Biomolecular Principles: Nucleic Acids & Proteins

1. BIO307- Bioengineering principles SPRING 2019 Lecture 2 Biomolecular Principles: Nucleic Acids and Proteins Lecturer: Jasmin Sutkovic 4.3.2019

2. Content • Introduction • Bonding between atoms and molecules • Water: The medium of Life • Biochemical Energetics • Macromolecules: Polymers of Biological importance • Lipids

3. Why should biomedical engineers understand chemistry ? • Knowing how molecules interact with each other and with their environments helps biomedical to manipulate these molecules to create new tools for treating disease. • Biomedical engineers helped to develop methods to synthesize lipid molecules into liposomes. • They helped to understand the formation of complexes, such as the extracellular clumps of protein-rich materials (plaques) that form in Alzheimer’s disease • Magnetic resonance imaging (MRI), is derived from a method that has been used for decades by chemists to understand molecules and their interactions.

4. Bonding between atoms and molecules All basic life processes that allow us to digest food, move, and grow involve chemical reactions: reactions that yield energy, build new molecules, or break down unneeded molecules. The molecules in our body are involved in thousands of chemical reactions. Before learning about the function of biological molecules, it is useful to examine the ways they can interact with one another by reviewing key concepts in chemistry.

5. Atomic bonding • Covalent and Ionic bonding • Covalent: Sharing of electrons between nonmetals • Ionic: metals deliver to nonmetals the electrons

6. Atomic bonding • Ions are molecules with a net charge, either positive or negative. • Ionic bonds are formed when electrons are transferred from one atom to another (e.g., Na+Cl−). • This transfer results in two ions: a positively charged molecule, or cation, caused by the loss of electrons, and a negatively charged molecule, or anion, caused by the gain of electrons

7. Covalent bonding • Covalently bonded molecules can further be classified as polar or nonpolar. Molecules are called “polar” because they have partially negative and partially positive charges at the poles of the molecule. • This polarity of charge is caused by unequal sharing of electrons between atoms within a molecule. • For example, water (H2O) is a polar molecule because the oxygen atom within the molecule is slightly negative, whereas the hydrogen atoms are slightly positive

9. Gene delivery • Biomedical engineers are frequently involved in synthesis of new molecules for medical applications. • One example is dendritic polymer (Dendrimer) for gene delivery to the cell. • These new agents are created by the formation of new covalent bonds between simple precursor molecules.

10. Dendrimer • Seek out and destroy cancer cells • Targeted drug delivery • Improved imaging • Cancer cell death confirmations • More on : https://www.youtube.com/watch?v=RBjWwlnq3cA&index=4&list=PLB059583D3676221C

11. Molecular bonding • Two molecules can be weakly attracted to one another through intermolecular forces. • These forces may include van der Waals interactions and hydrogen bonding.

13. Van der Waals interactions are also weak non-covalent attractions but they are due to temporary and unequal electron distributions around atoms . • Attractive and Repulsive forced between atoms, molecules, surfaces and other intermolecular forces. • So molecules can attract each other at moderate distances and repel each other at close range. The attractive forces are collectively called van der Waals forces http://ami.org/meetings/2016/2016/07/17/van-der-waals-forces-in-the-gecko-foot/

14. Water: The medium of life • Source of life- all chemical reactions occur in the presence of water/aquous rich environment • Water can be a product or a reactant in other chemical reactions • The extensive hydrogen bonding network that can form between water molecules gives rise to its unique properties. • These properties include high melting and boiling temperatures, high surface tension, and a higher density than ice

16. Properties of water • Excellent solvent • Water can easily dissolve ions or other polar molecules that are capable of forming hydrogen bonds • These water-soluble molecules are referred to as hydrophilic (“water loving”). • Nonpolar molecules are not easily dissolved in water and are called hydrophobic (“water fearing”). • Hydrophobic molecules aggregate together to exclude water as best they can: This behavior is often described as the hydrophobic effect.

17. Protein folding The hydrophobic effect is an important driving force in protein folding, the process by which a long macromolecule of amino acids forms a three-dimensional, biologically active proteinmolecule (Figure 2.8).

18. Amphiphilic molecules • Molecules that contain both hydrophilic and hydrophobic groups are called amphiphilic. • For example, phospholipids are amphiphilicmolecules that form the plasma membrane surrounding cells. • Bioengineers use these kinds of molecules to form complex structures such as the liposomes described earlier.

19. Biochemical energetics • Food=energy • We store energy in the form of triglycerides and glycogen and we use it when needed! • We need and/or release energy – depending on several factors. • Water is formed by the reaction of hydrogen atoms and oxygen atoms

20. The total energy change for a reaction, depends on the net energy change for all of the bonds broken and formed. • The overall heat of formation—or enthalpy change of formation reaction—is a measure of the amount of energy that is either consumed or released when water is formed and is called H(f) . • Energy is measured at standard conditions, 25◦C and 1 atm. Appendix B contains a table with heats of formation for some compounds! The Hfis equal to −242 kJ/mole for gaseous water and −286 kJ/mole for liquid water.

21. Delta H (overall energy change) • Heats of formation can be used to calculate the enthalpy change for other kinds of reactions. Consider the more general chemical reaction: aA+ bB → cC + dD • DH = SHproducts - SHreactants

22. A negative Hfindicates an exothermic reaction, in which heat is released as the reaction proceeds. • A positive Hfmeans that the reaction absorbs heat, or is endothermic. • The entropy (S) of a system is a measure of disorder in a system or the amount of energy in a system that cannot be used to do work. • The standard entropy change, deltaS, can be calculated similarly to H◦ by using standard entropy tables. • The energetics of biochemical reactions are often described in terms of Gibbs free energy, G, which is related to both the enthalpy and entropy:

23. ΔG determines the direction and extent of chemical change

24. ΔG determines the direction and extent of chemical change

25. Kinetics of chemical reactions • Study of rates of reactions or rates of change in chemical systems is called chemical kinetics • Reaction Rate: The change in the concentration of a reactant or a product with time (M/s).

26. The rate of a reaction is the speed at which a chemical reaction happens. If a reaction has a low rate, that means the molecules combine at a slower speed than a reaction with a high rate. • Some reactions take hundreds, maybe even thousands, of years while others can happen in less than one second. • If you want to think of a very slow reaction, think about how long it takes plants and ancient fish to become fossils (carbonization). • The rate of reaction also depends on the type of molecules that are combining. If there are low concentrations of an essential element or compound, the reaction will be slower. 

27. To illustrate chemical kinetics, consider the important biochemical reaction between water and carbon dioxide: The net amount of change in the concentration of any of the chemical species would depend on the rate of the forward reaction (which is consuming water and carbon dioxide and generating carbonic acid) and the rate of the reverse reaction (which is doing the opposite).

28. Chemcial equilibrium • When f and r reactions reach an equilibrium (kf=kr) or • K (equilibrium konstarnt)= kf/kr • K is related to the standard free-energy change, ΔG

29. ATP formation • One of the most important chemical reactions for energy utilization in cells involves another molecule, ATP • Similar to nucleotides, ATP has three phosphate groups linked together (whereas the nucleotide adenosine of DNA has only one phosphate).

30. Hydrolysis of P releases energy ATP+ Water results in ADP Releases 30.5 kJ/mole of energy;

31. Hydrolysis of ATP

32. Importance of pH Water dissociates—or breaks down into components—in solution. H+—hydrogen without an electron—is a proton and OH- is a hydroxide ion

33. Hydronium ion. However, free hydrogen ions do not exist in solution; because they are so small and positively charged, protons associate with water (the positively charged proton is attracted to the negative pole of water at the oxygen atom

34. Dissociation of Water • In fact, the concentrations of the dissociated H+ and OH− in pure water at 25C are, respectively, 10−7 M and 10−7 M. • One way to describe the extent of dissociation is to report the number of ions in solution: 10−7 M each of H+ and OH− in this case. • Small number represents a problem… 0.0000001 mol/l= 10−7 M

35. pH (for potential of hydrogen) • Defined as a negative logarithm of the hydrogen ion concentration: Thus, for pure water, with 10−7 M of protons, the pH is equal to 7. A solution in this state is called neutral, meaning that the solution has an equal number of H+ and OH− ions.

36. pH change in disease • Human blood pH normally is tightly regulated between 7.35 and 7.45. • The lower the pH, the more acidic the blood

37. For example, most enzymes function in or near the neutral physiological pH of 7.4, • Some enzymes function in acidic environments, such as the digestive enzymes in the stomach

38. pH scale

39. Acid and Bases • Home assignment 1 • On one page (A4) define Strong acids/Strong bases, and give few examples

40. Macromolecules: Polymers of biological importance • Polysaccharides • Proteins • Nucleic acids • Lipids

41. Nucleic acids, proteins, and polysaccharides are members of a more general class of chemicals called polymers, which are large molecules formed by the bonding of many smaller chemicals, called monomers, into one long molecule

42. The chemical process of making a polymer from a collection of monomers is called polymerization.

43. Polyethylene is manufactured and used in a wide range of products including plastic bags, tubing, packaging materials, furniture, toys, and medical implants

44. MONOMER DIVERSITY • Polysaccharides are made up of small sugars called monosaccharides, proteins are formed using amino acids, and nucleic acids are composed of nucleotides. • These polymeric biomolecules contain hundreds (carbohydrates and proteins) to millions (nucleic acids) of monomers

45. Classes of biological polymers

46. Lipids • Lipids are not polymers, but they are large molecules built from smaller units to create a diversity of structures. • Lipids include triglycerides, which are used for energy storage, and phospholipids, which assemble into cell membranes. • The properties of lipids are introduced in the next section, after the discussion of biological polymers.

47. FUNCTIONAL GROUPS IN MONOMERS

48. Example: Acetyl coenyme A Acetyl coenzyme A or acetyl-CoA is an important molecule in metabolism, used in many biochemical reactions. Its main function is to convey the carbon atoms within the acetyl group to the citric acid cycle (Krebs cycle) to be oxidized for energy production.

49. Carbohydrates • Monosaccharides, Disaccharides, and Polysaccharides. • A disaccharide is created by coupling together two monosaccharides, and a polysaccharide is formed by linking together many monosaccharides.

50. Monosaccharides • Monosaccharides typically form cyclic structures in aqueous solutions; the bonding of atoms within the molecule creates a ring. • Among the most common monosaccharides are the five-carbon sugars ribose and deoxyriboseand the • six-carbon sugars glucose, fructose, and galactose