Biochemistry I Spring/Summer 2024 Lecture Notes PDF

Biochemistry I Spring/Summer 2024 February 27, 2024 Textbooks: Mark’s Basic Medical Biochemistry 5th Edition And Harper’s Illustrated Biochemistry 30th Edition 3 tests March/April/May This semester: Chemistry basics Biomolecules Acid-Base Rx Hemoglobin/Myoglobin Amino Acids/lipids/carbohy...

Biochemistry I Spring/Summer 2024 February 27, 2024 Textbooks: Mark’s Basic Medical Biochemistry 5th Edition And Harper’s Illustrated Biochemistry 30th Edition 3 tests March/April/May This semester: Chemistry basics Biomolecules Acid-Base Rx Hemoglobin/Myoglobin Amino Acids/lipids/carbohydrates Enzymes: structure and function Carbohydrate Metabolism Adenosine triphosphate Adenosine Adenine The Fed State The Fasted State The basics: 1. Metals and nonmetals (here: nonmetals are in green boxes and blue (halogens) (important nonmetals are H, C, N, O, F, P, S, Cl, Se, Br, I) Important metals, Li, Na, K, Mg, Ca, Fe, Zn) Important to know the basics: 2. Nucleus is composed of protons and neutrons. Protons carry positive charge (+), neutrons are neutral, and electrons surrounding the nucleus are negatively charged (-) 3. Atomic number = the number of Protons, and The number of protons = the number of electrons in a neutral atom Important to know the basics: 4. Atomic weight = of a chemical element is the weighted arithmetic mean of the relative isotopic masses of all isotopes of that element weighted by each isotope's abundance on Earth Important to know the basics: 5. Mass number is atomic weight rounded to the nearest whole number Mass Number – Atomic number = # of neutrons Mass Numbers - How to find Mass Numbers The mass number is established by rounding the atomic weight to the nearest whole number. The Periodic Table with Atomic Mass will give you the atomic weight, or atomic mass, of the elements. The chemical properties of an element are determined by its Atomic Number not its Mass Number which is why atomic numbers are shown on the Periodic table whilst Mass Numbers are not. Mass numbers equal the total number of heavy, or massive, particles in the nucleus. Subtracting the Atomic number from the Mass Number equals the number of neutrons in the nucleus. Mass Numbers = Atomic Weight of Element, rounded to nearest whole number Number of Neutrons = Mass Number - Atomic Number  Atomic number 6 Mass number 12 12-6 = 6 , so there are 6 neutrons in 12C 12C 98.90 % 6 neutrons 13C 1.1 % 7 neutrons 14C < 0.0001% 8 neutrons (small enough to be ignored) 0.9890 (12) + 0.011 (13.00335) = 11.868 + 0.143 = 12.011 amu Oxygen has atomic weight = 15.999 (15.9994) All 3 isotopes of oxygen have atomic number 8, that is eight protons and eight electrons 16 – 8 = 8 neutrons 17 – 8 = 9 neutrons 18 – 8 = 10 neutrons Atomic mass and calculation of molecular weight (formula weight) Water, molecular formula: H2O Molecular weight = 2 (1.0079) + 15.9994 = 18 grams mol-1 Sodium bicarbonate, NaHCO3 Formula weight = 22.9898 + 1.0079 + 12.011 + 3(15.9994) = 84 g mol-1 What is the molecular formula for each molecule? What is the molecular weight of each molecule? L- tryptophan Notice most hydrogens are omitted What is the difference between Hydrogen/proton/hydride ? Aspirin Lauric Acid D-Glucose Estrogen For a 90 kg person who is 70% water….. How many moles of water? How many grams of water? How many water molecules? Solution: 1 mole (mol) = 6.022 × 1023 molecules Water has a density of 1.0 g mL-1 90 kg (0.7)= 63 kg 63 kg ( 1000g/kg) ( mol/ 18 g) = 3,500 mol (6.022 × 1023 molecules / mol) = 2.1 × 1027 molecules  Example moles/molecules/gram conversions: males have about 5.4 million erythrocytes per microliter (µL) of blood, and females have approximately 4.8 million per µL. 75 milliliters of blood per kilogram for men 78 kg European man Figure 3. (a) A molecule of hemoglobin contains four globin proteins, each of which is bound to one molecule of the iron-containing pigment heme. (b) A single erythrocyte can contain 300 million hemoglobin molecules, and thus more than 1 billion oxygen molecules. A fictional use of moles/molecules/grams conversions: 78 kg male 75 mL blood/kg 5.4 million erythrocytes per μL 300 million hemoglobin molecules per erythrocyte I want 3 drug molecules per hemoglobin molecule- how many grams of drug? Please take note of the implied atoms and bonds in the abbreviated structure C10H12O2 Molecular weight = 10(12.011) + 12(1.0079) + 2(15.9994) = 164.11 g mol-1 78 kg male 75 mL blood/kg 5.4 million erythrocytes per μL 300 million hemoglobin molecules per erythrocyte 78 kg(75 mL/kg) (1000 μL/mL)(5.4 × 106 erythrocytes/μL) 300 × 106 hemoglobin/erythrocyte = 9.4 × 1021 hemoglobin × 3 = 2.8 × 1022 drug molecules 2.8 × 1022 drug molecules ( 1 mol /6.022 × 1023 molecules) = 0.046 mol 0.046 mol (164.11 g/mol) = 7.5 grams Simple Organic Molecules- What does all this symbolism mean? What is implied? Estrogen Aspirin Melatonin Ethanol L- tryptophan Adenine Sodium Benzoate Cholesterol Water D-Glucose Sodium Carbonate Lauric Acid  Tissue: water + mixture of covalent and ionic molecules Salts are ionic compounds Metallic bonds (“sea of free electrons”) NaCl, NaHCO3, H2O, CH3CH2OH, CH3CH2ONa, Benzoic Acid, Sodium Benzoate Basic Functional Groups: alcohol, hydroxyl group, amine, carbonyl, carboxylic acid, alkane, alkene, alkyne, aromatic (benzene) (know (especially) where non- bonding electron pairs are located in biomolecules) glycine alanine Glycine-alaninę dipeptide indole Ionic bonds (salts) metal-nonmetal Covalent bonds nonmetal-nonmetal Polar Covalent bonds nonmetal-nonmetal The water molecule The angle is actually 104.5 ° by VSEPR (what causes H atoms to bend into this angle?) Why is water polar? Water forms hydrogen bonds with itself, and molecules bearing OH, carbonyl, and amine groups Hydrogen bond strength 4 – 50 kJ/mol (this is weak compared to ionic or covalent bonds. Ionic bonds are generally stronger stronger The interior of (often > 500 kJ/mol) in bond strength than DNA and covalent bonds (30 – 180 kJ/mol). H bonds are proteins are easily broken and reformed in standing water. hydrophobic Proteins, DNA/RNA are stabilized by hydrogen bonds. 1 kcal = 4184 J, so 34 kcal/mol (4184 J/1 kcal) = 142,256 J/mol = ~ 142 kJ/mol Hydrogen bonding between purines and pyrimidines Hydrogen bonding and non-bonding electron pairs will be critical to understanding protein folding/enzyme function The Catalytic Triad of Chymotripsin Water solvates ionic salts (less H bonding means higher boiling point and lower freezing point) pH and buffer systems Arrhenius model: Arrhenius postulated that acids produce hydrogen ions in aqueous solution, while bases produce hydroxide ions. Brønsted–Lowry model, an acid is a proton (H+) donor, and a base is a proton acceptor Lewis model A Lewis acid is an electron-pair acceptor A Lewis base is an electron-pair donor Autoionization of water Water is an amphoteric substance: it behaves as both an acid and a base Water reacts with itself in an acid–base reaction Kw = [H+] [OH-] = 1 × 10-14 always, pKw = -log Kw = 14 In pure water at 25 °C [H+] = 1 × 10-7 M [OH-] = 1 × 10-7 M pH = -log [H+] pOH = -log [OH-] pH + pOH = 14 [H+] < [OH-] basic [H+] > [OH-] acidic In biochem, we will be concerned with weak acids and weak bases, but it helps to start with a discussion of Strong Acids and strong bases 0.01 M 𝐻+ [𝐶𝑙−] Ka = [𝐻𝐶𝑙] Cl- is the conjugate base and the conjugate base of the strong strong acid HCl and is Exceedingly weak! HCl does not reform! Example pH of a 0.01 M solution of HCl in water is pH = -log (0.01) = 2, pOH = 12, so [OH-] = 10-12 Likewise, strong bases dissociate 100% in water and Kb is large. Kb>>1. The conjugate acid of a strong base is Exceeding weak! 𝑁𝑎+ [𝑂𝐻−] Kb = [𝑁𝑎𝑂𝐻] What’s the pH of a 0.01 M solution of NaOH? pH = 12 Heme Group: Carbon, Hydrogen, Nitrogen, Oxygen (all non metals) Coordinated with ferrous Iron (II), a metal What is the structure of heme in blood at physiological pH = 7.4 ? pKa propionic acid ≈ 4.88 Propionic acid / propionate The 9 essential amino acids are: histidine, isoleucine, leucine, lysine, methionine, phenylalanine, threonine, tryptophan, and valine. The nonessential amino acids are: alanine, arginine, asparagine, aspartic acid, cysteine, glutamic acid, glutamine, glycine, proline, serine, and tyrosine.