Macromolecules Are the Major Constituents of CellsMany biological molecules are macromolecules, polymers of highmolecular weight assembled from relatively simple precursors.Proteins, nucleic acids, and polysaccharides are produced by thepolymerization of relatively small compounds with molecular weights of500 or less. The number of polymerized units can range from tens tomillions.Synthesis of macromolecules is a major energy-consuming activity ofcells.Macromolecules themselves may be further assembled intosupramolecular complexes, forming functional units such as ribosomes.
Configuration refers to the order that is determined bychemical bonds. The configuration of a polymercannot be altered unless chemical bonds are brokenand reformed.Conformation refers to order that arises from therotation of molecules about the single bonds. Thesetwo structures are studied below.
The covalent bonds and functional groups of a biomoleculeare, of course, central to its function, but so also is thearrangement of the molecule’s constituent atoms in three-dimensional space—its stereochemistry.A carbon-containing compound commonly exists asstereoisomers, molecules with the same chemical bonds butdifferent stereochemistry—that is, different configuration, thefixed spatial arrangement of atoms.Interactions between biomolecules are invariablystereospecific, requiring specific stereochemistry in theinteracting molecules.
A carbon atom with four different substituents is said to beasymmetric, and asymmetric carbons are called chiralcenters.A molecule with only one chiral carbon can have twostereoisomers; when two or more (n) chiral carbons arepresent, there can be 2n stereoisomers.Some stereoisomers are mirror images of each other; theyare called enantiomers. Pairs of stereoisomers that are notmirror images of each other are called diastereomers.
Given the importance of stereochemistry inreactions between biomolecules, biochemists mustname and represent the structure of each biomoleculeso that its stereochemistry is unambiguous.For compounds with more than one chiral center,the most useful system of nomenclature is the RSsystem.In this system, each group attached to a chiralcarbon is assigned a priority. The priorities of somecommon substituents are
For naming in the RS system, the chiral atom isviewed with the group of lowest priority pointing awayfrom the viewer. If the priority of the other three groups (1 to 3)decreases in clockwise order, the configuration is (R)(Latin rectus, “right”); if in counterclockwise order, theconfiguration is (S) (Latin sinister, “left”).In this way each chiral carbon is designated either(R) or (S), and the inclusion of these designations in thename of the compound provides an unambiguousdescription of the stereochemistry at each chiral center.
Plane-Polarized Light• Ordinary light: light vibrating in all planes perpendicular to its direction of propagation• Plane-polarized light: light vibrating only in parallel planes• Optically active: refers to a compound that rotates the plane of plane-polarized light
Plane-Polarized Light– plane-polarized light is the vector sum of left and right circularly polarized light– circularly polarized light reacts one way with an R chiral center, and the opposite way with its enantiomer– the result of interaction of plane-polarized light with a chiral compound is rotation of the plane of polarization
Plane-Polarized Light• Polarimeter: a device for measuring the extent of rotation of plane-polarized light
Specific Rotation• To have a basis for comparison, define specific rotation, [α]D for an optically active compound• [α]D = observed rotation/(pathlength x concentration) = α/(l x C) = degrees/(dm x g/mL)• Specific rotation is that observed for 1 g/mL in solution in cell with a 10 cm path using light from sodium metal vapor (589 nanometers)
Optical Activity– observed rotation: the number of degrees, α, through which a compound rotates the plane of polarized light– dextrorotatory (+): refers to a compound that rotates the plane of polarized light to the right– levorotatory (-): refers to a compound that rotates of the plane of polarized light to the left– specific rotation: observed rotation when a pure sample is placed in a tube 1.0 dm in length and concentration in g/mL (density); for a solution, concentration is expressed in g/ 100 mL
D-L System3 Carbon Sugar ?? Used particularly often for naming sugars and aminoacids:
The simplest aldose, glyceraldehyde, contains one chiral center(the middle carbon atom) and therefore has two different opticalisomers, or enantiomers.By convention, one of these two forms is designated the D isomer,the other the L isomer.As for other biomolecules with chiral centers, the absolutecconfigurations of sugars are known from x-ray crystallography.To represent three-dimensional sugar structures on paper, we oftenuse Fischer projection formulas.
The stereoisomers of monosaccharides of each carbon-chain lengthcan be divided into two groups that differ in the configuration about thechiral center most distant from the carbonyl carbon.Those in which the configuration at this reference carbon is the sameas that of D glyceraldehyde are designated D isomers, and those with thesame configuration as L glyceraldehyde are L isomers.When the hydroxyl group on the reference carbon is on the right in theprojection formula, the sugar is the D isomer; when on the left, it is the Lisomer.Of the 16 possible aldohexoses, eight are D forms and eight are L.Most of the hexoses of living organisms are D isomers.
• D,L designation refers to the configuration of the highest-numbered asymmetric center.• D,L only refers the stereocenter of interest back to D- and L-glyceraldehyde!• D,L do not specify the sign of rotation of plane- polarized light!• D-sugars predominate in nature.
The notation was extended to a-amino acids : Lenantiomers are those in which the NH2 group is onthe LHS of the Fischer projection in which thecarboxyl group appears at the top.Conversely, the D enantiomers are those in whichthe NH2 group is on the RHS. Thus (+)-alanine and(-)-serine are L-amino acids.
Distinct from configuration is molecular conformation, thespatial arrangement of substituent groups that, without breaking anybonds, are free to assume different positions in space because of thefreedom of rotation about single bonds.In the simple hydrocarbon ethane, for example, there is nearlycomplete freedom of rotation around the C-C bond.Many different, interconvertible conformations of ethane are possible,depending on the degree of rotation.Two conformations are of special interest: the staggered, which ismore stable than all others and thus predominates, and the eclipsed,which is least stable.
We cannot isolate either of these conformational forms,because they are freely interconvertible.However, when one or more of the hydrogen atoms on eachcarbon is replaced by a functional group that is either verylarge or electrically charged, freedom of rotation around the C-C bond is hindered.This limits the number of stable conformations of the ethanederivative.
Interactions between Biomolecules Are StereospecificBiological interactions between molecules are stereospecific: the“fit” in such interactions must be stereochemically correct.The three-dimensional structure of biomolecules large and smallthe combination of configuration and conformation—is of the utmostimportance in their biological interactions: reactant with enzyme,hormone with its receptor on a cell surface, antigenwith its specific antibody, for example.The study of biomolecular stereochemistry with precise physicalmethods is an important part of modern research on cell structure andbiochemical function.
In living organisms, chiral molecules are usually present inonly one of their chiral forms.For example, the amino acids in proteins occur only as theirL isomers; glucose occurs only as its D isomer.In contrast, when a compound with an asymmetric carbonatom is chemically synthesized in the laboratory, the reactionusually produces all possible chiral forms: a mixtureof the D and L forms, for example. Living cells produceonly one chiral form of biomolecules because the enzymesthat synthesize them are also chiral.
Stereospecificity, the ability to distinguish betweenstereoisomers, is a property of enzymes and other proteins anda characteristic feature of the molecular logic ofliving cells. If the binding site on a protein is complementary toone isomer of a chiral compound, it will not becomplementary to the other isomer, for the same reason that aleft glove does not fit a right hand.
Chirality in the Biological World– a schematic diagram of an enzyme surface capable of binding with (R)-glyceraldehyde but not with (S)-glyceraldehyde
Living Organisms Exist in a Dynamic Steady State, Never at Equilibrium with TheirSurroundingsThe molecules and ions contained within a living organismdiffer in kind and in concentration from those in theorganism’s surroundings.A Paramecium in a pond, a shark in the ocean, anerythrocyte in the human bloodstream, an apple tree in anorchard—all are different in composition from theirsurroundings and, Once they have reached maturity, all (to a firstapproximation) maintain a constant composition in the face ofconstantly changing surroundings.
Organisms Transform Energy and Matter from Their SurroundingsFor chemical reactions occurring in solution, we can define a system as all thereactants and products present, the solvent that contains them, and the immediateatmosphere— in short, everything within a defined region of space.The system and its surroundings together constitute the universe.If the system exchanges neither matter nor energy with its surroundings, it is said tobe isolated.If the system exchanges energy but not matter with its surroundings, it is a closedsystem; if it exchanges both energy and matter with its surroundings, it is an opensystem.
living organism is an open system; it exchangesboth matter and energy with its surroundings.Living organisms derive energy from theirsurroundings in two ways: (1) they take up chemicalfuels (such as glucose) from the environment andextract energy by oxidizing them; or (2) they absorbenergy from sunlight
The first law of thermodynamics, developed from physics and chemistry but fully valid forbiological systems as well, describes the principle of the conservation of energy:in any physical or chemical change, thetotal amount of energy in the universeremains constant, although the form of theenergy may change.Cells are consummate transducers of energy, capable of interconverting chemical,electromagnetic, mechanical, and osmotic energy with great efficiency
The Flow of Electrons Provides Energy for OrganismsNearly all living organisms derive their energy,directly or indirectly, from the radiant energy ofsunlight, which arises from thermonuclear fusionreactions carried out in the sun.Photosynthetic cells absorb light energy and use itto drive electrons from water to carbon dioxide,forming energy-rich products such as glucose(C6H12O6), starch, and sucrose and releasing O2 intothe atmosphere:
Creating and Maintaining Order Requires Work andEnergyDNA, RNA, and proteins are informationalmacromolecules.In addition to using chemical energy to form the covalentbonds between the subunits in these polymers, the cell mustinvest energy to order the subunits in their correct sequence.It is extremely improbable that amino acids in a mixturewould spontaneously condense into a single type of protein,with a unique sequence.
This would represent increased order in a population ofmolecules; but according to the second law ofthermodynamics, the tendency in nature is toward ever-greater disorder in the universe:the total entropy of the universe is continually increasing.To bring about the synthesis of macromolecules fromtheir monomeric units, free energy must be supplied tothe system (in this case, the cell).
The randomness or disorder of the components of achemical system is expressed as entropy, S.Any change in randomness of the system isexpressed as entropy change, S, which by conventionhas a positive value when randomness increases.J. Willard Gibbs, who developed the theory ofenergy changes during chemical reactions, showed thatthe free energy content, G, of any closed system canbe defined in terms of three quantities:enthalpy, H, reflecting the number and kinds ofbonds;entropy, S; and theabsolute temperature, T (in degrees Kelvin).
Gibbs free energy, G, expresses the amount of energycapable of doing work during a reaction at constanttemperature and pressure. When a reaction proceedswith the release of free energy (that is, when thesystem changes so as to possess less free energy), thefree-energy change, G, has a negative value and thereaction is said to be exergonic. In endergonicreactions, the system gains free energy and G ispositive.
Free Energy & Spontaneity What is the name of this molecule?
Free Energy & Spontaneity Source of EnergySpontaneous Reaction Non-spontaneous Reaction
Energy Coupling via ATP (1/2) Energy for Anabolism
The definition of free energy GWhen a chemical reaction occurs atconstant temperature, the free-energychange, G, is determined by the enthalpychange, H, reflecting the kinds and numbersof chemical bonds and noncovalentinteractions broken and formed, and theentropy change, S, describing the change inthe system’s randomness:
Enthalpy, H, is the heat content of the reacting system. It reflectsthe number and kinds of chemical bonds in thereactants and products.When a chemical reaction releases heat, it is said tobe exothermic; the heat content of the products is lessthan that of the reactants and H has, by convention, anegative value. Reacting systems that take up heat from theirsurroundings are endothermic and have positivevalues of H.
Entropy, S,is a quantitative expression for the randomness or disorderin a system.When the products of a reaction are less complex and moredisordered than the reactants, the reaction is said to proceedwith a gain in entropy.
A process tends to occur spontaneously only if G isnegative.Yet cell function depends largely on molecules, such asproteins and nucleic acids, for which the free energy offormation is positive: the molecules are less stable and morehighly ordered than a mixture of their monomeric components.To carry out these thermodynamically unfavorable, energyrequiring (endergonic) reactions, cells couple them to otherreactions that liberate free energy (exergonic reactions), sothat the overall process is exergonic: the sum of the freeenergy changes is negative.
The usual source of free energy in coupled biologicalreactions is the energy released by hydrolysis ofphosphoanhydride bonds such as those in adenosinetriphosphate.
[C] [D] ∆ G = ∆ Gº + RT lnAt equilibrium [A] [B]∆G = 0. [C] [D]Keq, the ratio [C][D]/[A] 0 = ∆ Gº + RT ln [A] [B][B] at equilibrium, is theequilibrium constant. [C] [D] ∆ Gº = - RTln [A] [B]An equilibrium constant(Keq) greater than one [C] [D] defining Keq =indicates a spontaneous [A] [B]reaction (negative ∆G°). ∆ Gº = - RT ln Keq
When a reacting system is not at equilibrium,the tendency to move toward equilibriumrepresents a driving force, the magnitude of whichcan be expressed as the free-energy change for thereaction, G.Under standard conditions (298 K 25 C), whenreactants and products are initially present at 1 Mconcentrations or, for gases, at partial pressures of101.3 kilopascals (kPa), or 1 atm, the force drivingthe system toward equilibrium is defined as thestandard free-energy change, G0.
By this definition, the standard state forreactions that involve hydrogen ions is [H] = 1 M,or pH 0.Most biochemical reactions, however, occur inwell-buffered aqueous solutions near pH 7; boththe pH and the concentration of water (55.5 M) areessentially constant.
∆Go = − RT ln Keq Variation of equilibrium constant with ∆Go‘ (25 oC) Keq ∆ º G Starting with 1 M reactants & kJ/mol products, the reaction: 4 10 - 23 proceeds forward (spontaneous) 2 10 - 11 proceeds forward (spontaneous) 010 = 1 0 is at equilibrium -2 10 + 11 reverses to form “reactants” -4 10 + 23 reverses to form “reactants”
Free energy of oxidation of single-carbon compoundsIn aerobic organisms, the ultimate electron acceptor in theoxidation of carbon is O2, and the oxidation product is CO2The more reduced a carbon is, the more energy from its oxidation
One caution about the interpretation of G:thermodynamic constants such as this showwhere the final equilibrium for a reaction liesbut tell us nothing about how fast thatequilibrium will be achieved.The rates of reactions are governed by theparameters of kinetics,
Enzyme Catalytic Cycle I nput o f Act iva En tion erg y
Mechanisms of CatalysisMetal Ion or =Organic Molecule = Organic Cofactor Polypeptide
Problem 1St Reaction of GlycolysisUse the table to :2. Find standard transformed free energy change of this reaction3. Couple the reaction with ATP hydrolysis4. Write the overall Reaction5. Calculate the standard transformed free energy change of overall reaction
First Exam Next MondayLet’s try to avoid the scholastic equivalent of this!