Biochemistry

1. Biochemistry Introduction

3. Biochemistry as a Discipline Biochemistry as a Chemical Science Amino acidsSugarsLipidsNucleotidesVitaminsHormones

4. Chemical Elements of Living Matter

5. Monomers/Polymers Sugar/PolysaccharideNucleotide/Nucleic AcidsAmino acid/Polypeptides

6. Biochemistry as a Biological Science Distinguishing Characteristics of Living Matter Constant renewal of a highly ordered structure accompanied by an increase in complexity of that structure Overcoming entropy requires energy Life is self-replicating

7. Range of sizes of objects studied by biochemists and biologists

8. Uses of Biochemistry Agriculture: Herbicides and pesticides Medicine : Monocloning antibodies Nutrition : Vitamines Clinical Chemistry: transaminases and bilirubin/Liver disease Pharmacology: penicillin (inhibiting an enzyme that synthesizes an essential polysaccharide of the bacterial cell wall) Toxicology:

9. designer drugs If the target site for action of a drug is a protein enzyme or receptor, determining the detailed molecular structure of that target allows us to design inhibitors that bind to it with great selectivity.

10. Biochemistry Background

11. 1.Covalent and Noncovalent bond Covalent Bonds (300-400 kJ/mol) Non-Covalent Interactions (2-40 kJ/mol) Hydrogen BondsCharge-charge interactionsOther non-covalent interactions

12. Charge-Charge Interactions Coulomb's law F = k*(q1q2)/r2 dielectric medium, F = k*(q1q2)/ ? r2

13. Hydrogen Bonds hydrogen bond donor :to which hydrogen is covalently bonded hydrogen bond acceptor : with the nonbonded electron pair

14. 2. The Role of Water in Biological Processes Hydrophilic molecules in Aqueous Solution (Figure 2.11) Hydrophobic molecules in Aqueous Solution Clathrate cages (Figure 2.13) Amphipathic molecules in Aqueous

15. Water 

16. Hydrophilic molecules

17. Hydrophobic molecules Clathrate cages

18. Amphipathic molecules

19. 3. pH Acids and Bases: Proton Donors and Acceptors pH = -log[H+] Weak Acid and Base Equilibria Ka and pKa  Ka=[H+][A-]/[HA] ? pKa=pH-log [A-]/[HA] Polyprotic Acids

20. The pH Scale and the Physiologic pH Range

21. Henderson-Hasselbalch Equation, pI Titration of Weak Acids: The Henderson-Hasselbalch Equation: pH = pKa +log [A-]/[HA] pI : Each molecule has a distinct pH (called the pI or isoelectric point) at which the net average charge of all the groups adds up to zero. If acidic groups predominate, the pI will be low. If basic groups predominate, the pI will be high.

22. Acid dissociation of glycine Glycine has only a single acidic group and a single basic group, the pI can be determined by averaging the pKas of the two groups (from Equation 2.18) For example, the pKa values of the carboxylate and amino groups on glycine are 2.3 and 9.6, respectively. Thus, pI = (2.3 + 9.6)/2 = 5.95

23. The relative concentrations of the three forms of glycine as a function of pH.

24. 4. Interactions Between Macroions in Solution Solubility of Macroions and pH (Figure 2.20, Figure 2.21) Repulsive effects (nucleic acids) Attractive effects (histones to DNA) Minimum solubility at isoelectric point Influence of Small Ions: Ionic Strength (Figure 2.22)

25. Figure 2.20 Electrostatic interactions between macroions

26. Figure 2.21

28. Debye-Huckel Theory Salting In - adding counterions to a point increases protein solubility Salting Out - adding very large amounts of counterions decreases protein solubility

29. 5. Entropy and the Second Law of Thermodynamics Entropy (S) Tendency of Systems of Molecules to RandomizationS = klnW (k = Boltzmann constant)

30. Second Law "The entropy of an isolated system will tend to increase to a maximum value"

31. 6. Free Energy: The Second Law in Open Systems G = H - TS G = H - T S G <0 means Exergonic, favorable process G >0 means Endergonic, reverse process favored

32. Free Energy and Chemical Reactons: Chemical Equilibrium Free Energy Change and the Equibrium Constant = Standard State Free Energy Change = + RTln([products]/[reactants]) = + RTlnK, where K is equilbrium constant

33. Free Energy Calculations A Biochemical Example : 1. G6P <=> F6P ( = +1.7 kJ/mol means equilibrium concentration has more G6P than F6P)2. Plugging this into , one finds that (F6P)/(G6P) = 0.5043. Since G = + RTln([products]/[reactants]), displacements away from equilibrium will be moved towards equilibrium by corresponding force of free energy change brought about by the change. (Figure 3.6)

35. How Cells Use Energy Light from the sun is the ultimate source of energy for all life on earth photosynthetic organisms use light energy to drive the energy-requiring synthesis of carbohydrates non-photosynthetic organisms consume these carbohydrates and use them as energy sources

36. 7.Common Ground for Cells Eukaryotes are complex; how did such cells arise from simplest progenitors? Mutualism: a symbiotic association between two organisms that gives rise to a new organism combining characteristics of both original types the lichen, which consists of a fungus and an alga the root nodule system formed by a leguminous plant and anaerobic nitrogen-fixing bacteria humans and bacteria such as Escherichia coli that live in the human intestinal tract

37. Common Ground for Cells a similar model can be proposed for the origin of chloroplasts the fact that mitochondria and chloroplasts have their own DNA and their own apparatus for the synthesis of RNA and proteins supports this model These proposed connections between prokaryotes and eukaryotes are not established with complete certainty Still they provide an interesting framework from which to consider the reactions that take place in cells

38. The root nodule root nodule system formed by a leguminous plant and anaerobic nitrogen-fixing bacteria

39. Escherichia coli