Lecture 1

1. Lecture 1 The Foundation of Biochemistry

2. What is Biochemistry？ • The study of biochemistry shows how the collections of inanimate molecules that constitute living organisms interact to maintain and perpetuate life governed solely by the physical and chemical laws that govern the nonliving universe.

3. Distinguishing features of living organisms • A high degree of chemical complexity and microscopic organization. • Systems for extracting, transforming, and using energy from the environment. • Defined functions for each of an organism’s components and regulated interactions among them. • Mechanisms for sensing and responding to alterations in their surroundings.

4. A capacity for precise self-replication and self-assembly. • A capacity to change over time by gradual evolution.

5. 1.1 Cellular Foundation

6. Cellular Foundation • All cells of the simplest and most complex organisms share certain fundamental properties, which can be seen at the biochemical level.

7. All cells have the followings: • bounded by a plasma membrane; • have a cytosol containing metabolites, coenzymes, inorganic ions, and enzymes; • have a set of genes contained within a nucleoid (bacteria and archaea) or nucleus (eukaryotes).

8. Limit of a cell • The lower limit - minimum number of each type of biomolecule required by the cell. • The upper limit - rate of diffusion of solute molecules in aqueous systems.

9. There are Three Distinct Domains of Life Inhabit soils, surface waters, and the tissues of other living or decaying organisms. Most inhabit extreme environments—salt lakes, hot springs, highly acidic bogs, and the ocean depths. Archaebacteriaare therefore more closely related to eukaryotes than to eubacteria.

10. Some common structural features of bacterial and archaeal cells

11. All organisms require a source of energy to perform cellular work. • Phototrophs obtain energy from sunlight. • Chemotrophsobtain energy from chemical fuels, oxidizing the fuel and passing electrons to good electron acceptors: inorganic compounds, organic compounds, or molecular oxygen.

12.  All organisms can be classified according to their source of energy.

13. Cytoskeletal proteins assemble into long filaments that give cells shape and rigidity and serve as rails along which cellular organelles move throughout the cell. • Supramolecular complexes held together by noncovalent interactions are part of a hierarchy of structures, some visible with the light microscope.

14. Structural hierarchy in the molecular organization of cells.

15. 1.2 Chemical Foundation

16. Chemical Foundation • Biochemistry aims to explain biological form and function in chemical terms. • Hydrogen, oxygen, nitrogen, and carbon are the most abundant elements in living organisms, in terms of percentage of total number of atoms. They make up more than 99% of the mass of most cells.

17.  Elements essential to animal life and health

18. Biomolecules are Compounds of Carbon with a Variety of Functional Groups • The chemistry of living organisms is organized around carbon, which accounts for more than half of the dry weight of cells. • Covalently linked carbon atoms in biomolecules can form linear chains, branched chains, and cyclic structures, affording great bonding versatility.

19. Versatility of carbon bonding Geometry of carbon bonding Av. bond length = 0.154 nm

20. Most biomolecules can be regarded as derivatives of hydrocarbons,with hydrogen atoms replaced by a variety of functional groups that confer specific chemical properties on the molecule, forming various families of organic compounds.

21. Strengths of bonds common in biomolecules

22.  Some common functional groups of biomolecules

23. The entire collection of small molecules in a given cell under a specific set of conditions has been called the metabolome. Several common functional groups in a single biomolecule of acetyl-Coenzyme A

24. Macromolecules are the Major Constituents of Cells • Macromolecules, polymers with molecular weights above ∼5,000 Da. • Shorter polymers are called oligomers. • Proteins, long polymers of amino acids, constitute the largest fraction (besides water) of a cell. 

25. Roles of proteins • Proteins have a number of different roles: • function as enzymes. • serve as structural elements, signal receptors, or transporters. • The sum of all the proteins functioning in a given cell is the cell’s proteome, and proteomics is the systematic characterization of this protein complement under a specific set of conditions.

26. Roles of nucleic acids • DNA and RNA, are polymers of nucleotides. They store and transmit genetic information, and some RNA molecules have structural and catalytic roles in supramolecular complexes. • The genome is the entire sequence of a cell’s DNA (or in the case of RNA viruses, its RNA), and genomics is the characterization of the structure, function, evolution, and mapping of genomes.

27. Polysaccharides • Function as • energy-rich fuel stores, • rigid structural components of cell walls (in plants and bacteria), • as extracellular recognition elements that bind to proteins on other cells. • Oligosaccharides attached to proteins or lipids at the cell surface serve as specific cellular signals. • A cell’s glycome is its entire complement of carbohydrate-containing molecules.

28. Lipids • Serve as structural components of membranes, energy-rich fuel stores, pigments, and intracellular signals. • The lipid-containing molecules in a cell constitute its lipidome.

29. Proteins and nucleic acids are often referred to as informational macromolecules. • Some oligosaccharides, as noted above, also serve as informational molecules.

30. Molecular Components of an E. coli Cell

31. Important features of biomolecules • Covalent bonds and functional groups. • Stereochemistry – the arrangement of the molecule’s constituent atoms in three-dimensional space. • Stereoisomers -molecules with the same chemical bonds and same chemical formula but different configuration (fixed spatial arrangement of atoms). • Interactions between biomolecules are invariably stereospecific.

32. Representations of molecules Structure formula Ball-and-stick model showing relative bond lengths and the bond angles. Space-filling model. Each atom is shown with its correct relative van der Waals radius

33. Configuration and stereoisomer • Configuration is conferred by the presence • double bonds, around which there is little or no freedom of rotation, or Maleic acid and fumaric acid are geometric isomers.

34. The energy of the absorbed light (about 250 kJ/mol) converts 11-cis-retinal to all-trans-retinal, triggering electrical changes in the retinal cell that lead to a nerve impulse

35. 2. Chiral centers, around which substituent groups are arranged in a specific orientation. A carbon atom with four different substituents is said to be asymmetric, and asymmetric carbons are called chiral centers.

36. A molecule with only one chiral carbon can have two stereoisomers; when two or more (n) chiral carbons are present, there can be 2n stereoisomers. • Stereoisomers that are mirror images of each other are called enantiomers. • Pairs of stereoisomers that are not mirror images of each other are called diastereomers.

37. stereoisomers of 2,3-disubstituted butane 

38. Properties of anantiomers • Nearly identical chemical reactivities but differ in a characteristic physical property: their interaction with plane-polarized light.  • In separate solutions, two enantiomers rotate the plane of plane-polarized light in opposite directions, but an equimolar solution of the two enantiomers (a racemic mixture) shows no optical rotation.

39. Naming of Biomolecules • The RS system, where each group attached to a chiral carbon is assigned a priority. The priorities of some common substituents are: OCH3> OH> NH2 > COOH > COH > CH2OH > CH3H • Another naming system for stereoisomers is the D and L system.

41. Molecularconformation, the spatial arrangement of substituent groups that, without breaking any bonds, are free to assume different positions in space because of the freedom of rotation about single bonds. Eclipsed conformation Conformation of ethane Staggered conformation

42. Interactions Between Biomolecules are Stereospecific • When biomolecules interact, the “fit” between them must be stereochemically correct. Complementary fit between a macromolecule (hexokinase) and a small molecule (glucose).

43. Chiral Molecules in Living Organisms • In living organisms, chiral molecules are usually present only in one of their chiral forms. Examples, L-amino acids in proteins and D-glucose. • This is because the enzymes that synthesize these molecules are themselves chiral. • Stereo specificity, the ability to distinguish between stereoisomers, is a property of enzymes and other proteins and a characteristic feature of biochemical interactions.

44. Stereoisomers have different effects in humans isolated from spearmint oil Isolated from caraway seed oil Antidepressant drug

45. 1.3 Physical Foundation

46. Physical Foundation • Living cells and organisms must perform work to stay alive and to reproduce themselves. • Energy input is needed for many cellular activities, including the storage and expression of information. • Cells possess highly efficient mechanisms for coupling the energy obtained from sunlight or chemical fuels to the many energy-requiring cellular processes.

47. Living Organisms Exist in a Dynamic Steady State • The characteristic composition of an organism changes little through time, the population of molecules within the organism exist in a dynamic static. • Small molecules, macromolecules, and supramolecular complexes are continuously synthesized and broken down in chemical reactions that involve a constant flux of mass and energy through the system.

48. What is a System? • A system is defined as all the constituent reactants and products, the solvent that contains them, and the immediate atmosphere—in short, everything within a defined region of space. • The system and its surroundings together constitute the universe. • Systems are classified into three types: isolated, closed and open systems.

49. An isolated system is one that exchanges neither matter nor energy with its surroundings. • A closed system is one that exchanges energy but not matter with its surroundings. • An open system exchanges both energy and matter with its surroundings.

50. Organisms Transform Energy and Matter from Their Surroundings • Living cells are open systems. • Organisms obtain energy from their surroundings by • taking up chemical fuels (e.g., glucose) from the environment and extract energy by oxidizing them; or • absorbing energy from sunlight.