1. Foundations of Biochemistry Doba Jackson, Ph.D. Dept. of Chemistry & Biochemistry Huntingdon College

2. What distinguishes living organisms from other forms of matter? High degree of chemical complexity and organization (muscle tissue) System for extracting energy from the environment (bird) The ability to self-replicate (zebra) Ability to sense changes in the surroundings and respond Defined functions of each component and regulated interactions The ability to adapt with time (evolution)

3. Chemical Foundations “What are the common chemical principals important to all cells”

4. Only 30 of the 90 naturally occuring elements are found in biological systems

5. Components of macromolecules: the ABC’s of Biochemistry Proteins Nucleic AcidsLipids Carbohydrates

6. You must remember all of these functional groups!!!!! Biomolecules are hydrocarbons with attached functional groups

7. What do these have in common? Hydrocarbons

8. What do these have in common? All have carbon-oxygen bonds

9. What do these have in common? All have carbon-nitrogen bonds

10. What do these have in common? All have carbon-sulfur bonds

11. What do these have in common? All have carbon-phosphate bonds

12. Some Definitions Chiral center- a carbon atom with four different a substituents (ie.- asymmetric carbon) Enantiomers- pairs of stereoisomers that are mirror images of each other. Diastereomers- pairs of stereoisomers that are not mirror images of each other.

13. 4 substituents 3 substituents EnantiomersSame molecule

14. Example: 2,3 disubstituted butanes

15. Stereoisomers distinguisable by taste Aspartate Phenylalanine

16. Summary of chemical foundations Only 30 of the 90 naturally occuring elements are found in biological systems 99.9% of biomolecules are considered organic compounds Most biomolecules have more than one functional group Conformation, configuration, and constitution are all important factors for determination of biological activity

17. Aqueous Solutions By Doba D. Jackson, Ph.D. Dept. of Chemistry & Biochemistry Huntingdon College

18. Why study Water Water is the most abundant chemical in living systems making up to 70% of the mass of most organisms. The attractive forces between water molecules and the slight tendency of water molecules to ionize are of crucial importance to the structure and function of biomolecules.

19. Outline of Discussion Weak interactions in aqueous solution –Hydrogen Bond –Nonpolar compounds and water insolubility –Hydrophobic interactions, van Der waals interactions Ionization of water, weak acids and bases –Review acids, bases, K w and pKa Buffers, pH changes in biological systems –Phosphate, Carbonate buffers in living organisms –Tris, HEPES buffers commonly used in laboratories

21. Structure of a water molecule Less than 109.5º - The Oxygen bears two partial negative charges each aligned with the p-orbitals. - Each Hydrogen bears a positive charge aligned 104.5º from the OH bond.

22. The Hydrogen Bond “ I believe that as the methods of Structural chemistry (x-ray crystallography) are further applied to physiological problems, it will be found that the significance of the hydrogen bond for physiology is greater than that of any other single structural feature” -Linus Pauling, The Nature of the Chemical Bond (1939)

23. The Hydrogen Bond - The hydrogen atom becomes between covalently bound oxygen and the oxygen aligned from its neighbor. - The hydrogen bond has a dissociation energy of 23 kJ/mol (compared to 470 kJ/mol). - Based on orbital overlap, the hydrogen bond is 10% covalent and 90% electrostatic. - The total hydrogen bond length is approximately 2.8 Ǻ ( ~ 3 Ǻ ).

24. Hydrogen bonding in ice -Solid ice 2 covalent bonds 4 hydrogen bonds 6 total bonds -Liquid water 2 covalent bonds 2.4 hydrogen bonds 4.4 total bonds

25. Hydrogen Bonds other than water Any electronegative atom (usually N, O) with a pair of electrons can attract a hydrogen attached to another electronegative atom.

26. Examples of Biologically important hydrogen bonds Alcohol & water Ketone & water Between amino acids in proteins DNA strands

27. Water as a solvent - Polar solutes : compounds that have polar bonds; usually dissolve easily in water. - Nonpolar solutes: compounds that do not have polar bonds; usually difficult to dissolve in water but dissolves easily in nonpolar solvents (hexane, chloroform or benzene). - Amphipathic solutes: compounds with polar and nonpolar groups; solubility will vary.

30. –Water at a hydrophobic surface loses a hydrogen bond. –Water molecules compensate for this by creating a low-density water network with lower entropy directly surrounding the hydrophobic solute. –Water covers the surface with clathrate-like hexagons, so avoiding the loss of most of the hydrogen bonds. What happens to the structure of water at a hydrophobic interface?

32. Hydrophobic Effect

33. Release of ordered water can drive the formation of an enzyme-substrate complex

34. Review weak (noncovalent) molecular interactions Electrostatic (ionic) interactions- The attractive forces between oppositely charges molecules or functional groups. Hydrogen Bonds- an interaction between a hydrogen covalently attached to an electronegative atom and the electron pair of another electronegative atom. Hydrophobic interactions- the strong tendency of water to minimize the surface area surrounding nonpolar groups or molecules. Van der Waals forces- are the result of induced electrical interactions of closely approaching atoms as their negative electron clouds fluctuate with time.

35. Van der Waals forces

36. .4 – 4.0.3 -.6 Hydrogen bonds12 – 30.3 Ionic interactions20.25 Hydrophobic interactions <40>1 Strength (kJ/mol) Distance (nm) Weak chemical forces and their strengths and distances Hydrophobic interactions can act across very large distances which makes these interactions very dominant in determining macromolecular structure and function strength

37. “Proton hopping” common in enzymes that translocate protons across cell membranes Cytochrome f; in photosynthesis

38. Weak interactions are crucial to macromolecular structure and function For macromolecules (DNA, RNA & proteins) the most stable structure is one that maximizes the weak bonding possibilities.

40. Titration curves can reveal dissociation constants (pKa) and buffer ranges

41. Henderson-Hasselbalch Equation: relationship between pH, pKa and buffer concentrations CH 3 COOH CH 3 COO - + H +

43. Typically a buffer is best when it is within.5 units of its pKa

44. Blood, Lungs and extracellular fluid is buffered by carbonate Vigorous Exercise (lactic acid) Blood, extracellular Fluid Lungs, Air space Vigorous Exercise Typical catabolism raises pH Typical catabolism raises pH

45. Enzymes have specific pH optimums due to the combination of many functional groups