Chapter 1: Biochemistry: An Evolving Science PDF

CHAPTER 1: BIOCHEMISTRY: AN EVOLVING SCIENCE  Biochemistry is the study of the chemistry of life processes  The first synthesis of urea from ammonium cyanate In 1828, the German chemist Friedrich Wöhler obtained urea by treating silver isocyanate with ammonium chloride F...

CHAPTER 1: BIOCHEMISTRY: AN EVOLVING SCIENCE  Biochemistry is the study of the chemistry of life processes  The first synthesis of urea from ammonium cyanate In 1828, the German chemist Friedrich Wöhler obtained urea by treating silver isocyanate with ammonium chloride For many historians this marks the beginning of biochemistry  Our knowledge of biochemistry has been applied to solve problems in medicine, dentistry, agriculture, forensics, environmental sciences, and many other fields  1.1 BIOCHEMICAL UNITY  DIVERSE BIOCHEMICAL WORLD  Animal kingdom Nearly microscopic insects Elephants and whales  Plant kingdom Small and relatively simple algae Large and complex giant sequoias  Microscopic world Single-celled organisms: bacteria and yeast Present with great diversity in water, in soil, and on or within larger organisms Some organisms can survive in hot springs and glaciers  1.1 BIOCHEMICAL UNITY  COMMON FEATURES IN ALL ORGANISMS  Large organisms are built up of cells resembling single-celled microscopic organisms  Life processes use two different classes of molecules Macromolecules such as proteins and nucleic acids Metabolites such as glucose and glycerol  Deoxyribonucleic acid (DNA) and proteins DNA stores genetic information in all cellular organisms Proteins are key participants in most biological processes; they are built from the same set of 20 building blocks; they have similar roles and similar three-dimensional structures  1.1 BIOCHEMICAL UNITY  COMMON FEATURES IN ALL ORGANISMS Fig 1.1 Biological diversity and similarity. The shape of a key molecule in gene regulation (the TATA-box-binding protein) is similar in three very different organisms that are separated from one another by billions of years of evolution.  1.1 BIOCHEMICAL UNITY  COMMON METABOLIC PROCESSES  Conversion of glucose and oxygen into CO2 and water Identical in simple bacteria such as Escherichia coli (E. coli) and human beings  Photosynthesis vs the breakdown of carbohydrates The biochemical processes by which plants capture light energy and convert it into more-useful forms are similar to steps used in animals to capture energy released from the breakdown of glucose.  These observations suggest: All living things have a common ancestor; modern organisms have evolved from this ancestor into their present forms  1.1 BIOCHEMICAL UNITY  COMMON METABOLIC PROCESSES Fig 1.2 A possible time line for biological evolution. Selected key events are indicated. Note that life on earth began approximately 3.5 billion years ago, whereas human beings emerged quite recently.  1.1 BIOCHEMICAL UNITY  THE THREE OF LIFE  On the basis of their biochemical characteristics, the diverse organisms of the modern world can be divided into three fundamental gruops Eukarya, Bacteria, and Archaea Fig 1.3 The tree of life. A possible evolutionary path from a common ancestor approximately 3.5 billion years ago at the bottom of the tree to organisms found in the modern world at the top.  1.2 DNA: FORM AND FUNCTION  HISTORY OF DNA RESEARCH  Friedrich Miescher was a Swiss physician and biologist who first isolated nucleic acid in 1869 in the pus of discarded surgical bandages; as it resided in the nuclei of cells, he called it "nuclein".  In 1878, Albrecht Kossel isolated the non-protein component of "nuclein", nucleic acid, and later isolated its five primary nucleobases.  In 1919, Phoebus Levene identified the base, sugar and phosphate nucleotide unit. Levene suggested that DNA consisted of a string of nucleotide units linked together through the phosphate groups.  1.2 DNA: FORM AND FUNCTION  HISTORY OF DNA RESEARCH  In 1928, Frederick Griffith discovered that traits of the "smooth" form of the Pneumococcus could be transferred to the "rough" form of the same bacteria by mixing killed "smooth" bacteria with the live "rough" form. This system provided the first clear suggestion that DNA carries genetic information—the Avery–MacLeod–McCarty experiment— when Oswald Avery, along with coworkers Colin MacLeod and Maclyn McCarty, identified DNA as the transforming principle in 1943  In 1937 William Astbury produced the first X-ray diffraction patterns that showed that DNA had a regular structure.  1.2 DNA: FORM AND FUNCTION  HISTORY OF DNA RESEARCH  DNA's role in heredity was confirmed in 1952, when Alfred Hershey and Martha Chase in the Hershey–Chase experiment showed that DNA is the genetic material of the T2 phage.  In 1953, James D. Watson and Francis Crick suggested what is now accepted as the first correct double-helix model of DNA structure in the journal Nature. …  1.2 DNA: FORM AND FUNCTION  HISTORY OF DNA RESEARCH  Their double-helix, molecular model of DNA was then based on a single X-ray diffraction image taken by Rosalind Franklin and Raymond Gosling in May 1952, as well as the information that the DNA bases are paired — also obtained through private communications from Erwin Chargaff in the previous years.  In 1962, after Franklin's death, Watson, Crick, and Wilkins jointly received the Nobel Prize in Physiology or Medicine. However, Nobel rules of the time allowed only living recipients, but a vigorous debate continues on who should receive credit for the discovery.  1.2 DNA: FORM AND FUNCTION  FOUR BUILDING BLOCKS OF DNA  DNA is a linear polymer made up of four different types of monomers  It has a fixed backbone, which is built of repeating sugar- phosphate units.  Each sugar is connected to two phosphate groups through different linkages; each DNA strand has directionality. Fig 1.4 Covalent structure of DNA.  1.2 DNA: FORM AND FUNCTION  FOUR BUILDING BLOCKS OF DNA  There are four bases joined to each deoxyribose; adenine (A), cytosine (C), guanine (G), and thymine (T)  Each monomer of DNA consists of a sugar-phosphate unit and one of four bases attached to the sugar. Four bases found in DNA  1.2 DNA: FORM AND FUNCTION  DOUBLE HELIX FORMATION  Most DNA molecules consist of not one but two strands.  The sugar-phosphate backbone lies on the outside and the bases on the inside.  The bases form specific base pairs (bp) held together by hydrogen bonds: A-T and G-C. Fig 1.5 The double helix. Fig 1.6 Watson-Crick base pairs.  1.2 DNA: FORM AND FUNCTION  IMPORTANCE OF DNA STRUCTURE  The structure is compatible with any sequences of bases. The base pairs have the same shape and thus fit equally well into the center of DNA The DNA sequence determines the sequences of the ribonucleic acid (RNA) and protein molecules.  The sequence of bases along one strand completely determines the sequence along the other strand. Each strand can act as a template for the generation of its partner strand. Fig 1.7 DNA replication. 1.3 CHEMICAL CONCEPTS  Concepts from chemistry explain the properties of biological molecules.  The concepts include: The types of chemical bonds The structure of water, the solvent in which most biochemical processes take place The First and Second Laws of Thermodynamics The principles of acid-base chemistry  1.3 CHEMICAL CONCEPTS  DOUBLE HELIX FORMATION  Two short DNA strands which were chemically synthesized to have complementary sequences form a double helix with Watson-Crick base pairs  To explain this spontaneous change, we must consider several factors: The types of interactions The types of bonds The energetic favorability The influence of the solution conditions Fig 1.8 Formation of a double helix.  1.3 CHEMICAL CONCEPTS  COVALENT AND NONCOVALENT BONDS  Covalent and noncovalent bonds are important for the structure and stability of biological molecules  Covalent bonds Formed by the sharing of a pair of electrons between adjacent atoms Strong bonds A typical C−C bond: 1.54 Å , 355 kJ/mol (85 kcal/mol) C=C bond: 1.34 Å , 614 kJ/mol Resonance structures 1.40 Å  1.3 CHEMICAL CONCEPTS  NONCOVALENT INTERACTIONS  Weaker than covalent bonds but crucial for biochemical processes  Electrostatic interactions Interactions between charged molecules Coulomb’s law E = kq1q2 / Dr D: dielectric constant Dielectric constant, 80 for water and 2 for hexane; therefore the dielectric constant of the medium affects electrostatic interactions significantly  1.3 CHEMICAL CONCEPTS  NONCOVALENT INTERACTIONS  Hydrogen bonds Responsible for specific base-pair formation in the DNA double helix Much weaker than covalent bonds (4−20 kJ/mol) Longer than covalent bonds (1.5 Å−2.6 Å) ◄ Fig 1.9 Hydrogen bonds.  1.3 CHEMICAL CONCEPTS  NONCOVALENT INTERACTIONS  van der Waals interactions The temporary dipole on one atom can induce a similar temporary dipole on an adjacent atom Weak interactions (2−4 kJ/mol), but for large molecules they can be substantial  1.3 CHEMICAL CONCEPTS  PROPERTIES OF WATER  Most biochemical reactions take place in water  Its properties are essential to the formation of macromolecular structures and the progress of chemical reactions  Water is a polar molecule  Water is highly cohesive because of hydrogen bonds Water interacts with molecules through hydrogen bonds and through ionic interactions  1.3 CHEMICAL CONCEPTS  PROPERTIES OF WATER paraffin water  The density of liquid water and ice Liquid water 1.00 g/ml, ice 0.917 g/mL at 0 ˚C  1.3 CHEMICAL CONCEPTS  THE HYDROPHOBIC EFFECT  The hydrophobic effect is the observed tendency of nonpolar substances to aggregate in aqueous solution and exclude water molecules Fig 1.12 The hydrophobic effect. The aggregation of nonpolar groups in water leads to the release of water molecules, initially interacting with the nonpolar surface, into bulk water.  1.3 CHEMICAL CONCEPTS  INTERACTIONS IN THE DOUBLE HELIX  Electrostatic interactions of negatively charged phosphate groups Unfavorable electrostatic interactions when two strands of DNA come together These phosphate groups are far apart (10 Å ) to minimize the repulsion Water (high dielectric constant), and ions (Na+ and Mg2+) diminish the repulsion Fig 1.13 Electrostatic interactions in DNA.  1.3 CHEMICAL CONCEPTS  INTERACTIONS IN THE DOUBLE HELIX  1.3 CHEMICAL CONCEPTS  INTERACTIONS IN THE DOUBLE HELIX  Hydrogen bonds are important in determining the formation of specific base pairs in the double helix  π-π stacking is also an important interaction in the double helix The typical separation between the planes of base pairs is 3.4 Å. Fig 1.14 base stacking.  1.3 CHEMICAL CONCEPTS  THE LAWS OF THERMODYNAMICS  The first law of thermodynamics Energy cannot be created nor destroyed. Therefore, the total energy of the universe is a constant. Energy can, however, be converted from one form to another or transferred from a system to the surroundings or vice versa.  1.3 CHEMICAL CONCEPTS  THE LAWS OF THERMODYNAMICS  The second law of thermodynamics The entropy of the universe increases for spontaneous processes, and the entropy of the universe does not change for reversible processes. For reversible processes: Suniv = Ssystem + Ssurroundings = 0 For irreversible processes: Suniv = Ssystem + Ssurroundings > 0 These last truths mean that as a result of all spontaneous processes the entropy of the universe increases.  1.3 CHEMICAL CONCEPTS  Entropy Changes in Surroundings  Heat that flows into or out of the system changes the entropy of the surroundings.  For an isothermal process: qsys Ssurr = T  At constant pressure, qsys is simply H for the system.  1.3 CHEMICAL CONCEPTS  Gibbs free energy G = H  TS, G = H  TS [Eq. 1] qsystem Since Ssurroundings = T and qsystem = Hsystem This becomes: Hsystem Suniverse = Ssystem + T Multiplying both sides by T, we get TSuniverse = Hsystem  TSsystem TSuniverse = G by comparing with Eq 1  1.3 CHEMICAL CONCEPTS  THE FORMATION OF THE DOUBLE HELIX  The formation of a double helix from two single strands results in a decrease in the entropy of the system  Heat should be released not to violate the second law of thermodynamics  A substantial amount of heat is released in the process (approximately 250 kJ / mol) G = H  TS  1.3 CHEMICAL CONCEPTS  ACID-BASE REACTIONS  The addition or removal of hydrogen atoms is crucial in many biochemical processes  The autoionization of water The equilibrium expression for this process is K = [H+] [OH-] / [H2O], Kw = K [H2O] = [H+] [OH-] Kw is referred to as the ion-product constant for water. At 25C, Kw = 1.0  10-14 Kw is applicable to pure water and to any aqueous solution A solution in which [OH-] = [H+] is said to be neutral  1.3 CHEMICAL CONCEPTS  The pH scale  1.3 CHEMICAL CONCEPTS  How Important Is [H+] in Biology?  In a neutral solution [H+] = 1.0  10-7  Because H+ is present almost everywhere in cells, it is involved in many reactions.  [H+] variation can change the reaction rate. [H+] = 1.0  10-7 → 1.0  10-6 This change makes the reaction 10 times faster if it’s a 1st-order reaction for [H+] !!  1.3 CHEMICAL CONCEPTS  DNA DENATURATION AT LOW OR HIGH pH  DNA base pairing can be disrupted at low or high pH Fig 1.16 DNA denaturation by the addition of a base.  1.3 CHEMICAL CONCEPTS  Buffered solutions  Buffers are solutions of a weak conjugate acid- base pair.  They are particularly resistant to pH changes, even when strong acid or base is added.  Human blood pH 7.4, seawater pH 8.2.  Many important applications in the lab and in medicine.  1.3 CHEMICAL CONCEPTS  Buffered solutions HF ⇄ H+ + F-  1.3 CHEMICAL CONCEPTS  Buffered solutions (1 M HCl) (1 M HCl) Fig 1.17 Buffer action. Fig 1.18 Buffer protonation.  1.3 CHEMICAL CONCEPTS  The HH Equation In this condition, buffers have highest capacity.  1.4 THE GENOMIC REVOLUTION  The genomic revolution is transforming biochemistry and medicine  The discovery of DNA structure suggested: Hereditary information is stored as a sequence of bases along strands of DNA  This remarkable insight provided an entirely new way of thinking about biology  Now we know the basic biochemistry involved in the flow of genetic information from DNA to proteins  We also have full sequence information of many different organisms including human beings  Biochemistry have now become an information science.  1.4 THE GENOMIC REVOLUTION  Sequencing of the human genome  The human genome contains 3 billion base pairs  The sequencing of the human genome is truly a landmark in human history  This sequence contains a vast amount of information Some human diseases have been linked to particular variations in genomic sequence Sickle-cell anemia is caused by a single base change of an A to a T (Glu to Val)  The genome sequence is a source of deep insight into other aspects of human biology and culture Comparing the sequences of different individual persons and other organisms  1.4 THE GENOMIC REVOLUTION  What are the roles of genome sequences  The most fundamental role of DNA is to encode the sequences of proteins Proteins are linear polymers of amino acids  Genes, codons, and the genetic code  The human genome has only 23,000 protein-encoding genes; however the numbers of proteins are expanded by translational complexity and modification  The protein-encoding regions account for only about 3% of the human genome Some of it contains regulatory information; all cells contain the same genome, but different protein contents (hemoglobin and hormones)  1.4 THE GENOMIC REVOLUTION  Factors affecting individuality  Differences in genomic sequences Human beings has approximately 0.5% (one per 200 bases) variations in genomic sequences  Epigenetic factors Epigenetics is the study of heritable changes in gene expression or cellular DNA methylation and histone modification phenotype caused by mechanisms other than changes in the underlying DNA sequence  Environmental factors ―you are what you eat‖ – deficiency disorders (vitamins and trace elements), and rich foods (fats and carbohydrates) Exercise, and high stress levels