GENERAL BIOCHEMISTRY Dr. Dina Abed Bakhotmah dbakhotmah@kau.edu.sa With thanks and respect to Dr. Khadijah Saeed Balamash Textbook & References Textbook: • Voet & Voet: Biochemistry, Wiley & Sons Inc. New York References: • Richard A. Harvey & Denise R. Ferrier : Biochemistry (Lippincott's Illustrated Reviews) Content General Biochemistry (Bioc 201) Contents I-Introduction: 1- Definition 2- Biological Structures 3- Chemical bonds 4- Properties of water II- Carbohydrates 1- Monosaccharides 2- Disaccharides 3- Polysaccharides 4- Digestion of carbohydrates III- Amino acids 1- Structures and general properties 2- Peptide bonds 3- Classifications and characteristics 4- Acidic basic properties IV- Proteins 1- Primary structures 2- Secondary structures 3- Tertiary structures 4- Quaternary structures V- Lipids and Membranes 1- Lipid classification 2- Properties of lipid aggregates 3- Biological membranes 4- Membrane assembly and protein targeting 5- Lipoproteins VI- Nucleotides and Nucleosides and Bases 1- The chemical structures of DNA and RNA VII- Introduction to 1- Enzymes 2- Hormones 3- Vitamins Exams: • First exam 15 marks • Midterm Exam • Lab 25 marks • Final Exam 40 20 marks CHAPTER 1 Introduction: 1- Definition 2- Biological Structures 3- Chemical bonds 4- Properties of water What is Biochemistry? -1 • Biochemistry is the chemistry of the living organisms or life. • Biochemistry deals with: chemistry, structure, organization, and function of living matter. Principle Areas of Biochemistry • Structure and function of biological macromolecules • Metabolism – anabolic and catabolic processes. • Molecular Genetics – How life is replicated. Regulation of protein synthesis Origins of Biochemistry: Famous Dead Biochemist! Fallacy #1: Biochemicals can only be produced by living organisms •Dead Biochemist #1 •1828 Friedrich Wohler Fallacy #2: Complex bioconversion of chemical substances require living matter Dead Biochemists #2 •1897 Eduard Buchner Glucose + Dead Yeast = Alcohol Fallacy #2: Complex bioconversion of chemical substances require living matter Dead Biochemists #3 Emil Fischer • Cell Theory-1 • Cell is the smallest unit of living matter. (Don’t confuse this with electrons, atoms, proteins, DNA, etc.,These are lifeless molecules) • Cell is the structural & functional unit of all organs and/or organisms made up of thousands of different types of molecules in highly organized selfassembled structures. . Cell Theory-2 • All organisms are composed of one or more types of cells. • All cells come from preexisting cells by division. • Spontaneous generation does not occur. • Cell is capable of reproduction. Cell Theory-3 • Cells contains hereditary information which is passed from cell to cell during cell division. • Most biochemical reactions (but not all!) take place within cells Typical Cells • Cells come in a variety of shapes, structures, and sizes. • They are usually divided into two broad groups: Eukaryotes and Prokaryotes. Eukaryotic cells (Eu = true; kary = nucleus): have a membranebound nucleus and a variety of organelles and internal membranes. Prokaryotic cells • Prokaryotic cells (Pro = before) are smaller and lack much of the internal compart-mentalization and complexity of eukaryotic cells; No membrane-bound nucleus or other organelles. Viruses • Viruses do not always conform to cell theory: one or more of the basic cell components is missing. Inside the host cell, viruses are living matters. Sizes and Shapes of Cells Organization of Life • • • • • • • Elements (C, H, O, N) Simple organic compounds (monomers) Macromolecules (polymers) Supramolecular structures (DNA, Lipids) Organelles Cells Tissues (Epithelia, Connective, Muscle, Nerve Tissue) • Organs (Heart, skin, kidney, etc.) • Organisms (Human, bovine, etc) Chemical Elements of Life • The cell is a COMPLEX CHEMICAL FACTORY containing some of the same elements found in the nonliving environment. • Chemical elements of a living cell are the same as in the Earth’s crust, but in different proportions. • CHNOPS: are the most abundant elements in cell. • They account for more than 99% of atoms in the human body Chemical Elements of Life • H, O, N and C have common properties that are important to the chemistry of life. They all: have relatively low atomic numbers. capable of forming one, two, three and four bonds (for H, O, N and C , in order). form the strongest covalent bonds in general. TWO TYPES OF COMPOUNDS • Organic - Contain C, H, and O in some ratio (usually referred to as chemicals of life) – Carbohydrates, Proteins, Lipids, Nucleic Acids • Inorganic - usually "support" life - no specific ratio of C, H, and O – Water (H2O), Carbon Dioxide (CO2) Organic Chemistry • What makes Carbon Special? Why is Carbon so different from all the other elements on the periodic table? • The answer derives from the ability of Carbon atoms to bond together to form long chains and rings. Organic Chemistry Organic Chemistry Carbon can covalently bond with up to four other atoms. Carbon can form immensely diverse compounds, from simple to complex. Methane with 1 Carbon atom DNA with tens of Billions of Carbon atoms Many Important Biomolecules are Polymers • Biopolymers - macromolecules created by joining many smaller organic molecules (monomers) • Condensation reactions join monomers (H2O is removed in the process) • Residue - each monomer in a chain 32 Common theme: Monomers form polymers through condensations Polymers are broken down through hydrolysis. Many Important Biomolecules are Polymers monomer polymer supramolecular structure Carbohydrades nucleic acids lipids proteins fatty acid amino acid glucose nucleotide phospholipid protein subunit cellulose DNA membrane protein complex cell wall chromosome There are relatively few species of monomeric units that occur in each class of biological macromolecule • Proteins – Are all synthesized from the same 20 species of amino acids Nucleic acids Are made from 8 types of nucleotides 4 each in DNA and RNA • Polysaccharides are ~8 commonly occurring types of sugar in polysaccharides. 1. Where in a eukaryotic cell, DNA can be found? A. Nucleus B. Mitochondrion C. Vacuole D. Both (a) and (b) 2-The major elements in a human are C, H and Si True False 3- In a human cell the nucleus and mitochondria and many other cell organelles have membranes surrounding them. True False 4- Discribe the Cell Theory. 1.Cells are the smallest unit of life 2.All Cells come from previously existing cells 3.All living things are composed of cells 5- Name an example of an organ. Heart kidney 6- Name several types of tissues Muscle Nerve Tissue Chemical Bonds COVALENT BONDING non-polar covalent And polar covalent IONIC BONDING Chemical Bonds • Covalent bonds – Strong – Hold the atoms in an individual molecule together • Noncovalent bonds – Determine the three-dimensional architecture of large biological molecules and molecular complexes – Weaker more easily broken • No one bond is strong, the effect of many weak bonds functioning together can be very powerful COVALENT BONDING SHARING IS CARING! The outer electron shell of each atom has a characteristic number of electrons: . . .. H . C . . . N . . .. . P. . .. . O . .. .. . S . .. These atoms readily form covalent bonds with other atoms and rarely exist as isolated entities As a rule: • Each type of atom forms a characteristic number of covalent bonds with other atoms. • A hydrogen atom: with one electron in its other shell, forms only one bond. • A carbon atom: with four electrons, generally forms four bonds, as in methane (CH4): H .. H :C: H .. H or • Nitrogen and phosphorus have five electrons in their outer shells. – These atoms can form either • Three covalent bonds, as in ammonia (NH3) • Five, as in phosphoric acid (H3PO4) • Oxygen and Sulphur contain six electrons in their outermost shells. – These atoms can forms only two covalent bonds • In molecular oxygen (O2) • Hydrogen sulphide (H2S) O::O or • A sulphur atom can – Form as many as six covalent bonds • Sulphur trioxide (SO3) • Sulphuric acid (H2SO4) • Covalent bonds between different atoms are generally dipolar: – Because one of the atoms is usually more electronegative than the other. • When a dipolar bond breaks: – The bonding electrons often stay with the more electronegative atom, which then becomes a negatively charged ion, or an anion – The other part of the molecule becomes a positively charged ion, or a cation. Electronegativity decreases as you move down each column. Electronegativity increases as you move from left to right. IONIC BONDS • Occur when 1 or more electrons are TRANSFERRED from one atom to another. • When an atom loses an electron it is a POSITIVE charge. • When an atom gains an electron it is a NEGATIVE charge • These newly charged atoms are now called IONS – Example: NaCl (SALT) Ionic bonds • The ionic bonds result from the attraction of a positive charge for a negative charge. • Ionic bond do not have fixed or specific geometric orientations – Because the electrostatic field around an ion. Its attraction for an opposite charge. Is uniform in all directions. – Unlike covalent or hydrogen bonds In some compounds the atoms are so different in electronegativity: That the bonding electrons are always found around the more electronegative atom – That is, the electrons are never shared. • Because electrons are not shared, – The bonds in such compounds cannot be covalent • In sodium chloride (NaCl) for example: – The bonding electron contributed by the sodium atoms is completely transferred to the chlorine atoms – Even in solid crystals of NaCl, the sodium and chlorine atoms are ionized, so it is more accurate to write the formula for the compound as Na+ Cl- The hydrogen bond • A hydrogen atom normally forms a covalent bond with only one other atom (D) at a time. • A covalently bonded hydrogen atom may form an additional bond with another atom (A): – A hydrogen bond: • Is a weak association between an electronegative atom (A) (the acceptor atom) and a hydrogen atom covalently bonded to another atom (D) (the donor atom). Hydrogen Bonds • hydrogen bond donor :to which hydrogen is covalently bonded • hydrogen bond acceptor : with the nonbonded electron pair The hydrogen bond in water is a classic example: A hydrogen atom in one molecule is attracted to a pair of electrons in the outer shell of an oxygen atom in an adjacent water molecule. Van der Waals Interactions • When two atoms approach one another closely, they create: – A nonspecific Weak attractive force that produces a van der Waals interaction – Named for Dutch physicist Johannes Diderik van der Waals (1837-1923), who first described it. Van der Waals Interactions If two noncovalently bonded atoms are close enough together: – The transient dipole in one atom will perturb (disturb) the electron cloud of the other. – This perturbation generates a transient dipole in the second atom – The two dipoles will attract each other weakly. Example d+ H Cl d- A DIPOLE (it’s polar) - e- e e- e- ee- e- ee- - e -e e e - - e- ee e d+ e- Ar non-polar INDUCED DIPOLE Dipole – Induced Dipole (weak and short-lived) d- Van der Waals Interactions • All types of molecules, both polar and nonpolar exhibit van der Waals interactions – They are responsible for the cohesion (pulling together) among molecules of nonpolar liquids and solids: Van der Waals Interactions • Attraction decreases rapidly with – Increasing distance and is effective only when atoms are quite close to one another. • If atoms get too close together: – They become repelled by the negative charges in their outer electron shells. • The van der Waals interaction is even weaker than the hydrogen bond Properties of Water-1 • • • • Adhesion Cohesion high surface tension holds heat to regulate temperature (High heat capacity) • less dense as a solid than a liquid PRORERTIES OF WATER-2 • The H2O molecule has a bent geometry – With an O — H bond distance of 0.958 Å – An H — O — H bond angle of 104.5°. PRORERTIES OF WATER-3 • Water molecules Associate through Hydrogen bonds • The electrostatic attractions between the dipoles of two water molecules tend to orient them such that – The O — H bond on one water molecule points toward a lonepair electron cloud on the oxygen atom of the other water molecule. • This results in a directional intermolecular association known as hydrogen bond: – An interaction that is crucial both to the properties of water itself and to its role as a biochemical solvent. PRORERTIES OF WATER-4 • The large electronegativity difference between H and O confers a 33 % ionic character on the O — H bond • As water is clearly a highly polar molecule, a phenomenon with enormous implications for living system. • The energy of a hydrogen bond (~ 20 kj. mol-1 in H2O) is small compared to Covalent bond energies (for instance, 460 kj. Mol-1 for an O — H covalent bond). Properties of Water-5 Water is less dense as a solid! This is because the hydrogen bonds are stable in ice – each molecule of water is bound to four of it’s neighbors. Water as a solvent • Solubility: depends on the ability of a solvent to interact with a solute more strongly than solute particles interact with each other. • Water is said to be the “universal solvent.” • The polar character of water makes it an: – Excellent solvent for polar and ionic materials, which are therefore said to be hydrophilic (Greek: hydor, water + philos, loving). AQUEOUS SOLUTION • Life, as we know it, occurs in aqueous solution. • Water is a chemically reactive liquid with such extraordinary physical properties. • The structures of the molecules on which life is based (proteins, nucleic acids, lipids, and complex carbohydrates) Result directly from their interactions with their aqueous environment. In aqueous solutions: • Simple ions of biological significance, such as Na+ , K+ , Ca2+ , Mg2+ , and Cl-: – Do not exist as free, isolated entities. – Instead, each is surrounded by a stable, tightly held shell of water molecules – Primary interaction occurs between the ion and the oppositely charged end of the water dipole • Ions play an important biological role when they pass through: – Narrow pores – Channels – In membranes • Ionic movements through membranes are Essential for the – Conduction of nerve impulses – Stimulation of muscle contraction • Molecules with dipolar bonds also can attract water molecules, as can molecules that easily form hydrogen bonds – Such polar molecules can dissolve in water and are said to be hydrophilic (from the Greek for “water- loving”). • Typical chemical groups that interact well with water are: –Hydroxyl – OH –Amino – NH2 –Peptide bond –Ester bond Hydrophobic Interactions • Nonpolar molecules: – Contain neither ions nor dipolar bonds – Do not become hydrated. Because they are insoluble in water, they are said to be hydrophobic (from the Greek for “waterfearing”). • The covalent bonds between two carbon atoms and between carbon and hydrogen atoms – Are the most common nonpolar bonds in biological system. Hydrophobic Interactions • Hydrocarbons – molecules made up only of carbon and hydrogen — are virtually insoluble in water. • The force that causes hydrophobic molecules or nonpolar portions of molecules to aggregate rather than to dissolve in water is called hydrophobic interaction. Hydrophobic Interactions • A nonpolar molecule cannot form hydrogen bonds with water: – So it distorts the usual water structure – Forcing the water to make a cage of bonds around it, but not with it. • On the other hand, nonpolar molecules bond together comfortably through van der Waals interactions The result is: – A very powerful tendency for hydrophobic molecules to bond together and – Not dissolve in water. • Small hydrocarbons such as butane CH3—CH2—CH2—CH3 – Are slightly soluble in water: • Because they can dissolve without disrupting the water lattice (net) significantly. • 1-butanol mixes completely with water in all proportions CH3—CH2—CH2—CH2OH – Thus the replacement of just one hydrogen atom with the dipolar—OH group allows the molecule to form hydrogen bonds with water and greatly increases its solubility. • Multiple noncovalent bonds can contribute to the stability of large biological molecules • These interactions can also confer specificity by determining how molecules will fold or which regions of different molecules will bind together • Several different weak bonds and interactions can bind two protein chains together. B. Water as a solvent • • • Solubility: depends on the ability of a solvent to interact with a solute more strongly than solute particles interact with each other. Water is said to be the “universal solvent.” The polar character of water makes it an: – Excellent solvent for polar and ionic materials, which are therefore said to be hydrophilic (Greek: hydor, water + philos, loving). • Nonpolar substances are – Insoluble in water (“oil and water don’t mix”) and are described as being hydrophobic (Greek: phobos, fear). – Soluble in nonpolar solvents such as • CCl4 or hexane. • This information is summarized by another maxim. “like dissolves like.” 1- The formation of large molecules from small repeating units is accomplished by a(n) ______ reaction. A. B. C. D. E. oxidation reduction dehydration Hydrolysis decarboxylation 2- Which force is most important in allowing ammonia, NH3, to dissolve in water? A. B. C. D. E. hydrogen bonding dipole-induced dipole ion-dipole dipole-dipole ionic 3- Which one of the following species contains a polar covalent bond? A. oxygen B. carbon dioxide C. sodium chloride D. magnesium fluoride E. helium 4- What happens when a covalent bond is formed? A. Electrons are transferred from one atom to another B. Electrons are shared between two atoms C. Protons are transferred from one atom to another D. Protons are shared between two atoms 5- Water (H2O) has a bent shape, resulting in an unequal distribution of the electrons. Oxygen, which is more electronegative than the hydrogens, has a greater pull on the electrons, giving the oxygen a partial negative charge and the hydrogens a partial positive charge. This unequal distribution is called a: A. B. C. D. Covalent bond Tail Bent geometry Dipole 6-Which of the following BEST describes the “bonds” holding liquid water molecules together? A. Ionic. B. Covalent. C. Adhesion. D. Hydrogen.