The first day of biochemistry fundemental

A introduction of biochemistry

1. CHEM 4311 General Biochemistry I Spring, 2018 Tuesday/Thursday 9:30 am – 11:00 am. UH 108 Lecture 1 Introduction & Chapter 2 WATER: The Medium of Life Instructor: Dr. Kayunta Johnson-Winters, PhD Phone: [phone] email : [email protected] office: CPB 350

2. Other Considerations. Lecture 1: You should be able to recognize NADPH and ATP. You should also memorize your functional groups found in my lecture 1 notes. Chapter 7: I have decided if I want you to memorize ALL of the sugars in chapter 7 Figure 7.2 and 7.3 just yet, but start with Glyceraldehyde, Fructose, Erythrose , Glucose, Ribose, Galactose , Dihydroxyacetone , and Ribulose (There may be one or two more that isn’t listed here from chapter 7). Chapter 4 amino acids and pKa’s , Chapters 9 & 10 5 nitorgenous bases. You will have to derive the Michaelis-Menten Equation from chapter 13 from memory. You will also have to memorize the Glycolysis Pathway and the TCA cycle. Good Luck to you. May You have a successful semester.

3. Chapter 1 THE FACTS OF LIFE: Chemistry is the Logic of Biological Phenomena This chapter will not be covered in class. You are responsible for the material in chapter 1

4. ABC’s of Biochemistry Macromolecules and their monomeric subunits differ g reatly in size. An alanine molecule is less than 0.5 nm long. A molecule of hemoglobin (the oxygen carrying protein or erythrocytes (red blood cells)), consists of nearly 600 amino acid subunits in four long chains, folded into globular shapes (5.5 nm in diameter). Proteins are much smaller than ribosomes (20 nm in diameter), which are in turn much smaller than organelles such as mitochondria (1000 nm in diameter)

5. ABC’s of Biochemistry FIGURE 1–10b–d The organic compounds from which most cellular materials are constructed: the ABCs of biochemistry. Shown here are (a) six of the 20 amino acids from which all proteins are built (the side chains are shaded pink); (b) the five nitrogenous bases, two five-carbon sugars, and phosphate ion from which all nucleic acids are built; ( c) five components of membrane lipids; and ( d) D -glucose, the simple sugar from which most carbohydrates are derived. Note that phosphate is a component of both nucleic acids and membrane lipids.

6. Amphiphilic Molecules Figure 2.7 (a) Sodium palmitate is an amphiphilic molecule. ( b ) Micelle formation by amphiphilic molecules in aqueous solution . Compounds that contain both hydrophilic and hydrophobic portions are known as Amphiphilic or amphipathic . Fatty acids are a classic biological example. The behaviour of such molecules in solution reflects the their dual water solubility character. The ionic carboxylate hydrates easily while the long tail is intrinsically insoluble.

7. ABC’s of Biochemistry FIGURE 1–11 Structural hierarchy in the molecular organization of cells. The nucleus of this plant cell is an organelle containing several types of supramolecular complexes, including chromatin . Chromatin consists of two types of macromolecules, DNA and many different proteins , each made up of simple subunits.

8. Functional Groups

9. Functional Groups- KNOW THIS Some common functional groups of biomolecules. In this figure And throughout the book, we use R to represent “ any substituent. “

10. ABC’s of Biochemistry Functional Groups Functional groups have chemical properties that are important to the structure and function of the molecules in which they are found. Each functional group holds onto its properties regardless of the molecule in which it is found . Many biomolecules are poly functional , containing two or more types of functional groups, Each with its own chemical characteristics and reactions. The chemical “personality” of a compound is determined by the chemistry of its Functional groups and their disposition in 3D space.

11. ABC’s of Biochemistry Amino – amino acids ( proteins ) | NH2 Carboxyl – amino acids , fatty acids | COOH Hydroxyl – steroids, alcohol, carbohydrates , some amino acids | OH Methyl – may be attached to DNA, proteins, and carbohydrates | CH3 Phosphate – nucleic acids, ATP, attached to amino acid, also in the Phospholipid of the double lipid bilayer. s | PO4 Sulfhydryl – proteins that contain the amino acid cysteine | SH

12. ABC’s of Biochemistry Ester Triacylglycerols are rich in highly reduced carbons and thus yield large amounts of energy in the oxidative reactions of metabolism.

13. ATP All life forms use energy that is stored within the cells to handle biological processes necessary for life . However, a process tends to occur spontaneously only if D G is negative (if free energy is released in the process). Yet, cell function depends largely on molecules , such as proteins and nucleic acids , for which the free energy of formation is positive . To carry out these thermodynamically unfavorable , energy requiring (endergonic) reactions, cells couple them to other reactions to liberate free energy (exergonic reactions), so that the overall process is exergonic : the sum of the free energy changes is negative. The usual source of free energy is in coupled biological reactions is the release of energy b y breakage of phosphoanhydride bonds, such as those found in ATP !!!! i e ; amino acids -  proteins D G 1 is positive (endergonic) ATP -- ADP + P D G 2 is negative (exergonic) THE SUM OF THESE TWO REACTIONS IS NEGATIVE- THE OVERALL PROCESS IS EXERGONIC. Adenosine triphosphate (ATP) is the energy currency of life and it provides that energy for most biological processes by being converted to ADP

14. ATP FIGURE 1–25 Adenosine triphosphate (ATP) provides energy. Here, each P represents a phosphoryl group. The removal of the terminal phosphoryl group (shaded pink) of ATP, by breakage of a phosphoanhydride bond to generate adenosine diphosphate (ADP) and inorganic phosphate ion (HPO 4 2– ), is highly exergonic, and this reaction is coupled to many endergonic reactions in the cell (as in the example in Fig. 1–26b). ATP also provides energy for many cellular processes by undergoing cleavage that releases the two terminal phosphates as inorganic pyrophosphate (H 2 P 2 O 7 2– ), often abbreviated PP i .

15. NADPH Is a coenzyme used in anabolic reactions , such as lipid and nucleic acid synthesis , which require NADPH as a reducing agent. NADPH is the reduced form of NADP + . In plants In chloroplasts, NADP + , is reduced by ferredoxin NADP + reductase in the last step of the electron chain of the light reactions of photosynthesis. The NADPH produced is then used as reducing power for the biosynthetic reactions in the Calvin cycle of photosynthesis. In its energized state, it is NADPH, now holding an extra electron. It is used primarily to create a proton gradient in chloroplasts during the light-dependent reactions. In Animals The oxidative phase of the pentose phosphate pathway is a major s ource of NADPH in cells, producing approximately 60% of the NADPH required.

16. Weak Forces

17. Weak forces maintain biological structure and determine biomolecular interactions AGAIN, THIS INFORMATION IS A REVIEW FROM GENERAL CHEMISTRY! IT IS NOT BIOCHEMISTRY BUT AN IMPORTANT CONCEPT FOR UNDERSTANDING BIOCHEMISTRY. Covalent bonds hold atoms together so that molecules are formed Weak forces profoundly influence the structures and behaviors of all biological molecules Weak forces create interactions that are constantly forming and breaking under physiological conditions Energies of weak forces range from 0.4 to 30 kJ/mol Weak forces include: van der Waals Interactions Hydrogen Bonds Ionic Interactions Hydrophobic Interactions These interactions influence profoundly the nature of biological structures

18. Van der Waals When two uncharged atoms are brought very close together, their surrounding electron cl ouds influence each other. Random variations in the positions of the electrons around one nucleus may create a transient electric dipole , which induces a transient, opposite electric dipole in the nearby atom. The two dipoles weakly attract each other bringing the two nuclei closer. These weak attractions are called van der Waals interactions . As the two nuclei draw closer together, their electron clouds begin to repel each other. At the point where the net attraction is maximal, the nuclei are said to be in Van der Waals contact . https :// www.youtube.com / watch?v =HGc9RFD7iSE

19. Hydrogen Bond A hydrogen bond is the attractive interaction of a hydrogen atom with an electronegative atom such as a N, O or F from another molecule or chemical group. The hydrogen must be covalently bonded to another electronegative atom to create the bond. These bonds can occur between molecules ( intermolecularly ), or within different parts of a single molecule ( intramolecularly ) . This type of bond occurs in both inorganic molecules such as water and organic molecules such as DNA.

20. Ionic Bonding An ionic bond is a type of chemical bond formed through an electrostatic attraction between two oppositely charged ions. Ionic bonds are formed between a cation, which is usually a metal, and an anion, which is usually a nonmetal. i e Na + and Cl -

21. Weak forces include: van der Waals Interactions: 0.4-4.0 kJ/mol Hydrogen Bonds: 12-30 kJ/mol Ionic Interactions: 20 kJ/mol Hydrophobic Interactions: <40 kJ/mol These interactions influence profoundly the nature of biological structures

22. Polar vs Nonpolar Polar molecule - a molecule in which the polar bonds are disposed in such a way that it imparts an asymmetry to the molecule as a whole. That is , it gives the whole molecule a Dipole Moment : example: water H-O-H has two polar bonds. Since this molecule is Bent, those two polar bonds ADD TOGETHER to produce a molecule with a dipole moment. That is, a polar molecule. Non polar example: carbon dioxide O=C=O has two polar bonds also. Since this molecule is Linear, those two polar bonds ADD TOGETHER to cancel each other out, to produce a molecule with NO dipole moment. That is, a nonpolar molecule.

23. Water: The Medium of Life Chapter 2 Again, Chapter 2 is NOT biochemistry , but should be review material for you. You are responsible for the material for the exam. pH and buffers are linked to amino acids in Chapter 4. We will Focus on this in Chapter 2

24. Outline What are the properties of water? What is pH ? What are buffers , and what do they do? Does water have a unique role in the fitness of the environment?

25. What is pH? The pH scale is a simple method that avoids the use of negative exponents . Sørensen devised the pH scale which is simply an expression of ionization over 14 orders of magnitude. His definition was that pH is the negative log of the H + ion concentration. i e pH = - log[H + ] (Note [H + ] = 10 -pH ) The pH scale is particularly useful in biological solutions where the H + ion concentration is critically important and typically low . Often the concentration is in the realm of 1 x10 –7 M or in pH terms pH = 7. Eg Normal Blood Plasma = pH 7.4 (H + = 0.00000004 M ) Under certain disease states the pH can be as low as pH 6.8 (0.00000016 M H + ) Four times higher than normal. NOTE: It is important to be familiar with logarithms

26. What is pH? I WILL ASSUME THAT KNOW LOGARITHMS AND EXPONENTS.

27. What is pH? Lehninger

28. What is pH ? Acid/Base Concepts: An acid is a substance that has H in its formula and dissociates in water to yield H 3 O + . A base is a substance that has OH in it’s formula and dissociates in water to yield OH - . HA represents the acid and A − is the conjugate base. The equilibrium constant K is an expression of the equilibrium concentrations o f the molecules or the ions in solution. K a = [H + ][A - ]/[HA]

29. What is pH ? Acid/Base Concepts: Brønsted acids and Brønsted bases are defined Acid is a molecule or ion that is able to lose, or “donate” a hydrogen cation (proton, H + ) Base is a species that is able to gain or “accept” a hydrogen cation (proton)

30. Hendelson Hasselbach Equation If we consider a weak acid K a = [H + ][A - ]/[HA] Rearranging for H + [H + ] = K a [HA ]/[A-] Taking the log of both sides gives log[H + ] = logK a + log [HA]/[A - ] Changing sign and defining pK a as – logK a pH = pK a - log [HA]/[A - ] or pH = pK a + log [A - ]/[HA] This is known as the Henderson- Hasselbach Equation. KNOW THIS EQUATION !!!! The pH of a solution can be calculated provided K a and the concentrations of the weak acid and its conjugate base are known. NB When [A - ] = [HA] pH = pK a

31. Hendelson Hasselbach Equation Essentially you can use the HH eqn in three different ways: 1 - you know the pH and the pKa and you want to find [A-] / [HA] 2 - you know the pKa and [A - ] / [HA] and want to find the pH 3 - you know the [A - ] / [HA] and pH and want to find the pKa

32. What is pH ? Titration Curves Titration is an analytical method used to determine how much acid is in solution. A measured volume of the acid solution is titrated by slowly adding a strong base (typically NaOH ) of known concentration. A plot of the pH vs the equivalents of base added is the titration curve . For example the titration of CH 3 COOH ( HAc ). Fig 2.11

33. What is pH ? When the titration begins we have mostly CH 3 COOH and some CH 3 COO - and H + Two Reactions are in effect CH 3 COOH <-> H + + CH 3 COO - K a = 1.74x10 -5 OH - + H + -> H 2 O K eq = [H 2 O]/K w = 5.55 x 10 15 Note that the second reaction is strongly favored (having an Keq Greater than 10 15 . NaOH addition thus neutralizes the H + ions. As H+ is neutralized, the equilibrium is perturbed and more CH 3 COOH dissociates to CH 3 COO - and H + The pH gradually increases and CH 3 COO - accumulates When half the concentration of CH 3 COOH has been neutralized, 0.5 equivalents of OH - have been added, pH = pKa . pKa values thus lie at the midpoint of the titration curve

34. What is pH ? Figure 2.12 The titration curves of several weak acids. The shapes of the titration curves of weak electrolytes are identical. Note, that the midpoint potentials of the different curves vary in a way that characterizes the particular electrolytes. HAc pK a =4.76 Imidazole pK a =6.99 Ammonium pK a = 9.25

35. 39 H 3 PO 4 ( trihydrogen phosphate) has three dissociable protons ( polyprotic ). Thus three equivalents of OH- are required to titrate (neutralize) this acid. The protons come off in distinct phases. Each proton thus has a distinct pK a value. pK 1 = 2.15 pK 2 = 7.2 pK 3 = 12.4 At what pH’s is phosphoric acid a good buffer ? Figure 2.13 The titration curve for phosphoric acid.

36. pK a Rule of Thumb >1 pH unit below the pK a ~ fully protonated >1 pH unit above the pK a ~ fully deprotonated What is pH ?

37. Outline What are the properties of water? What is pH? What are buffers, and what do they do? Does water have a unique role in the fitness of the environment?

38. What are buffers, and what do they do? Buffers are solutions that resist changes in pH as acid and base are added Most buffers consist of a weak acid and its conjugate base A solution of a weak acid that has a pH nearly equal to its pK a , contains an amount of the conjugate base nearly equivalent to the weak acid. This region of the titration curve is relatively flat (Fig 2.14). Addition of H + has little effect because it is absorbed by the following reaction: H + + A - HA Similarly, any increase in [OH-] is offset by the process: OH - + HA A - + H 2 O Thus, the pH remains relatively constant. Buffers can only be used reliably within a pH unit of their pK a Figure 2.14 A buffer system consists of a weak acid, HA and its conjugate base, A -

39. Additional Questions ??? What are the properties of water? What is pH? What are buffers, and what do they do? Does water have a unique role in the fitness of the environment? – you should have read on your own Suggested Text Problems: Chapter 2, Page 49 for 5 th edition # 1-4, 13, 15-17 6 th edition page 50 . # 1-4, 13, 15- 17 These type of questions could come in essay form or as a multiple question problem.

40. What are the properties of water? Water Can Ionize to Form H + and OH - 44 Water ionizes because the larger, strongly electronegative oxygen atom strips the electron from one of it’s hydrogen atoms, leaving the proton to dissociate: H 2 O -> OH - + H + Two ions are thus formed: 1) protons or hydrogen ions , H+, and 2) hydroxyl ions , OH-. Free protons are immediately hydrated to form hydronium ions , H3O+ : H + + H 2 O -> H 3 O + Most hydrogen atoms in liquid water are hydrogen bonded to a neighboring water molecule, this protonic hydration is an instantaneous process and the ion products of Water are H 3 O + and OH - .