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1 MCB 3020, Spring 2005 1-10-2004 Chapter 3: The Building Blocks of Life I Chapter 3 I. The chemistry of life II. Macromolecules of the cell A. polysaccharides B. lipids C. nucleic acids D. proteins 2 The Chemistry of Life All cells are made of organic molecules. membrane lipids 3 OCH2-CH2 CH2- O-P=O O O OR C=O C=O CH2 CH2 CH2 CH2 CH2 CH2 CH2 CH2 CH2 CH2 CH2 CH2 CH2 CH2 CH2 CH2 CH2 CH2 CH2 CH2 CH2 CH2 CH2 CH2 CH2 CH2 CH2 CH2 CH3 CH3 I. The Chemistry of Life: a review A. the 6 major bioelements B. charge distribution in molecules C. attractive forces D. important functional groups 4 A. The 6 Major Bioelements C H O N P S Carbon Hydrogen Oxygen Nitrogen Phosphorus Sulfur 5 B. Charge distribution in molecules 1. electronegativity 2. hydrophilic (polar) 3. hydrophobic (nonpolar) 4. amphipathic 6 1. Electronegativity 7 A measure of the degree of attraction of valence electrons Among the major bioelements oxygen and nitrogen have the highest electronegativity TB 2. Polar (hydrophilic) 8 - + asymmetric charge distribution in a molecule d+ d- H - O - CH2 CH3 TB Polar molecules d+ d- d+ H-O-H 9 d- O H-Cd+ O Polar molecules result from the bonding of atoms with very different electronegativities TB 3. Nonpolar (hydrophobic) 10 little charge asymmetry TB Nonpolar molecules 11 hydrocarbon chain aromatic rings Nonpolar molecules result from the bonding of atoms with similar electronegativities. TB 12 4. Amphipathic partly polar, partly nonpolar phospholipid molecule negatively charged head nonpolar hydrocarbon tail TB C. Attractive forces 1. ionic bonds 2. covalent bonds 3. hydrogen bonds 4. van der Waals forces 5. hydrophobic interactions 6. comparison of bond strengths 13 1. Ionic bonds attraction between charged particles 14 NaCl + Na •••• Cl 2. Covalent bonds electron sharing between atoms •• •• H •• H H C •• H H H– C – H H 3. Hydrogen bonds (H-bonds) noncovalent bonds formed between the following: 15 1. A highly electronegative atom (usually O or N) 2. A hydrogen atom bonded to a highly electronegative atom (usually O or N) TB Hydrogen bonding of water molecules 16 H H O O H O H H H H-bonding of hydroxyl groups R O H O R H H-bonding of amino groups R R R— N N R R Keto groups R H 17 O H O R H-bonds will form with various combinations of hydroxyl, amino and keto groups that meet the H-bonding criteria. TB Hydrogen bonding between amino acids in a protein | H-C-R1 | C=O | N-H | H-C-R2 | C=O | N-H | H-C-R3 | | R4-C-H | H –N | O=C | R5-C-H | H –N | O=C | Rc- C-H | 18 19 Hydrogen bonding between bases in DNA guanine cytosine Three H-bonds between G and C 4. van der Waals forces Attraction between molecules that are very close together 20 nucleus + - + electrons induced dipoles (polar) van der Waals attractions result from attractions between induced dipoles TB 21 5. Hydrophobic forces (interactions) Attraction between hydrophobic molecules or hydrophobic portions of molecules • driven by an increase in entropy (disorder) due to water exclusion TB Water is the biological solvent of life as we know it. • cells are 70 to 90% water • water is polar • many polar biological molecules dissolve in water • nonpolar (hydrophobic) molecules tend to aggregate together in water 22 6. Comparison of bond strength type of bond 1. Covalent bonds 2. ionic bonds 3. hydrogen bonds 4. van der waals forces 5. hydrophobic forces 23 strength (kcal/mol) -50 to -100 -80 or -1 -3 to -6 -0.5 to -1 -0.5 to -3 D. Important functional groups 24 Biological importance carboxylic acid organic acids, amino and fatty acids aldehyde reducing sugars, like glucose alcohol lipids and carbohydrates Important functional groups (contd.) 25 keto pyruvate, citric acid cyle intermediates ester lipids of Bacteria and Eukarya phosphoester DNA, RNA, ATP Important functional groups (contd.) ether amino lipids (archaea) NH2 amino acids, nucleotides 26 What functional groups are present in the amino acid serine? OH CO H2N – C – H CH2OH OCO +H N – C – H 3 CH2OH serine at pH 7 27 II. Macromolecules of the cell A. polysaccharides B. lipids C. nucleic acids D. proteins 28 Monomers and polymers 29 macromolecules are polymers of covalently linked monomers monomer (eg. amino acid) covalent bond polymer (eg. protein) Macromolecules are large molecules made of repeating units (monomers). DNA a protein a nucleic acid: a chain (polymer) of nucleotides a polymer of amino acids 30 Macromolecules make up 96% of the dry weight of cells. polysaccharides proteins lipids nucleic acids 31 The 4 major cellular macromolecules*: 32 chains (polymers) of repeating units polymer monomer polysaccharide sugars example covalent bond cell wall glycosidic (see notes for other examples) lipid fatty acids or membranes ester or ether isoprenoids nucleic acid nucleotides protein amino acids enzymes *Important recurring theme DNA, RNA phosphodiester peptide B. Polysaccharides polymers of sugars linked by glycosidic bonds 1. common sugar monomers 2. glycosidic bonds 3. cellular polysaccharides 33 34 1. common sugar monomers a. glucose (ring form) b. fructose (ring form) CH2OH O OH HO HOH2C O OH OH CH2OH HO OH HO TB HOH2C 35 O c. ribose OH HO HOH2C d. deoxyribose HO O OH HO TB CH2OH O e. glucosamine HO 36 OH OH NH2 CH2OH O f. muramic acid OH HO -OOCCHCH 3 NH2 TB 2. Glycosidic bonds: a. -1,4-glycosidic bond CH2OH O CH2OH O OH H H O OH HO OH 37 OH OH 38 b. -1,4-glycosidic bond CH2OH O OH HO H OH O CH2OH O OH H OH OH 39 3. cellular polysaccharides a. starch -1,4 glycosidic bonds large polymer of glucose mostly -1,4 glycosidic bonds glucose storage molecule of plants TB 40 b. glycogen -1,6 -1,6 large branched polymer of glucose mostly -1,4 glycosidic bonds -1,6 glycosidic bonds produce branching glucose storage molecule of animals and some microorganisms TB c. cellulose 41 large glucose polymer major structural polysaccharide of plants mostly b-1,4 glycosidic bonds only microbes can break the b-1,4 bond TB d. peptidoglycan 42 large polymer of N-acetyl glucosamine and N-acetyl muramic acid the main structural component of most Bacterial cell walls b-1,4-glycosidic bonds *Penicillin inhibits Bacterial cell wall synthesis by inhibiting the formation of peptidoglycan. TB Study objectives 43 1. Memorize the 6 major bioelements. 2. Understand the terms electronegativity, hydrophilic, hydrophobic, polar, nonpolar, amphipathic. Know how these properties are important in chemical bonds and interactions. 3. Very important recurring theme: Understand the attractive forces (ionic, covalent, hydrogen bonds, van der Waals forces, and hydrophobic interactions), the examples presented in class, where they might occur. Which are strong bonds? Which are weaker? 4. Understand the role of water as the solvent of life. 5. Know the functional groups. Be able to recognize their structures. Know their biological importance and where they occur in cellular molecules. 6. Recurring theme: Know the four important cellular macromolecules (polymers), the monomers that comprise them, the bonds that connect the monomers, and the specific example presented in class. These macromolecules are the building blocks of cells. 7. In what parts of cells are the four macromolecules found? Study objectives 44 8. Describe the structure and functions of the four cellular macromolecules, the monomers, connecting bonds. Memorize the specific examples of monomers, polymers, and bonds presented in class. 9. Be able to recognize the structures of glucose, ribose, and deoxyribose. 10. Know the difference between -1,4 glycosidic bonds and b-1,4-glycosidic bonds and where they can be found. Know the features of the cellular polysaccharides presented. How does penicillin inhibit microbial growth? 8. 45 MCB 3020, Spring 2004 1-14-2004 Chapter 2 The Building Blocks of Life II: Chapter 2 (contd.) II. Macromolecules of the cell A. polysaccharides B. lipids C. nucleic acids D. proteins 46 B. Lipids 1. fatty acids (glycerol) 2. membrane lipids a. bacterial and eukaryal b. archaeal 47 B. Lipids glycerol bonded to fatty acids (or isoprenoid units) and other groups by ester or ether linkages CH2OH CHOH CH2OH glycerol O HO - C 48 1. Fatty acids a. common fatty acids palmitic (C16) stearic (C18) 49 COO COO- oleic (C18) COOa monounsaturated fatty acid TB b. saturated and unsaturated fatty acids50 saturated: no double bonds COO- monounsaturated: 1 double bond polyunsaturated: > 1 double bond COO- Unsaturated fatty acids can make the membrane more fluid. 51 52 2. Membrane lipids: glycerol phosphate bonded to fatty acids and other groups by ester or ether bonds Membrane lipids are amphipathic. polar head hydrophobic tail In aqueous solution lipids associate spontaneously to form bilayers that are the basis of biological membranes 53 The polar heads are in contact with water the nonpolar tails group with one another. a. bacterial and eukaryal membrane lipids fatty acids connected to glycerol phosphate through ester bonds 54 phosphatidic acid phosphatidyl ethanolamine phosphatidyl serine TB 55 phosphatidic acid ester bond o -o- o -ooo P o o- fatty acid TB 56 phosphatidyl ethanolamine o -o- o -o- o oP fatty acid o o- CH2CH2NH3+ ethanolamine o-CH2CH2CHCOOserine NH3+ TB b. archaeal lipids 57 isoprenoid units connected to glycerol phosphate through ether bonds ether bond -C-O-C- -O-OOH polar nonpolar TB C. Nucleic acids (DNA, RNA) polymer of nucleotides covalently linked by phosphodiester bonds DNA RNA 58 1. Nucleotides = a. Base + purines: adenine (A) guanine (G) thymine (T) (DNA only) cytosine (C) uracil (U) (RNA only) pyrimidines 59 sugar + phosphate(s) (up to 3) HOCH2 ribose (RNA) deoxyribose (DNA) OCH2 O— P=O O- Detailed picture of a nucleotide (ATP) NH2 5' phosphate end N N O -O O O -P - O - P – O - P – O- O- 60 5' O-CH2 O- OH 3' hydroxyl N O OH N adenosine triphosphate (ATP) b. phosphodiester bonds 61 5' 5' phosphate O sugars of the nucleotides are covalently linked by phosphodiester bonds 3' O base 5' H O = P - OO-CH2 O base 3' 3' hydroxyl OH H 3' 62 c. Nitrogen bases purines adenine guanine pyrimidines cytosine thymine uracil 63 Purines adenine guanine NH2 N N H N N O N N H NH N NH2 TB 64 Pyrimidines cytosine NH2 thymine O N N H uracil O NH O N H O NH N H O in RNA TB 2. DNA structure a. double-stranded helix b. sugar-phosphate backbone *sugar = deoxyribose c. nucleotide bases pair through hydrogen bonds between the helical strands d. the sequence of the bases is the "primary structure" 65 c. nucleotide base pairing The most stable complementary DNA base pairing pattern is called "WatsonCrick base pairing" where A=T and GC Two H-bonds between T and A 66 c. nucleotide base pairing guanine 67 cytosine Three H-bonds between G and C d. DNA sequence (primary structure) DNA carries genetic information in the sequence of the bases. transcription translation DNA mRNA protein 68 AAA… UUU… phenylalanine (an amino acid) 69 3. RNA structure • RNA is usually single stranded (ssRNA) • ribose instead of deoxyribose • uracil instead of thymine • primary structure = the base sequence • secondary structure = complementary base pairing in a single RNA molecule •GC A=U ssRNA intramolecular base pairing RNA stem-loop RNA secondary structure A-G-A-C-A-A-A-C-C-G-U-C-A A A A C A A- G 70 C C G U C -A RNA stem loop e.g. tRNA stem loops Functions of the major RNAs DNA 71 1. messenger RNAs (mRNA) contain mRNA genetic information to encode a protein phe 2. transfer RNAs (tRNA) act as adapters between the mRNA nucleotide code and amino acids during protein synthesis 3. ribosomal RNAs (rRNA) are structural and catalytic component of ribosomes, the protein-synthesizing machinery of cells D. Proteins 1. general structure 2. the 21 amino acids 3. peptide bonds 4. levels of protein structure 5. stereoisomers 72 D. Proteins linear chains of L-amino acids linked by peptide bonds met leu his val glu asn asp cys peptide bond e.g. enzymes, transport proteins, antibodies insulin, structural proteins, regulatory proteins, hair, flagella, viral protein coat 73 1. General structure of L-amino acids amino group -carbon O C – OH H2 N – C – H R R-group or side chain 74 carboxylic acid O C – O + H3N – C – H R at pH 7 2. The 21 amino acids encoded by DNA 75 ACIDIC aspartate glutamate BASIC lysine arginine histidine POLAR, NEUTRAL asparagine serine threonine glutamine tyrosine cysteine selenocysteine NONPOLAR (HYDROPHOBIC) phenylalanine glycine leucine alanine isoleucine tryptophan valine methionine proline Hydrophobic amino acids tend to be associated with hydrophobic environments • membranes • inside of proteins Hydrophilic amino acids are often in contact with water Lysozyme 76 a. Acidic amino acids net negative charge at pH 7 O C O + H3N - C - H CH2 COO aspartate (asp) 77 O C O + H3N - C - H CH2 CH2 COO glutamate (glu) TB b. Basic amino acids: 78 net positive charge at pH 7 CH2 CH2 CH2 CH2 NH3 + lysine (lys) CH2 CH2 CH2 + NH CH2 NH C H2N NH2 + arginine (arg) N H histidine (his) TB 79 c. Polar but neutral CH2 OH CH- CH3 OH CH2 CH2 SH OH Ser (S) Thr (T) Tyr (Y) Cys (C) TB 80 c. Polar but neutral (contd.) CH2 CH2 CH2 C O C NH2 Asn (N) O NH2 Gln (Q) CH2 SeH Sec (U) TB 81 d. Nonpolar (hydrophobic) H CH3 Gly(G) Ala (A) CH2 CH CH H3C CH3 H3C CH3 Val (V) Leu (L) CH CH3 CH2 CH3 Ile (I) TB 82 d. Nonpolar (hydrophobic) HN O C OH CH CH2 CH2 CH2 Pro (P) CH2 CH2 NH CH2 CH2 S CH3 Trp (W) Phe (F) Met (M) TB 83 Disulfide bridge covalent bond between two sulfhydryl groups (eg. of cysteines) O C O + + H3N - C - H H3N CH2 S O C - O-C-H CH2 S disulfide bridges antibody selenocysteine: the st 21 amino acid 84 O + C - OH3N - C - H CH2 SeH • found in some microbial enzymes like hydrogenase 3. Peptide bonds join L-amino acids in proteins O H C - OH H -N - C - H R2 H2 O dehydration O H C OH O peptide bond N- C-H C R2 H2N - C - H R1 O C - OH H2N - C - H R1 85 4. Levels of protein structure a. Primary (1°) structure amino acid sequence met leu his val glu asn asp cys 86 b. Secondary (2°) structure 87 Patterns of folding due to hydrogen bonds between groups of the peptide backbone -helix b-sheet 1. alpha helix (coil) CH R CH R N H CH C N R H N H CH R C CH R O O O C O O O C 88 N H CH R C N H C N H 89 2. beta sheet N N R C R C C O H N C O H N C R O C O C N C R H N R C R C C O H N C O H N C O C H C R O C R c. Tertiary (3°) structure Native 3-D structure of a protein hexokinase 90 ribonuclease Stabilized by H-bonds, hydrophobic interactions, van der Waals forces,covalent disulfide bridges, and some ionic bonds d. Quaternary (4°) structure association of two or more polypeptides -chains hemoglobin -chains 91 5. Stereoisomers Mirror-image compounds with the same molecular formula COOH H2 N - C - H CH3 L-alanine COOH H - C - NH2 CH3 D-alanine 92 Why is this important? 93 In biology, D-sugars predominate L-amino acids are found in proteins D-amino acids are less common, but are found in bacterial cell walls and antibiotics The 4 major cellular macromolecules*: 94 chains (polymers) of repeating units polymer monomer polysaccharide sugars example covalent bond cell wall glycosidic (see notes for other examples) lipid fatty acids or membranes ester or ether isoprenoids nucleic acid nucleotides protein amino acids enzymes *Important recurring theme DNA, RNA phosphodiester peptide Study objectives 95 1. Contrast saturated and unsaturated fatty acids. Understand how and why they influence membrane fluidity. Know the general structure of membrane lipids. Know the names of the fatty acids and lipids presented in class. You do NOT need to memorize the structure of the individual fatty acids, ethanolamine, or serine. 2. Compare and contrast bacterial,eukaryal, and archaeal lipids, especially the molecular components and the bonds. More details later. 3. What are nucleic acids? Understand that nucleotides are composed of a nitrogenous base (purine or pyrimidine), a sugar (ribose or deoxyribose), and one to three phosphates. Know the structure of the phosphodiester bond. What parts of the nucleotides are connected by the phosphate of the phosphodiester bond? What is meant by the 5' and 3' ends of DNA and RNA? 4. Memorize the structure of the nucleotide ATP. This is a very important molecule and we will discuss it in great detail throughout the semester. 5. Know the purines and pyrimidines. Know the number of rings in each. What is the structural difference between thymine (T) and uracil (U)?