1、08/21/08,Biochemistry: Introduction,1,Introduction to Biochemistry,Andy Howard Biochemistry, Fall 2008 IIT,08/21/08,Biochemistry: Introduction,p. 2 of 62,What is biochemistry?,By the end of this course you should be able to construct your own definition; but for now: Biochemistry is the study of che
2、mical reactions in living tissue.,08/21/08,Biochemistry: Introduction,p. 3 of 62,Plans,What is biochemistry? Cells Cell components Organic and biochemistry Concepts from organic chemistry to remember Small molecules and macromolecules,Classes of small molecules Classes of macromolecules Water Cataly
3、sis Energetics Regulation Molecular biology Evolution,08/21/08,Biochemistry: Introduction,p. 4 of 62,What will we study?,Biochemistry is the study of chemical reactions in living tissue, both within cells and in intercellular media. As such, it concerns itself with a variety of specific topics:,08/2
4、1/08,Biochemistry: Introduction,p. 5 of 62,Topics in biochemistry,What reactions occur; The equilibrium energetics and kinetics of those reactions; How the reactions are controlled, at the chemical and cellular or organellar levels; How the reactions are organized to enable biological function withi
5、n the cell and in tissues and organisms.,08/21/08,Biochemistry: Introduction,p. 6 of 62,Organic and biological chemistry,Most molecules in living things (other than H2O, O2, and CO2) contain C-C or C-H bonds, so biochemistry depends heavily on organic chemistry But the range of organic reactions tha
6、t occur in biological systems is fairly limited compared to the full range of organic reactions:,08/21/08,Biochemistry: Introduction,p. 7 of 62,Why we use only a subset of organic chemistry in biochemistry,Biochemical reactions are almost always aqueous. They occur within a narrow temperature and pr
7、essure range. They occur within narrowly buffered pH ranges. Many of the complex reaction mechanisms discovered and exploited by organic chemists since the 1860s have no counterparts in the biochemical universe.,Frederich Whler,08/21/08,Biochemistry: Introduction,p. 8 of 62,Cells,Most biochemical re
8、actions (but not all!) take place within semi-independent biological entities known as cells Cells in general contain replicative and protein-synthetic machinery in order to reproduce and survive They often exchange nutrients and information with other cells,08/21/08,Biochemistry: Introduction,p. 9
9、of 62,Cell components,Cells are separated from their environments via a selectively porous membrane Individual components (often called organelles) within the cell may also have membranes separating them from the bulk cytosol and from one another,08/21/08,Biochemistry: Introduction,p. 10 of 62,Eukar
10、yotes and prokaryotes,The lowest-level distinction among organisms is on the basis of whether their cells have defined nuclei or not Cells with nuclei are eukaryotic Cells without nuclei are prokaryotic Eubacteria and archaea are prokaryotic Other organisms (including some unicellular ones!) are euk
11、aryotic,08/21/08,Biochemistry: Introduction,p. 11 of 62,Eukaryotic organelles I,Nucleus: contains genetic information; site for replication and transcription Endoplasmic reticulum: site for protein synthesis and protein processing Ribosome: protein-synthetic machine Golgi apparatus: site for packagi
12、ng proteins for secretion and delivery,08/21/08,Biochemistry: Introduction,p. 12 of 62,Eukaryotic organelles II,Mitochondrion: site for most energy-producing reactions Lysosome: digests materials during endocytosis and cellular degradation Peroxisome: site for oxidation of some nutrients and detoxif
13、ication of the H2O2 created thereby Cytoskeleton: network of filaments that define the shape and mobility of a cell,08/21/08,Biochemistry: Introduction,p. 13 of 62,Eukaryotic organelles III,Chloroplast: site for most photosynthetic reactions Vacuoles: sacs for water or other nutrients Cell wall: bac
14、terial or plant component outside cell membrane that provides rigidity and protection against osmotic shock,08/21/08,Biochemistry: Introduction,p. 14 of 62,Concepts from organic chemistry,There are some elements of organic chemistry that you should have clear in your minds. All of these are concepts
15、 with significance outside of biochemistry, but they do play important roles in biochemistry. If any of these concepts is less than thoroughly familiar, please review it:,08/21/08,Biochemistry: Introduction,p. 15 of 62,Organic concepts I,Covalent bond: A strong attractive interaction between neighbo
16、ring atoms in which a pair of electrons is roughly equally shared between the two atoms. Covalent bonds may be single bonds, in which one pair of electrons is shared; double bonds, which involve two pairs of electrons; or triple bonds, which involve three pairs (see above). Single bonds do not restr
17、ict the rotation of other substituents around the bond; double and triple bonds do.,Image courtesy Michigan State U.,08/21/08,Biochemistry: Introduction,p. 16 of 62,Organic concepts II,Ionic bond: a strong attractive interaction between atoms in which one atom or group is positively charged, and ano
18、ther is negatively charged.,08/21/08,Biochemistry: Introduction,p. 17 of 62,Organic concepts III,Hydrogen bond: A weak attractive interaction between neighboring atoms in which a hydrogen atom carrying a slight, partial positive charge shares that positive charge with a neighboring electronegative a
19、tom. The non-hydrogen atom to which the hydrogen is covalently bonded is called the hydrogen-bond donor; the neighboring atom that takes on a bit of the charge is called the hydrogen-bond acceptor,Cartoon courtesy CUNY Brooklyn,08/21/08,Biochemistry: Introduction,p. 18 of 62,Organic concepts IV,Van
20、der Waals interaction: A weak attractive interaction between nonpolar atoms, arising from transient induced dipoles in the two atoms.,Image courtesy Columbia U. Biology Dept.,08/21/08,Biochemistry: Introduction,p. 19 of 62,Organic Concepts V,Chirality: The property of a molecule under which it canno
21、t be superimposed upon its mirror image.,Image courtesy DRECAM, France,08/21/08,Biochemistry: Introduction,p. 20 of 62,Organic Concepts VI,Tautomerization: The interconversion of two covalently different forms of a molecule via a unimolecular reaction that proceeds with a low activation energy. The
22、two forms of the molecule are known as tautomers: because of the low activation barrier between the two forms, we will typically find both species present.,acetone,propen-2-ol,08/21/08,Biochemistry: Introduction,p. 21 of 62,Organic Concepts VII,Nucleophilic substitution: a reaction in which an elect
23、ron-rich (nucleophilic) molecule attacks an electron-poor (electrophilic) molecule and replaces group or atom within the attacked species. The displaced group is known as a leaving group. This is one of several types of substitution reactions, and it occurs constantly in biological systems.,08/21/08
24、,Biochemistry: Introduction,p. 22 of 62,Organic Concepts VIII,Polymerization: creation of large molecules by sequential addition of simple building blocks often by dehydration, i.e., the elimination of water from two species to form a larger one: R1-O-H + HO-R2-X-H R1-X-R2-OH + H2O The product here
25、can then react with HO-R3-X-H to form R1-X-R2-X-R3-OH with elimination of another water molecule, and so on.,08/21/08,Biochemistry: Introduction,p. 23 of 62,Organic Concepts IX,Equilibrium: in the context of a chemical reaction, the state in which the concentrations of reactants and products are no
26、longer changing with time because the rate of reaction in one direction is equal to the rate in the opposite direction. Kinetics: the study of the rates at which reactions proceed. Conventionally, we use the term thermodynamics to describe our understanding of the energetics of equilibrium systems,0
27、8/21/08,Biochemistry: Introduction,p. 24 of 62,Organic Concepts X,Catalysis: the lowering of the energetic barrier between substrates and products in a reaction by the participation of a substance that ultimately is unchanged by the reaction It is crucial to recognize that catalysts (chemical agents
28、 that perform catalysis) do not change the equilibrium position of the reactions in which they participate: they only change the rates (the kinetics) of the reactions they catalyze. Zwitterion: a compound containing both a positive and a negative charge,08/21/08,Biochemistry: Introduction,p. 25 of 6
29、2,Classes of small molecules,Small molecules other than water make up a small percentage of a cells mass, but small molecules have significant roles in the cell, both on their own and as building blocks of macromolecules. The classes of small molecules that play significant roles in biology are list
30、ed below. In this list, “soluble“ means “water-soluble“.,08/21/08,Biochemistry: Introduction,p. 26 of 62,iClicker quiz (for attendance),How many midterms will we have? (a) 1 (b) 2 (c ) 3 (d) 4 (e) I dont care.,08/21/08,Biochemistry: Introduction,p. 27 of 62,Biological small molecules I,Water: Hydrog
31、en hydroxide. In liquid form in biological systems. See below. Lipids: Hydrophobic molecules, containing either alkyl chains or fused-ring structures. A biological lipid usually contains at least one highly hydrophobic moeity.,08/21/08,Biochemistry: Introduction,p. 28 of 62,Biological small molecule
32、s II,Carbohydrates: Polyhydroxylated compounds for which the building blocks are highly soluble. The typical molecular formula for the monomeric forms of these compounds is (CH2O)n, where 3 n 9, but usually n = 5 or 6.,08/21/08,Biochemistry: Introduction,p. 29 of 62,Biological small molecules III,Am
33、ino acids: Compounds containing an amine (NH3+) group and a carboxyl (COO-) group. The most important biological amino acids are a-amino acids, in which the amine group and the carboxyl group are separated by one carbon, and that intervening carbon has a hydrogen attached to it. Thus the general for
34、mula for an a-amino acid is H3N+ - CHR - COO-,08/21/08,Biochemistry: Introduction,p. 30 of 62,Biological small molecules IV,Nucleic acids: Soluble compounds that include a nitrogen-containing ring system. The ring systems are derived either from purine or pyrimidine. The most important biological nu
35、cleic acids are those in which the ring system is covalently attached to a five-carbon sugar, ribose, usually with a phosphate group attached to the same ribose ring.,08/21/08,Biochemistry: Introduction,p. 31 of 62,Small molecules V,Inorganic ions: Ionic species containing no carbon but containing o
36、ne or more atoms and at least one net charge. Ions of biological significance include Cl-, Na+, K+, Mg+2, Mn+2, I-, Ca+2, PO4-3, SO4-2, NO3-, NO2-, and NH4+. Phosphate (PO4-3) is often found in partially protonated forms HPO4-2 and H2PO4- Ammonium ions occasionally appear as neutral ammonia (NH3), p
37、articularly at higher pH values,08/21/08,Biochemistry: Introduction,p. 32 of 62,Biological Small Molecules VI,Cofactors: This is a catchall category for organic small molecules that serve in some functional role in biological organisms. Many are vitamins or are derived from vitamins; a vitamin is de
38、fined as an organic molecule that is necessary for metabolism but cannot be synthesized by the organism. Thus the same compound may be a vitamin for one organism and not for another. Ascorbate (vitamin C) is a vitamin for humans and guinea pigs but not for most other mammals. Cofactors often end up
39、as prosthetic groups, covalently or noncovalently attached to proteins and involved in those proteins functions.,08/21/08,Biochemistry: Introduction,p. 33 of 62,Biological macromolecules,Most big biological molecules are polymers, i.e. molecules made up of large numbers of relatively simple building
40、 blocks. Cobalamin is the biggest nonpolymeric biomolecule I can think of (MW 1356 Da),Structure courtesy Wikimedia,08/21/08,Biochemistry: Introduction,p. 34 of 62,Categories of biological polymers,Proteins Nucleic acids Polysaccharides Lipids (sort of): 2-3 chains of aliphatics attached to a polar
41、head group, often built on glycerol Aliphatic chains are usually 11-23 Cs,08/21/08,Biochemistry: Introduction,p. 35 of 62,Polymers and oligomers,These are distinguished only by the number of building-blocks contained within the multimer Oligomers: typically 50 building blocks Polymers 50 building bl
42、ocks.,08/21/08,Biochemistry: Introduction,p. 36 of 62,Categories of biopolymers,08/21/08,Biochemistry: Introduction,p. 37 of 62,Water: a complex substance,Oxygen atom is covalently bonded to 2 hydrogens Single bond character of these bonds means the H-O-H bond angle is close to 109.5 = acos(-1/3): a
43、ctually more like 104.5 This contrasts with O=C=O (angle=180) or urea (NH2)2-C=O) (angles=120) Two lone pairs available per oxygen: these are available as H-bond acceptors,08/21/08,Biochemistry: Introduction,p. 38 of 62,Water is polar,Charge is somewhat unequally shared Small positive charge on Hs (
44、d+); small negative charge on O (2d-) (Why?) A water molecule will orient itself to align partial negative charge on one molecule close to partial positive charges on another. Hydrogen bonds are involved in this.,08/21/08,Biochemistry: Introduction,p. 39 of 62,Liquid water is mobile,The hydrogen-bon
45、d networks created among water molecules change constantly on a sub-picosecond time scale At any moment the H-bonds look like those in crystalline ice Solutes disrupt the H-bond networks,08/21/08,Biochemistry: Introduction,p. 40 of 62,Water in reactions,Water is a medium within which reactions occur
46、; But it also participates in reactions Enzymes often function by making water oxygen atoms better nucleophiles or water Hs better electrophiles Therefore water is a direct participant in reactions that wouldnt work in a nonenzymatic lab setting!,08/21/08,Biochemistry: Introduction,p. 41 of 62,Water
47、s physical properties,High heat capacity: stabilizes temperature in living things High surface tension Nearly incompressible (density almost independent of pressure) Density max at 3.98C,08/21/08,Biochemistry: Introduction,p. 42 of 62,Catalysis,Catalysis is the lowering of the activation energy barr
48、ier between reactants and products How? Physical surface on which reactants can be exposed to one another Providing moieties that can temporarily participate in the reaction and be restored to their original state at the end,08/21/08,Biochemistry: Introduction,p. 43 of 62,Biological catalysts,1890s:
49、 Fischer realized that there had to be catalysts in biological systems 1920s: Sumner said they were proteins It took another 10 years for the whole community to accept that Its now known that RNA can be catalytic too: Can catalyze modifications in itself Catalyzes the key step in protein synthesis i
50、n the ribosome,08/21/08,Biochemistry: Introduction,p. 44 of 62,Energy in biological systems,We distinguish between thermodynamics and kinetics: Thermodynamics characterizes the energy associated with equilibrium conditions in reactions Kinetics describes the rate at which a reaction moves toward equilibrium,
