholesterol is often spoken of in negative terms by lay people, it is necessary for proper functioning of the body. It is a component of the plasma membrane of animal cells and is found within the phospholipid bilayer. Being the outermost structure in animal cells, the plasma membrane is responsible for the transport of materials and cellular recognition and it is involved in cell-to-cell communication. 10 9/8/23 Proteins • Made of C, H, O, N, and S • Most abundant organic molecules in living systems (50% of the dry weight of cells) • Essential in carrying out cell’s activities – accelerate reactions (enzymes) – mechanical support (structural protein) – regulatory functions (hormones) – specific response to stimuli (receptors) – biological movements (contractile filaments and molecular motors) Instructor: Prof. P. DiMarzio 21 21 Amino Acids • Monomers that make up protein • Each amino acid has the same fundamental structure: - An alpha-carbon with attached: • Carboxyl group (–COOH) • Amino group (–NH 2) • Side group Instructor: Prof. P. DiMarzio 22 22 11 9/8/23 2.7 | Building Blocks of Proteins The Structure of Amino Acids § Proteins are unique polymers made of amino acid monomers. § Twenty different amino acids, with different chemical properties, are commonly used in the construction of proteins. § All amino acids have a carboxyl and an amino group, separated by a single carbon atom, the α-carbon. § The a-carboxyl of one amino acid is linked to aamino group of another by a condensation (dehydration) reactions (peptide bond) 23 Proteins: Peptide Bonds • Amino acids in a polypeptide are termed residues; residue on the N-terminus contains free a-amino group while the C-terminus has a free a-carboxyl group. http://www.bioinfo.org.cn/book/biochemistry/chapt05/bio3.htm 24 24 12 9/8/23 The 20 Amino acids - hydrophilic - hydrophilic 25 25 The 20 Amino acids - hydrophobic 26 26 13 9/8/23 2.7 | Building Blocks of Proteins (4 of 5) The Properties of the Side Chains § Disulfide bridges often form between two cysteines that are distant from one another in the polypeptide backbone or even in two separate polypeptides. § Disulfide bridges help stabilize the shapes of proteins. Formation of disulfide bonds: oxidation and reduction of bonds between two cysteine residues Copyright ©2020 John Wiley & Sons, Inc. 27 • Peptide: a molecule composed of short chains of amino acids • Polypeptide: usually has > 20 amino acids and is smaller subunit of a protein • Protein: usually contains a minimum of 50 amino acids Instructor: Prof. P. DiMarzio 28 28 14 9/8/23 Levels of Protein Structure • A functional protein is one or more polypeptide chains precisely twisted, folded, and coiled into a molecule of unique shape • The shape of a protein is critical to its function • Four levels of protein structure - Primary - Secondary - Tertiary - Quaternary Instructor: Prof. P. DiMarzio 29 29 Primary and Secondary Structures • Primary - The unique sequence of amino acids in a polypeptide chain • Secondary - The folding of the polypeptide chain into helices and sheets held in shape by hydrogen bonds between carbonyl and amino groups in the peptide backbone Instructor: Prof. P. DiMarzio 30 30 15 9/8/23 Tertiary and Quaternary Structures • Tertiary - The unique three-dimensional structure of a polypeptide - Determined by a variety of chemical interactions (ionic, hydrogen, and disulfide bonds) • Quaternary - Interaction of multiple polypeptides (known as subunits) to form one functional protein The threedimensional structure of myoglobin Hemoglobin 31 Instructor: Prof. P. DiMarzio 31 Denaturation and Protein Folding • The native state of a protein is the functional three-dimensional form • The information that governs folding is embedded in the amino acidic sequence of the protein • When a protein encounters extreme conditions, it may unfold or “denature” - Extreme temperature, pH, salt concentration, organic solvents A denatured protein has no shape, thus no activity 32 32 16 9/8/23 Protein folding alternative pathways: 1st pathway The information that governs folding is embedded in the amino acidic sequence of the protein Folding a helices and b sheet 1st pathway: • First, formation of the a helices and b sheets • Second, the protein folds due to the hydrophobic interactions (nonpolar residues move to the center of the protein) 33 33 Protein folding: 3 alternative pathways: 2nd and 3 rd pathway Folding a helices and b sheet 2nd pathway: • First, the protein folds by hydrophobic interaction • Second, the secondary structures a and b sheet forms 3rd pathway: • secondary structure formation and compaction occur simultaneously 34 17 9/8/23 Molecular Chaperones • Help proteins to fold into final 3D conformation • Chaperons bind to stretches of hydrophobic amino acids in the linear protein (primary structure) • Chaperones prevent forming polypeptides from binding to other proteins in the cytosol preventing misfolding or aggregation • The final polypeptide is then released by the chaperones and spontaneously fold into the final protein • The forming protein can fold inside a chaperon named chaperonin (TRiC) 35 35 Nucleic Acids • Named because they are acids found in the nucleus! • The most important macromolecules for the continuity of life • Two types: - DNA (Deoxyribonucleic acid) • the repository of genetic information - RNA (Ribonucleic acid) • the expression of genetic information Instructor: Prof. P. DiMarzio 36 36 18 9/8/23 Nucleotides • Nucleic acids are polymers made from monomers called nucleotides Nitrogenous base (can be A, G, C, or T) • Each nucleotide has 3 parts: 1. a five-carbon sugar 2. a phosphate group 3. a nitrogencontaining base Phosphate group Phosphate Base Sugar Sugar Instructor: Prof. P. DiMarzio 37 37 Components of the Nucleic Acids • Nucleotide (monomer of nucleic acids) 1.Pentose sugar (DNA: deoxyribose; RNA: ribose) 2.Nitrogenous Base 3.Phosphate (PO43-) Nitrogenous bases Pyrimidine bases Purine bases (a single six-membered heterocyclic ring) (two fused heterocyclic rings) Cytosine (C) Thymine (T) Uracil (U) Adenine (A) Guanine (G) 38 38 19 9/8/23 Backbone of DNA chain 5¢ position • Alternating phosphates and the pentose sugar deoxyribose 3¢ position • Phosphates connect 3ʹ-carbon of one sugar to 5ʹ-carbon of the adjacent sugar by an ester linkage: phosphodiester bond Deoxyribose Phosphodiester bond 39 39 The Double Helix 3¢-Hydroxyl 5¢-Phosphate Hydrogen bonds Phosphodiester bond 5¢-Phosphate • All cells have DNA in double- stranded molecule • Two strands: - Held together by hydrogen bonds between the bases - Have complementary base sequences • Adenine - Thymine • Guanine - Cytosine - are antiparallel - wrapped around each other to form a double helix 3¢-Hydroxyl 40 40 20 9/8/23 The Double Helix • A single strand of nucleotides has no helical structure • The helical shape of DNA depends entirely on the pairing and stacking of bases in the antiparallel strands taL75225_ch08_216-251.indd Page 228 5/10/08 7:11:17 PM user-s174 228 Chapter 8 /Volumes/MHDQ/MH-DUBUQUE/MHDQ024/MHDQ024-08 An Introduction to Microbial Metabolism NAD! A NOTE ABOUT ELECTRON AND PROTON CARRIERS: MOLECULAR SHUTTLES Carrier molecules resemble shuttles that are alternately loaded and unloaded, repeatedly accepting and releasing electrons and hydrogens to facilitate the transfer of redox energy. The most common carrier is the coenzyme nicotinamide adenine dinucleotide (NAD1), which carries hydrogens and a pair of electrons (figure 8.13). Other common redox carriers are FAD, NADP (NAD phosphate), coenzyme A, and the compounds of the respiratory chain, which are fixed into membranes. A molecule such as NAD1 carries the electrons between substrates. During catabolic reactions discussed in section 8.3, some energy given off by electron transfer is used to synthesize ATP. To complete the reaction, the electrons are passed to a final electron acceptor. In aerobic metabolism, this acceptor is molecular oxygen; in anaerobic metabolism, it is some other inorganic or organic compound. NADH H From substrate Oxidized nicotinamide Reduced nicotinamide H H H+ C C C NH2 C H C C C N C C C O 2H 2e: NH2 C N C O Stacking:P adds stability by excluding water P P 41 P 41 Substrate I (Red) NAD! (Ox) NAD Final electron acceptor (Red) Adenine Ribose ATP Substrate I (Ox) Adenosine Triphosphate (ATP) Figure 8.13 NADH (Red) NAD H Reduced NAD1 can be represented in various ways. Because 2 hydrogens are removed, the actual carrier state is NADH 1 H1, but this is somewhat cumbersome, so we will represent it with the shorter NADH. With the transfer process being cyclic, there is a built-in efficiency. Oxidized NAD1 is automatically regenerated and can be ready to accept more electrons. Details of NAD reduction. The coenzyme NAD1 contains the vitamin nicotinamide (niacin) and the purine adenine attached to double ribose phosphate molecules (a dinucleotide). The principal site of action is on the nicotinamide (boxed area). Hydrogens and electrons donated by a substrate interact with a carbon on the top of the ring. One hydrogen bonds there, carrying two electrons (H:), and the other hydrogen is carried in solution as H1 (a proton). The most important energy storage in the cell H H N N Adenosine Triphosphate: Metabolic Money ATP has been described as metabolic currency because it can be earned, banked, saved, spent, and exchanged. As a temporary energy repository, ATP provides a connection between energy-yielding catabolism and all other cellular activities that require energy. Some clues to its energy-storing properties lie in its unique molecular structure. The Molecular Structure of ATP ATP is a three-part molecule consisting of a nitrogen base (adenine) linked to a 5-carbon sugar (ribose), with a chain of three phosphate groups bonded to the ribose (figure 8.14). The type, arrangement, and especially the proximity of atoms in ATP combine to form a compatible but unstable high-energy molecule. The high energy of ATP originates in the orientation of the phosphate groups, which are relatively bulky and carry negative charges. The proximity of these repelling electrostatic charges imposes a strain that is most acute on the bonds between the last two phosphate groups. When the strain on the phosphate bonds is released by removal of the terminal phosphates, free energy is released. OH HO P O OH O P O OH O P H O C Adenine N N N H O O Ribose H H H H OH OH ATP is a three-part molecule • Adenine • Ribose • Three phosphate groups Adenosine monophosphate (AMP) Adenosine diphosphate (ADP) Adenosine triphosphate (ATP) Bond that releases energy when broken Figure 8.14 The structure of adenosine triphosphate (ATP) and its partner compounds, ADP and AMP. Instructor: Prof. P. DiMarzio 42 42 21 9/8/23 DNA: the Architectural Blueprint for Life • DNA contains information written in a genetic code • The sequence of nucleotides constitutes the code • RNA transfers the information from DNA to proteins • Central Dogma of Molecular Biology - DNA RNA Proteins • DNA is organized in genes and chromosomes Image credit: Genome Research Limited 43 22