1. The Chemistry of the Cell
Chapter 2
The Chemistry of the Cell

2. 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. 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. 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. Figure 2-1A
Atoms and valences

6. 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. Figure 2-1B-D

8. Carbon-Containing Molecules Are Stable
Stability is expressed as bond energy - the amount of energy required to break 1 mole (~6x 1023) 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 1oC
A kcal (kilocalorie) is equal to 1000 calories

9. 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. Figure 2-2

11. 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. Figure 2-3

13. 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. 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. Figure 2-4

16. 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. Functional groups Important functional groups include
Carboxyl and phosphate groups (negatively charged)
Amino groups (positively charged)
Hydroxyl, sulfhydroxyl, carbonyl, aldehyde (uncharged; but polar)

18. Figure 2-5A,B

19. 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. Figure 2-5C

21. Activity: Functional Groups

22. 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. Figure 2-6

24. Activity: Isomers – Part 1

25. 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 2n possible stereoisomers

26. Figure 2-7A

27. Figure 2-7B
May not need to separate a and b

28. 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

29. 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

30. Figure 2-8A

31. 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

32. 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

33. 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

34. Figure 2-9

35. 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 1oC
The specific heat of water is 1.0 calorie per gram, much higher than most liquids

36. 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

37. 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

38. 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

39. 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)

40. 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

41. Figure 2-10

42. Figure 2-10A

43. Figure 2-10B

44. 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

45. 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

46. 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)

47. 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

48. Figure 2-11

49. Figure 2-11A

50. Figure 2-11B

51. Video: Dynamics of a Lipid Bilayer

52. 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

53. Figure 2-12

54. Figure 2-13A

55. Figure 2-13B

56. 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

57. 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

58. 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

59. 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

60. 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

61. 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 (CO2, NH4, PO4, etc.)

62. 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

63. Figure 2-14

64. 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

65. Figure 2-15

66. 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

67. Table 2-1

68. 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

69. 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

70. 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)

71. Figure 2-16A

72. Figure 2-16B

73. 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)

74. 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

75. Figure 2-17

76. Figure 2-17A

77. Figure 2-17B

78. Figure 2-17C

79. 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)

80. 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)

81. 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

82. 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

83. 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)

84. Figure 2-18A

85. Figure 2-18B

86. 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

87. 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

88. 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

89. 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

90. 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

91. Figure 2-19

92. 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

93. 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)

94. 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

95. Figure 2-20

96. 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

97. Figure 2-21A,B

98. Figure 2-21C,D

99. Self-Assembly Has Limits
Some assembly systems depend additionally on information provided by a preexisting structure
Examples
Membranes
Cell walls
Chromosomes

100. 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

101. 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