Making and Breaking Macromolecules

1. Making and Breaking Macromolecules O– H+ O P O NH2 H+ O– C N C N A HC C C N N R H H O H N C C OH H CH2 O OH H Polymer: macromolecule made of many identical/similar units bound together Monomer: individual unit (building blocks) of a polymer Polymer Monomers Covalent Bonds joining Monomers together Examples of Monomers = = Nucleotide Amino Acid

2. Why Carbon? • Organic Chemistry: Study of the carbon-based molecules that are involved in the majority of life processes and structures. • Macromolecule: very large molecule with dozens or even thousands of atoms; Usually based on long chains or rings of carbon atoms • Diversity in organic molecules comes from: • Number and arrangement of Carbon atoms (chains, rings, branches; determines basic structure) • Functional Groups: Interchangeable groups of molecules that have distinct properties (e.g. Polar vs. Non-Polar) – determine the behavior of the macromolecule. Phenyl functional Group O H H H δ + C C C C C C C C OH N NH3 Carboxylic Acid Functional Group H H H O δ – Amino functional group

3. The 4 Classes of Organic Molecules • Nucleic Acids • Relatively Simple structure • Contains all the information for making proteins, and in turn organisms • Proteins • Highly Diverse Functions • Major building material for making cells/bodies • Molecular machine doing most of the work required to sustain life. • Carbohydrates • Sugars and Starches • Energy Molecules • Lipids • Fats and Oils • Membranes and Energy

4. NUCLEIC ACIDS Molecular Building Blocks of Life Water Nucleic Acids Proteins Lipids Carbohydrates Organic Molecules

5. Nucleic Acids HN H O– O– O– O– H+ H+ H+ H+ C CH N O O O O P P P P O O O O C NH2 CH C O H+ H+ H+ H+ O– O– O– O– C N N C N Thymine A HC O C C N N H C H N H3C C T C CH N O Cytosine T A Guanine 3’ G C O A T C N C N H G HC A T C C N N N H H CH2 CH2 CH2 CH2 T O O O O A C G OH OH OH OH H H H H 5’ Purines Pyramidines • Nucleotide: Monomer of nucleic acids • Ribose (5-sugar) “Backbone” • Phosphate group (acidic) • Nitrogen containing Base Group (i.e. not an acid) determines the identity of the nucleotide • Covalent bonds between the sugar and phosphate group link adjacent nucleotides • Deoxyribonucleic acid (DNA) • Two joined strands form a “Ladder” • Bases on opposite side of the ladder are bound by hydrogen bonds. • ComplementarityA bind with T and G binds with C (knowing the base sequence on one strand determines the sequence on the second strand) • Anti-parallel: one strand is upside down relative to the other • Double Helix: structure of DNA resulting from twisting the ladder • The sequence of A, T, C, and G on one strand contains the coded information for making RNA/Protein. Adenine 5’ DNA DNA Double Helix 3’

6. Hydrogen Bonding in DNA (FYI) O H C N H3C C T C CH N O H HN O– C N C N A HC O P O C C N N H H OH CH2 H+ O– O O O– H+ CH2 H O P O O– H O H NH H C N C O– C N G CH N HC C O O– H+ C C CH2 H O P O N CH C O N N N O P O H+ O– H O– O O– P O H+ CH2 O H+ O– OH H

7. Central Dogma The “Central Dogma” of Biology is: Transcription Translation RNA Protein DNA DNA: DNA’s only function is to be read like a book for the information it stores. RNA: One type of RNA is made by copying a part of the nucleotide sequence found in DNA – it functions as a messenger with the information. Other type of RNA act as enzymes, or regulate cell functions. Proteins: Proteins are the work horses doing most of the work in a cell, and providing much of the structure.

8. Ribonucleic Acids (RNA) A HN H O– O– O– O– H+ H+ H+ H+ C H3C C CH N O O O O P P P P O O O O C A NH2 CH C O H+ H+ H+ H+ O– O– O– O– C N N C N Thymine A HC O C C O Uricil N N H H+ C O– C H N H3C C C O H T N H3C C U P C CH O C N O H+ N CH2 O O– O U U OH H Cytosine Guanine G OH O C N OH C N H G HC C C N N OH N H H CH2 CH2 CH2 CH2 O O O O OH OH OH OH OH OH H H H H OH Purines Pyramidines • RNA differs from DNA: • RNA has the same nucleotides but replaces Thymine with Uricil. • RNA replaces and “H” with an “OH” on ones of its sugar’s carbons • RNA almost always remains single stranded • Can fold and behave like enzymes • Different types of RNA • mRNA (messenger RNA) sequence of nucleotides is read to determine amino acid sequence during translation. • tRNA (transfer RNA) “cipher” which converts mRNA codon sequence to an amino acid. • rRNA (ribosomal RNA) major component of Ribosomes, which carry out translation. • Some small RNAs help regulate gene expression • ATP, (also GTP etc.) provide chemical energy to fuel many reactions. OH OH Adenine OH OH mRNA tRNA

9. ATP O O C O C H C H H O O NH2 P P O– O– H+ H+ C ATP N O2 C N A H+ H+ O– O– O HC C O CO2 C O C C H C H N H N ATP H H2O CH2 O OH OH • Single RNA nucleotide: Adenine • High Energy Phosphate Groups • Job of Cellular Respiration is to add inorganic phosphate (Pi) groups to form Adenosine Tri Phosphate (ATP) • Last phosphate group releases energy when broken • Can be transferred to enzymes or other molecules to activate • Becomes ADP after loss • Other nucleotides can also be used for high energy molecules (i.e. GTP) ATP produced as energy is captured via Cellular Respiration O P O H+ O H+ H+ O O – – – H+ O– Adenosine Tri Phosphate (ATP) Adenosine Mono Phosphate (AMP) Adenosine Di Phosphate (ADP) Inorganic Phosphate (Pi) Inorganic Phosphate (Pi) H2O 2

10. Using ATP to do work O NH2 O P O– H+ H+ – C N C N A H+ O– HC O O C C N N H P O H+ O O P – H+ O– H+ O– CH2 O OH OH • The energy from an Exergonic Reaction can be used to carry out an Endergonic Reaction • ATP (Adenosine Tri-Phosphate) • Molecule with a very high energy bond (the last phosphate group) • ATP Hydrolysis: • breaking the bond binding the last phosphate group to ATP to release energy • ATP  ADP + Pi + Energy • Coupled Reactions • Alone, hydrolyzing ATP would only release heat/light energy • Enzymes can couple the reactions to capture this energy and get an Endergonic Reaction to occur. H2O Energy Adenosine Tri Phosphate (ATP) Pi = Inorganic Phosphate Group Adenosine Di Phosphate (ADP) EA ATP P EA With a catalyst Energy Energy With a catalyst ADP + P R Exergonic Endergonic Time Time

11. Amino Acids (aa) H H O H H H N C C R R H H O N C C H H O H H O OH N C C N C C R R Peptide Bond • Amino Acid (aa): Monomer of Proteins • “N – C – C” Backbone with Hydrogens and an Oxygen • “R” = functional groups • Only 20 kinds used in proteins • Made of H, C, and sometimes O, N, and/or P • Different properties (see chart) • New Amino acids can be joined ad-infinitum through dehydration synthesis joining Amino-end of one aa to the Carboxy end of an existing polypeptide. • Polypeptide: chains of amino acids joined together Amino End(N-terminus) Carboxyl end(C-terminus) OH OH

12. Protein Folding and Function H H O H H O H H O . . . . . . N C C N C C N C C R R R • Proteins are made of amino acids linked together in a chain. • The chain folds on itself into a functional shape. • Shape of the protein once it is folded up determines its function. • Proteins with a different order and combination of amino acids fold differently Hydrophilic Amino Acids Hydrophobic Amino Acids Chain of thousands of amino acids Different Proteins have different shapes; the shape determines the function of the protein.

13. Mechanism of Action of Enzymes Regulatory Site • Enzymes: Organic Catalyst; increase rate of chemical reaction without being used up or altered by the reaction; can be used over and over again. • Hold substrates in “intermediate state” thus reducing the activation energy • Active Sites bind Reactants (substrates); Shape determines their function • Can mediate Endergonic reactions by coupling the reaction to ATP Hydrolysis and phosphorylation of the protein (the Phosphate group alters the way amino acids interact and thus the protein conformation) • Coenzymes (vitamins) are often needed to facilitate an enzymes activity • Regulating Enzymes • Negative Feedback: frequently the product of the reaction binds to a separate site on the protein preventing any further activity; ensures that the proper level of products are made. • Competitive Binding (Inhibition): sometimes molecules similar in shape to a reactant can bind to the active site, blocking it from activity ATP Active Site Coenzyme ADP Pi Enzyme Mechanism of Action: Description of the physical interactions that bring about specific effects. P EA With a catalyst Energy R Without an enzyme the Activation energy is very high Enzymes lower the Activation energy by reducing the energy of the intermediate state, thus speeding up the reaction. Energy Endergonic Time

14. Types of Proteins Cytoskeletal Proteins Collagen • Fibrous Proteins • Minimal folding forms long strands. • Usually serve as structural proteins • Cellular Cytoskeleton (inside the cell) • Extracellular matrix: Collagen, Elastin and Reticular fibers • Globular Proteins: • Fold extensively to form odd shaped globs often with moving, functional parts, like machines • Integral Proteins • Receptors • Transport Proteins • Cell-Cell Adhesion proteins (CAMs) • “ID” proteins • Note: the transmembrane portion of integral proteins is hydrophobic, while the rest is hydrophilic • Signaling Molecules • First messengers such as hormones • Enzymes in Signal Cascades • Cytosolic and Blood born enzymes (molecular machines; e.g. RNA Polymerase, Lactase) • Histones: DNA Packaging protein • Transcription Factors Signaling Molecule Transport Protein “ID” Protein Receptor Adhesion Protein Messenger Transcription Factor Enzyme Histones

15. Carbohydrates H H OH C C C O C OH OH H C C C OH H H H C C C C OH H C CH2OH CH2OH CH2OH CH2OH O O O O HO OH HO OH HO O OH OH OH OH OH H H H H H H OH OH OH OH H OH • Monosacharide (monomer) • Structure • Hydrated (Watered) Carbon Chains; Usually have the ratio CH2O • If the chain is long enough, the ends usually connect to make a ring (not by dehydration) • Examples • Glucose: 6-carbons; blood sugar • Pentose: 5-carbons sugar; in Nucleic Acids • Glycerol: modified 3-carbon sugar-alcohol found in lipids • Disaccharide • Two monosaccharides join by dehydration • Poly-Saccharide • Glycogen: Poly-glucose used for storage in animal cells • Starch: Poly-glucose used for storage in plant cells (not as branched); table sugar • Cellulose: Poly-glucose molecule with alternating directions of linkage, used for structure in plants. Roughage in animal diets. H O H H OH H OH H OH H OH H OH Glucose

16. Some Common Carbohydrates OHCH2 OH O H HO CH2OH H OH H Fructose CH2OH H H H CH2OH CH2OH CH2OH CH2OH O O H HO OH OH H H H HO H O O H H H H H H O OH H H OH OH H H OH H O Glucose H H HO OH OH OH OH H OH H Glucose Galactose CH2OH OH OH CH2OH H H Glucose Glucose O Lactose(Milk Sugar) HO OH H OHCH2 H H H OH Maltose(Grain Sugar) O H H OH H H HO OH H HO O CH2OH OH OH H H OH H Galactose Glucose Fructose Sucrose(Table (Fruit) Sugar) Polysacharides are composed of many monosaccharides bound together O O Glycogen: Animal carbohydrate storage Starch: Plant carbohydrate storage Cellulose: Plant based structural molecule (Cell Wall) Disaccharides are composed of two sugars bound together Highly branched Moderately branched Unbranched Monosaccharides are comprised of single sugars, usually as rings

17. Polysacharides Branching patterns 6 6 CH2OH CH2OH 5 5 O O Moderately branched H H H H H 4 1 H H OH OH 1 4 O O 3 2 3 2 H OH H HO O 6 Starch CH2OH CH2 CH2OH CH2OH O O O O H H H H H H H H H H H H H H H H OH OH OH OH O O O O O H H H H OH OH OH OH 6 6 CH2OH CH2OH 5 5 Highly branched O O H H H H H 4 1 H H OH OH 1 4 O O 3 2 3 2 H OH H HO O 6 CH2OH CH2 Glycogen O O H H H H H H H H OH OH HO O H H OH HO O CH2 CH2OH CH2OH O O O H H H H H H H H H H H H OH OH OH O O O O Unbranched H H OH H HO OH Cellulose 6 CH2OH CH2OH OH OH H H 5 3 2 O O H H H H O O 1 4 4 H OH H OH H H H H OH H OH H 1 O O O H H H H O O 3 2 5 OH OH H H CH OH CH OH 2 2 6

18. Energy for Life Glucose Oxygen O O C C O O O O O O H H H H Adenosine Tri Phosphate (ATP) CarbonDioxide CarbonDioxide Water Water Chloroplast Mitochondria Sun Energy+ 6H20 + 6CO2 C6H12O6 + 6O2 6CO2 +6H20 + ATP (~38) Photosynthesis Respiration • Carbohydrates are central to the energy flow required for most life • Simple sugars are made by photosynthesis • These sugars are used: • As starting material for other organic molecules • As energy storage molecules

19. LIPIDS Molecular Building Blocks of Life Water Nucleic Acids Proteins Lipids Carbohydrates Organic Molecules

20. Lipids O O C C CH2 CH2 CH2 CH2 CH2 CH2 CH2 CH2 CH2 CH2 CH2 CH2 CH3 CH3 Glycerol Fatty Acid Chains CH3 O O C C CH2 CH2 CH2 CH2 CH2 CH2 CH2 CH2 CH2 CH2 CH2 CH2 CH3 CH3 H2C O CH3 CH3 O O C C CH2 CH2 CH2 CH2 CH2 CH2 CH2 CH2 CH2 CH2 CH2 CH2 CH3 CH3 HC O CH3 CH3 Glycerol H2C O O OH O HC P O CH2 CH2 O CH3 CH3 O– N+ H2C O CH3 O Some Eicosanoids Cholesterol O H+ O P O CH2 CH2 – Phospholipid C CH2 CH2 CH2 CH CH CH2 CH3 CH3 CH3 O– N+ CH3 Prostaglandin Leukotriene E4 Triglyceride • Long Chains of Hydrocarbons (Carbons and Hydrogens) with a few Oxygen Atoms. • Insoluble in Water • Triglycerides (Solid=fat, Liquid=oil) • Glycerol backbone: Modified simple sugar with three carbons • Fatty Acid Chain: Carbonic Acid at one end of a long hydrocarbon chain • Saturated means it has as many hydrogens as possible (solid at room temp, like butter) • Unsaturated means that in place of pairs of hydrogens, Carbons share double or triple bonds, kinking the chain (liquids at room temp, like oil) • Phospholipids • Replace one fatty acid chai with a Phosphorous containing group: hydrophilic “head” • Amphipathic: molecule with hydrophobic and hydrophilic regions • Basic component of all membranes • Steroids • Four interlocking hydrocarbon rings • Cholesterol is modified to form all other steroids in your body (testosterone, estrogen, progesterone, aldosterone etc) as well as Vitamin D and Bile Salts. • Eicosanoids • Diverse group of 20-carbon fatty acid chains • Blood clotting , inflammation and labor contractions, etc. 3H2O Fatty Acid Chains H HO H HO H HO Triglyceride Phosphate Head CH2 H2C O OH

21. Saturated vs. Unsaturated Fatty Acids O CH2 CH2 CH2 CH2 CH2 CH2 CH2 CH2 CH2 CH2 CH2 CH2 CH2 CH2 CH2 CH2 CH3 C HO Saturated fatty acid (Stearic acid) O C CH CH2 CH2 CH2 CH2 CH2 CH2 CH2 HO CH CH2 CH CH CH2 CH2 CH2 CH2 CH3 Unsaturated fatty acid (Linoleic acid)

22. Membranes CH3 CH3 CH3 CH3 CH3 Hydrophilic (water loving) Integral Protein CH3 CH3 CH3 CH3 CH3 CH3 CH3 CH3 CH3 CH3 CH3 CH3 CH3 CH3 CH3 CH3 CH3 CH3 CH3 CH3 OH OH OH OH OH Hydrophobic(water fearing) • The heads of phospholipids are Hydrophilic • The tails of phospholipids are Hydrophobic • Phospholipids line up with their heads next to each other and their tails next to each other • Phosphlipid Bilayer: structure of organic membranes comprised of two layers of Phospholipids lined up with their tails facing each other, so that they don’t have to “see” the water. • “Membranes” like this form spontaneously in water similarly to soap bubbles but are very fragile • Integral Proteins, and Cholesterol (animals) or Phytosterol (plants) molecules mix in with cellular membranes to strengthen them and add functionality. • Carbohydrate groups are bound to some proteins and phospholipid heads.

23. Phospholipid Bilayers O C CH2 CH2 CH2 CH2 CH2 CH2 CH3 Fatty Acid Chains Glycerol O C CH2 CH2 CH2 CH2 CH2 CH2 CH3 H2C O HC O O O P O CH2 CH2 CH3 CH3 O– N+ CH3 Phospholipid • Hydrophylic • Variable phosphate groups found throughout membrane • e.g.: Phosphate Head • Standard CH2 O– • Hydrophobic • Variable numbers of carbons in chains • Variability in “C–C” bonds: Single, double, triple. H+ OP OH OH O P O • Phospholipid Bilayer: • basic structure of all cellular membranes (plasma and organelle) • Tails (fatty acid chains) face each other • Heads (Phosphate containing groups) face out. HO O– H+ OP