1. Molecules, Gene and disease Session 1 Dr. Mona Abdel Ridha Rasheed Introduction to the cell and biological molecules

2. Learning Outcomes At the end of this session you should be able to: 1. Identify the main organelles in a mammalian cell and list their functions. 2.List the principal differences between a prokaryotic and an eukaryotic cell. 3. Discuss the bonds important for macromolecular structure and interaction. 4.Explain the differences between hydrophobic and hydrophilic molecules in water.

3. Learning Outcomes 5. Explain the concept of pH, pK and buffers. 6. Recognise and draw the generalised structure of an amino acid. 7. Classify amino acids according to the properties of their side chains. 8. Explain how the charges on amino acids are affected by pH. 9. Show how a peptide bond is formed and list its key features. 10. Explain how amino acid charge can influence the isoelectric point of a protein.

4. Structure of the session 1 Lecture 1: Introduction to the cell (8.00-8.50)  Lecture 2: Amino acids and protein (8.50-9.40)

5. Lecture 1 Introduction to the cell

6. The Cell-Basic Unit of Life  Cells are the structural and functional units of all living organisms.  Cells are capable of carrying out all the activities necessary for life.  Cells are small, membrane enclosed units filled with a concentrated aqueous solution of chemicals and provide with the surprising ability to create copies of themselves by growing and dividing in two.

7. Cell Components 1- Plasma membrane: It is a phospholipid bilayer that responsible for the cell morphology and movement, and transport of ions and small molecules. 2- Cytosol: liquid portion of cytoplasm (cytoplasm composed of all materials contained within cytosol). 3- Organelles: complex intracellular locations where processes necessary for eukaryotic cellular life occur. Most organelles are membrane enclosed structures, each organelle carries out a specific function.

8. Mammalian cell: Organelles

9. Mammalian Cell: Organelles functions FunctionsOrganelles RNA synthesis RNA processing and ribosome assembly( nucleolus) DNA synthesis and repair Nucleus/nucleolus Protein synthesisRibosome Export of proteins, Membrane synthesis, Lipid and steroid synthesis, Detoxification reactions (Protein synthesis) Endoplasmic reticulum Export of proteins, Detoxification reactionsGolgi complex ATP synthesisMitochondrion Cellular digestionLysosome Fatty acids and purine brake down, Detoxification of hydrogen peroxide, and synthesis of cholesterol, bile acids and myelin peroxisomes

10. Cell ProkaryoticEukaryotic Pro = before Lack a nucleus but have nucleoid which has a large DNA molecule. Lack intracellular organelles. Have a cell wall Ex: bacterial cell Eu =well or truly Karyon = nucleus Organisms whose cells have a nucleus are called eukaryotic Ex: mammalian cells

11. Cell component

12. Macromolecules

13. Subunits of Macromolecules

14. Bonds important for macromolecular structure and interaction Covalent bond: A covalent bond forms when two atoms come very close together and share one or more of their electrons. Each atom forms a fixed number of covalent bonds.

15. Bonds important for macromolecular structure and interaction

16. Ionic bond: A bond formed between two atoms where there is a complete transfer of an electron resulting in the formation of two ions (one positive and one negative ). e.g. NaCl It should be differentiate between ionic bond and ionic interaction which may be attraction ( between two groups with different charges), or Repulsion (between two groups with the same charges)

17. Bonds important for macromolecular structure and interaction Hydrogen bond: A weak electrostatic interaction between a hydrogen atom bound to an electronegative atom (N, O) and another electronegative atom.

18. Bonds important for macromolecular structure and interaction Hydrophobic interaction: A weak electrostatic interaction between two hydrophobic groups. Van der Waals interaction: A weak interaction between any two atoms in close proximity

19. Bonding

20. Bond length and strength

21. Water The principal fluid medium of the cell is water, which is present in most cells, except for fat cells, in a concentration of 70 to 85 per cent. Many cellular chemicals are dissolved in the water.

22. Water  WATER is the solvent of choice for biological systems  Helps regulate temperature since it is able to absorb large amounts of heat  Helps regulate intracellular pH  Used for transport – delivers nutrients and removes waste from cells  In water, the hydrogen atoms have a partial positive charge, and the oxygen atoms have a partial negative charge, so water is polar solvent

24. Water as a solvent

25.  Water is a polar molecule. It can readily dissolve biomolecules that are charged or polar. Molecules that can interact with water via hydrogen bonds are said to be hydrophilic.  Non-polar molecules are insoluble in water and interact with other non-polar compounds; they are said to be hydrophobic.  Molecules that have both hydrophilic and hydrophobic properties are said to be amphipathic.

28.  Some examples of polar, non-polar and amphipathic biological molecules are shown below:

29. pH and buffer  Ionization of Water Water dissociates into hydronium (H3O+) and hydroxyl (OH-) ions. For simplicity, we refer to the hydronium ion as a hydrogen ion (H+) and write the equilibrium as:

30.  K w is the ion product of water. At 25°C, K w is 1.0 × 10-14.  Note that the concentrations of H+ and OH- are reciprocally related.  If the concentration of H+ is high, then the concentration of OH- must be low, and vice versa.  For example, if [H+] = 10 -2 M, then [OH-] = 10 -12 M.

31. Definition of Acid and Base  An acid is a proton donor.  A base is a proton acceptor.  The species formed by the ionization of an acid is its conjugate base. Conversely, protonation of a base yields its conjugate acid. Acetic acid and acetate ion are a conjugate acid-base pair.

32. Definition of pH and pK The pH of a solution is a measure of its concentration of H+. The pH is defined as: The ionization equilibrium of a weak acid is given by: The apparent equilibrium constant K a for this ionization is: The pK a of an acid is defined as: The pK a of an acid is the pH at which it is half dissociated, when [A-]=[HA].

33. Henderson-Hasselbalch Equation  What is the relation between pH and the ratio of acid to base? Therefore And This equation is commonly known as the Henderson- Hasselbalch equation.

34.  The pH of a solution can be calculated from this equation if the molar proportion of A- to HA and the pK a of HA are known.  Conversely, the pK a of an acid can be calculated if the molar proportion of A- to HA and the pH of the solution are known.

35. Buffers  An acid-base conjugate pair (such as acetic acid and acetate ion) has an important property: it resists changes in the pH of a solution. In other words, it acts as a buffer. Consider the addition of OH- to a solution of acetic acid (HA):  A plot of the dependence of the pH of this solution on the amount of OH- added is called a titration curve.  there is an inflection point in the curve at pH 4.8, which is the pK a of acetic acid.

36. Titration curve of acetic acid

37. Application of Henderson equation

39. Thank you