1. © 2012 Pearson Education, Inc. Lectures by Kathleen Fitzpatrick Simon Fraser University Chapter 2 The Chemistry of the Cell

2. © 2012 Pearson Education, Inc. The Chemistry of the Cell Five principles important to cell biology –Characteristics of carbon –Characteristics of water –Selectively permeable membranes –Synthesis by polymerization of small molecules –Self assembly

3. © 2012 Pearson Education, Inc. The Importance of Carbon Study of all classes of carbon-containing compounds is organic chemistry Biological chemistry (biochemistry) is the study of the chemistry of living systems The carbon atom (C) is the most important atom in biological molecules Specific bonding properties of carbon account for the characteristics of carbon-containing compounds

4. © 2012 Pearson Education, Inc. Bonding properties of the carbon atom The carbon atom has a valence of 4 (outermost electron shell lacks 4 of 8 electrons needed to fill it), so can form 4 chemical bonds with other atoms Carbon atoms are most likely to form covalent bonds with one another and with oxygen (O), hydrogen (H), nitrogen (N), and sulfur (S) Covalent bonds - the sharing of a pair of electrons between two atoms

5. © 2012 Pearson Education, Inc. Figure 2-1A

6. © 2012 Pearson Education, Inc. Covalent bonding of carbon atoms Sharing one pair of electrons between two atoms forms a single bond Double and triple bonds involve two atoms sharing two and three pairs of electrons, respectively Whether carbon atoms form single, double or triple bonds with other atoms, the total number of covalent bonds per carbon is four

7. © 2012 Pearson Education, Inc. Figure 2-1B-D

8. © 2012 Pearson Education, Inc. Carbon-Containing Molecules Are Stable Stability is expressed as bond energy - the amount of energy required to break 1 mole (~6x 10 23 ) of bonds Bond energy is expressed as calories per mole (cal/mol) A calorie is the amount of energy needed to raise the temperature of 1g of water by 1 o C A kcal (kilocalorie) is equal to 1000 calories

9. © 2012 Pearson Education, Inc. Bond energies of covalent bonds A lot of energy is needed to break covalent bonds –C-C, 83 kcal/mol –C-N, 70 kcal/mol –C-O, 84 kcal/mol –C-H, 99 kcal/mol Double and triple bonds are even harder to break –C=C, 146 kcal/mol –C≡C, 212 kcal/mol

10. © 2012 Pearson Education, Inc. Figure 2-2

11. © 2012 Pearson Education, Inc. Strong covalent bonds necessary for life Solar radiation has an inverse relationship between wavelength and energy content The visible portion of sunlight is lower in energy than C-C bonds So, visible light cannot break the bonds of organic molecules Higher energy, ultraviolet light, is more hazardous

12. © 2012 Pearson Education, Inc. Figure 2-3

13. © 2012 Pearson Education, Inc. Carbon-Containing Molecules Are Diverse A large variety of compounds can be formed by relatively few kinds of atoms Rings or chains of carbon atoms can form Chains may branch and may have single or double bonds between the carbons Variety of structures possible is due to the tetravalent nature of the carbon atom

14. © 2012 Pearson Education, Inc. Hydrocarbons Hydrocarbons are chains or rings composed only of carbon and hydrogen They are economically important, because petroleum products, including gasoline and natural gas, are hydrocarbons In biology, they are of limited importance because they are not soluble in water

15. © 2012 Pearson Education, Inc. Figure 2-4

16. © 2012 Pearson Education, Inc. Biological compounds These normally contain carbon, hydrogen, and one or more atoms of oxygen, as well as nitrogen, phosphorus, or sulfur These (O, N, P, S) are usually part of functional groups, common arrangements of atoms that confer specific chemical properties on a molecule

17. © 2012 Pearson Education, Inc. Functional groups Important functional groups include –Carboxyl and phosphate groups (negatively charged) –Amino groups (positively charged) –Hydroxyl, sulfhydroxyl, carbonyl, aldehyde (uncharged; but polar)

18. © 2012 Pearson Education, Inc. Figure 2-5A,B

19. © 2012 Pearson Education, Inc. Bond polarity In polar bonds electrons are not shared equally between two atoms Polar bonds result from a high electronegativity (affinity for electrons) of oxygen and sulfur compared to carbon and hydrogen Polar bonds have high water solubility compared to C-C or C-H bonds, in which electrons are shared equally

20. © 2012 Pearson Education, Inc. Figure 2-5C

21. © 2012 Pearson Education, Inc. Activity: Functional Groups Right click on animation / Click play

22. © 2012 Pearson Education, Inc. Carbon-Containing Molecules Can Form Stereoisomers The carbon atom is a tetrahedral structure When four atoms are bonded to the four corners of the tetrahedron, two spatial configurations are possible These non-superimposable configurations are mirror images, called stereoisomers

23. © 2012 Pearson Education, Inc. Figure 2-6

24. © 2012 Pearson Education, Inc. Activity: Isomers – Part 1 Right click on animation / Click play

25. © 2012 Pearson Education, Inc. Activity: Isomers – Part 2 Right click on animation / Click play

26. © 2012 Pearson Education, Inc. Activity: Isomers – Part 3 Right click on animation / Click play

27. © 2012 Pearson Education, Inc. Asymmetric carbon atoms An asymmetric carbon atom has four different substituents Two stereoisomers are possible for each asymmetric carbon atom A compound with n asymmetric carbons will have 2 n possible stereoisomers

28. © 2012 Pearson Education, Inc. Figure 2-7A

29. © 2012 Pearson Education, Inc. Figure 2-7B

30. © 2012 Pearson Education, Inc. The Importance of Water Water has an indispensable role as the universal solvent in biological systems It is the single most abundant component of cells and organisms About 75-85% of a cell by weight is water Its chemical characteristics make water indispensable for life

31. © 2012 Pearson Education, Inc. Water Molecules Are Polar Unequal distribution of electrons gives water its polarity The water molecule is bent rather than linear The oxygen atom at one end of the molecule is highly electronegative, drawing the electrons toward it This results in a partial negative charge at this end of the molecule, and a partial positive charge around the hydrogen atoms

32. © 2012 Pearson Education, Inc. Figure 2-8A

33. © 2012 Pearson Education, Inc. Water Molecules Are Cohesive Because of their polarity, water molecules are attracted to each other and orient so the electronegative oxygen of one molecule is associated with the electropositive hydrogens of nearby molecules Such associations, called hydrogen bonds, are about 1/10 as strong as covalent bonds

34. © 2012 Pearson Education, Inc. Hydrogen bonds and cohesiveness Water is characterized by an extensive network of hydrogen-bonded molecules, which make it cohesive The combined effect of many hydrogen bonds accounts for water’s high –Surface tension –Boiling point –Specific heat –Heat of vaporization

35. © 2012 Pearson Education, Inc. Surface tension of water Is the result of the collective strength of vast numbers of hydrogen bonds Allows insects to walk along the surface of water without breaking the surface Allows water to move upward through conducting tissues of some plants

36. © 2012 Pearson Education, Inc. Figure 2-9

37. © 2012 Pearson Education, Inc. Water Has a High Temperature- Stabilizing Capacity High specific heat gives water its temperature- stabilizing capacity Specific heat - the amount of heat a substance must absorb to raise its temperature 1 o C The specific heat of water is 1.0 calorie per gram, much higher than most liquids

38. © 2012 Pearson Education, Inc. Temperature-stabilizing capacity Heat that would raise the temperature of other liquids is first used to break numerous hydrogen bonds in water Water therefore changes temperature relatively slowly, protecting living systems from extreme temperature changes Without this characteristic of water, energy released in cell metabolism would cause overheating and death

39. © 2012 Pearson Education, Inc. Heat of vaporization Heat of vaporization is the amount of energy required to convert one gram of liquid into vapor This value is high for water because of the many hydrogen bonds that must be broken The high heat of vaporization of water makes it an excellent coolant

40. © 2012 Pearson Education, Inc. Water Is an Excellent Solvent A solvent is a fluid in which another substance, the solute, can dissolve Water is able to dissolve a large variety of substances, due to its polarity Most of the molecules in cells are also polar and so can form hydrogen bonds, or ionic bonds with water

41. © 2012 Pearson Education, Inc. Solutes Solutes that have an affinity for water and dissolve in it easily are called hydrophilic (generally polar molecules or ions) Many small molecules - sugars, organic acids, some amino acids - are hydrophilic Molecules not easily soluble in water - such as lipids and proteins in membranes are called hydrophobic (generally nonpolar molecules)

42. © 2012 Pearson Education, Inc. NaCl in water A salt, such as NaCl, exists as a lattice of Na + cations (positively charged) and Cl - anions (negatively charged) To dissolve in a liquid, the attraction of anions and cations in the salt must be overcome In water, anions and cations take part in electrostatic interactions with the water molecules, causing the ions to separate The polar water molecules form spheres of hydration around the ions, decreasing their chances of reassociation

43. © 2012 Pearson Education, Inc. Figure 2-10

44. © 2012 Pearson Education, Inc. Figure 2-10A

45. © 2012 Pearson Education, Inc. Figure 2-10B

46. © 2012 Pearson Education, Inc. Solubility of molecules with no net charge Some molecules have no net charge at neutral pH Some of these are still hydrophilic because they have some regions that are positively charged and some that are negatively charged Water molecules will cluster around such regions and prevent the solute molecules from interacting with each other Hydrophobic molecules, such as hydrocarbons tend to disrupt the hydrogen bonding of water and are therefore repelled by water molecules

47. © 2012 Pearson Education, Inc. The Importance of Selectively Permeable Membranes Cells need a physical barrier between their contents and the outside environment Such a barrier should be –impermeable to much of the cell contents –not completely impermeable, allowing some materials into and out of the cell –insoluble in water to maintain the integrity of the barrier –permeable to water to allow flow of water in and out of the cell

48. © 2012 Pearson Education, Inc. Membranes surround cells The cellular membrane is a hydrophobic permeability barrier Consists of phospholipids, glycolipids, and membrane proteins Membranes of most organisms also contain sterols - cholesterol (animals), ergosterols (fungi), or phytosterols (plants)

49. © 2012 Pearson Education, Inc. Membrane lipids are amphipathic Membrane lipids are amphipathic; they have both hydrophobic and hydrophilic regions Amphipathic phospholipids have a polar head, due to a negatively charged phosphate group linked to a positively charged group They also have two nonpolar hydrocarbon tails

50. © 2012 Pearson Education, Inc. Figure 2-11

51. © 2012 Pearson Education, Inc. Figure 2-11A

52. © 2012 Pearson Education, Inc. Figure 2-11B

53. © 2012 Pearson Education, Inc. Video: Dynamics of a Lipid Bilayer

54. © 2012 Pearson Education, Inc. A Membrane Is a Lipid Bilayer with Proteins Embedded in It In water, amphipathic molecules undergo hydrophobic interactions The polar heads of membrane phospholipids face outward toward the aqueous environment The hydrophobic tails are oriented inward The resulting structure is the lipid bilayer

55. © 2012 Pearson Education, Inc. Figure 2-12

56. © 2012 Pearson Education, Inc. Figure 2-13A

57. © 2012 Pearson Education, Inc. Figure 2-13B

58. © 2012 Pearson Education, Inc. Membrane proteins Membrane proteins may play a variety of roles –Transport proteins, for moving specific substances across an otherwise impermeable membrane –Enzymes, that catalyze reactions associated with the membrane –Receptors on the cell’s surface, and other proteins in mitochondrial or chloroplast membranes

59. © 2012 Pearson Education, Inc. Membranes Are Selectively Permeable Because of the hydrophobic interior, membranes are readily permeable to nonpolar molecules However, they are quite impermeable to most polar molecules and very impermeable to ions Cellular constituents are mostly polar or charged and are prevented from entering or leaving the cell However, very small molecules diffuse

60. © 2012 Pearson Education, Inc. Ions must be transported Even the smallest ions are unable to diffuse across a membrane This is due to both the charge on the ion and the surrounding hydration shell Ions must be transported across a membrane by specialized transport proteins

61. © 2012 Pearson Education, Inc. Transporter proteins Transport proteins act as either hydrophilic channels or carriers Transport proteins of either type are specific for a particular ion or molecule or class of closely related molecules or ions

62. © 2012 Pearson Education, Inc. The Importance of Synthesis by Polymerization Most cellular structures are made of ordered arrays of linear polymers called macromolecules Important macromolecules in the cell include proteins, nucleic acids, polysaccharides Lipids share some features of macromolecules, but are synthesized somewhat differently

63. © 2012 Pearson Education, Inc. Macromolecules Are Responsible for Most of the Form and Function in Living Systems Cellular hierarchy: biological molecules and structures are organized into a series of levels, each building on the preceding one Most cellular structures are composed of small water-soluble organic molecules, obtained from other cells or synthesized from nonbiological molecules (CO 2, NH 4, PO 4, etc.)

64. © 2012 Pearson Education, Inc. Hierarchical assembly The small organic molecules then polymerize to form biological macromolecules Biological macromolecules may function on their own, or assemble into a variety of supramolecular structures The supramolecular structures are components of organelles and other subcellular structures that make up the cell

65. © 2012 Pearson Education, Inc. Figure 2-14

66. © 2012 Pearson Education, Inc. Fundamental principle of biological chemistry The macromolecules that are responsible for most of the form and order of living systems are generated by the polymerization of small organic molecules The repeating units are called monomers; examples include the glucose present in sugar or starch, amino acids in proteins, and nucleotides in nucleic acids

67. © 2012 Pearson Education, Inc. Figure 2-15

68. © 2012 Pearson Education, Inc. Cells Contain Three Different Kinds of Macromolecules The major macromolecular polymers in the cell are proteins, nucleic acids, and polysaccharides Nucleic acids and proteins have a variety of monomers that may be arranged in nearly limitless ways; the order and type of monomer are critical for function Polysaccharides, composed of one or two monomers, have relatively few types

69. © 2012 Pearson Education, Inc. Table 2-1

70. © 2012 Pearson Education, Inc. Informational macromolecules Nucleic acids are called informational macromolecules because the order of the four kinds of nucleotide monomers in each is non- random and carries important information DNA and RNA serve a coding function, containing the information needed to specify the precise amino acid sequences of proteins

71. © 2012 Pearson Education, Inc. Proteins Proteins are composed of a nonrandom series of amino acids Amino acid sequence determines the three- dimensional structure, thus the function, of a protein With 20 different amino acids, a nearly infinite variety of protein sequences is possible Proteins have a wide range of functions including structure, defense, transport, catalysis, and signaling

72. © 2012 Pearson Education, Inc. Polysaccharides Polysaccharides typically consist of single repeating subunits or two altering subunits The order of monomers carries no information and is not essential for function Most polysaccharides are structural macromolecules (e.g., cellulose or chitin) or storage macromolecules (e.g., starch or glycogen)

73. © 2012 Pearson Education, Inc. Figure 2-16A

74. © 2012 Pearson Education, Inc. Figure 2-16B

75. © 2012 Pearson Education, Inc. Macromolecules Are Synthesized by Stepwise Polymerization of Monomers Despite some differences, the production of most polymers follows basic principles –1. Macromolecules are always synthesized by the stepwise polymerization of monomers –2. The addition of each monomer occurs by the removal of a water molecule (condensation reaction)

76. © 2012 Pearson Education, Inc. Basic principles (continued) –3. The monomers must be present as activated monomers before condensation can occur –4. To become activated, a monomer must be coupled to a carrier molecule –5. The energy to couple a monomer to a carrier molecule is provided by adenosine triphosphate (ATP) or a related high-energy compound –6. Macromolecules have directionality; the chemistry differs at each end of the polymer

77. © 2012 Pearson Education, Inc. Figure 2-17

78. © 2012 Pearson Education, Inc. Figure 2-17A

79. © 2012 Pearson Education, Inc. Figure 2-17B

80. © 2012 Pearson Education, Inc. Figure 2-17C

81. © 2012 Pearson Education, Inc. Carrier molecules A different kind of carrier molecule is used for each kind of polymer –For protein synthesis, amino acids are linked to carriers called transfer RNA (tRNA) –Sugars (often glucose) that form polysaccharides are activated by linking them to ADP (adenosine diphosphate), or UDP (uridine diphosphate) –For nucleic acids the nucleotides themselves are high- energy molecules (ATP, GTP)

82. © 2012 Pearson Education, Inc. Condensation and hydrolysis Activated monomers react with one another in a condensation reaction, then release the carrier molecule The continued elongation of the polymer is a sequential, stepwise process Degradation of polymers occurs via hydrolysis, breaking the bond between monomers through addition of one H + and one OH - (a water molecule)

83. © 2012 Pearson Education, Inc. The Importance of Self-Assembly After macromolecules are synthesized, further steps are needed for assembly into higher-order structures The principle of self-assembly states that information needed to specify the folding of macromolecules and their interactions to form complex structures is inherent in the polymers themselves

84. © 2012 Pearson Education, Inc. Many proteins self-assemble The immediate product of amino acid polymerization is a polypeptide Once the polypeptide has assumed its correct three dimensional structure, or conformation, it is called a protein The native (natural) conformation of a protein can be altered by changing conditions such as the pH or temperature or treating with certain chemical agents

85. © 2012 Pearson Education, Inc. Denaturation and renaturation The unfolding of polypeptides, denaturation, leads to loss of biological activity (function) When denatured proteins are returned to conditions in which the native conformation is stable, they may undergo renaturation, a refolding into the correct conformation In some cases, renaturation is associated with the return of the protein function (e.g., ribonuclease)

86. © 2012 Pearson Education, Inc. Figure 2-18A

87. © 2012 Pearson Education, Inc. Figure 2-18B

88. © 2012 Pearson Education, Inc. Molecular Chaperones Assist the Assembly of Some Proteins Some proteins require molecular chaperones, which assist the assembly process by inhibiting interactions that would produce incorrect structures Under lab conditions, such proteins do not regain their native conformation after the conditions of denaturation are reversed Molecular chaperones are not components of the completed structures and they convey no information

89. © 2012 Pearson Education, Inc. Types of self-assembly and chaperones Strict self-assembly - no factors other than the polypeptide sequence itself are needed Assisted self-assembly - requires a specific molecular chaperone to ensure that the correct conformation predominates over incorrect forms Chaperone proteins are abundant, and even moreso under stresses such as high temperature Many chaperones fall into one of two categories of heat shock proteins

90. © 2012 Pearson Education, Inc. Noncovalent Bonds and Interactions Are Important in the Folding of Macromolecules Covalent bonds link the monomers of a polypeptide together and can stabilize the three-dimensional structure of many proteins However, four other types of interactions are important for the folding of proteins –Hydrogen bonds (previously discussed) –Ionic bonds –Van der Waals interactions –Hydrophobic interactions

91. © 2012 Pearson Education, Inc. Ionic bonds Ionic bonds are noncovalent electrostatic interactions between two oppositely charged ions They form between negatively charged and positively charged functional groups Ionic bonds between functional groups on the same protein play an important role in the structure of the protein Ionic bonds may also influence the binding between macromolecules

92. © 2012 Pearson Education, Inc. Van der Waals interactions Van der Waals interactions (or forces) are weak attractions between two atoms that only occur if the atoms are very close to one another and oriented appropriately Atoms that are too close together will repel one another The van der Waals radius of an atom defines how close other atoms can come to it, and is the basis for space-filling models of molecules

93. © 2012 Pearson Education, Inc. Figure 2-19

94. © 2012 Pearson Education, Inc. Hydrophobic interactions Hydrophobic interactions describes the tendency of nonpolar groups within a macromolecule to associate with each other and minimize their contact with water These interactions commonly cause nonpolar groups to be found in the interior of a protein or embedded in the nonpolar interior of a membrane

95. © 2012 Pearson Education, Inc. Self-Assembly Also Occurs in Other Cellular Structures The same principles of self-assembly that apply to polypeptides also apply to the assembly of more complex structures Many such structures are composed of complexes of two or more kinds of polymers Ribosomes, membranes, primary cell wall (plants)

96. © 2012 Pearson Education, Inc. The Tobacco Mosaic Virus Is a Case Study in Self-Assembly A virus is a complex of nucleic acids and proteins that uses living cells to produce more copies of itself via self-assembly A good example is the tobacco mosaic virus (TMV) It is a rodlike particle, with a single RNA strand and about 2130 copies of a coat protein that form a cylindrical covering for the RNA

97. © 2012 Pearson Education, Inc. Figure 2-20

98. © 2012 Pearson Education, Inc. Self-assembly of TMV is quite complex The unit of assembly is a two-layered disc of coat protein that changes conformation (from cylinder to helix) as it interacts with the central RNA molecule This conformational change allows another disc to bind and to interact with the RNA, and thus change its conformation as well The process repeats until the end of the RNA molecule is reached

99. © 2012 Pearson Education, Inc. Figure 2-21A,B

100. © 2012 Pearson Education, Inc. Figure 2-21C,D

101. © 2012 Pearson Education, Inc. Video: Tobacco mosaic virus (TMV)

102. © 2012 Pearson Education, Inc. Self-Assembly Has Limits Some assembly systems depend additionally on information provided by a preexisting structure Examples –Membranes –Cell walls –Chromosomes

103. © 2012 Pearson Education, Inc. Hierarchical Assembly Provides Advantages for the Cell Hierarchical assembly is the dependence on subassemblies that act as intermediates of the process of assembly of increasingly complex structures Biological structures are almost always assembled hierarchically

104. © 2012 Pearson Education, Inc. Advantages of hierarchical assembly Chemical simplicity - relatively few subunits are used for a wide variety of structures Efficiency of assembly - a small number of kinds of condensation reactions are needed Quality control - defective components can be discarded prior to incorporation into higher-level structure, reducing the waste of energy and materials