Aulani " Biokimia" Presentasi1 Chemical Foundations Aulanni’am Biochemistry Laboratory Chemistry Departement Brawijaya University

Aulani " Biokimia" Presentasi1 The Chemicals of Life

Aulani " Biokimia" Presentasi1 The Chemicals of Life Macromolecules

Aulani " Biokimia" Presentasi1 Covalent bonds Formed when two different atoms share electrons in the outer atomic orbitals Each atom can make a characteristic number of bonds (e.g., carbon is able to form 4 covalent bonds) Covalent bonds in biological systems are typically single (one shared electron pair) or double (two shared electron pairs) bonds

Aulani " Biokimia" Presentasi1 The making or breaking of covalent bonds involves large energy changes In comparison, thermal energy at 25ºC is < 1 kcal/mol

Aulani " Biokimia" Presentasi1 Covalent bonds have characteristic geometries

Aulani " Biokimia" Presentasi1 Covalent double bonds cause all atoms to lie in the same plane

Aulani " Biokimia" Presentasi1 Electrons are shared unequally in polar covalent bonds Atoms with higher electronegativity values have a greater attraction for electrons

Aulani " Biokimia" Presentasi1 water molecule has a net dipole moment caused by unequal sharing of electrons

Aulani " Biokimia" Presentasi1 Asymmetric carbon atoms are present in most biological molecules Carbon atoms that are bound to four different atoms or groups are said to be asymmetric The bonds formed by an asymmetric carbon can be arranged in two different mirror images (stereoisomers) of each other Stereoisomers are either right-handed or left-handed and typically have completely different biological activities Asymmetric carbons are key features of amino acids and carbohydrates

Aulani " Biokimia" Presentasi1 Stereoisomers of the amino acid alanine

Aulani " Biokimia" Presentasi1 Different monosaccharides have different arrangements around asymmetric carbons

Aulani " Biokimia" Presentasi1  and  glycosidic bonds link monosaccharides

Aulani " Biokimia" Presentasi1 Noncovalent bonds Several types: hydrogen bonds, ionic bonds, van der Waals interactions, hydrophobic bonds Noncovalent bonds require less energy to break than covalent bonds The energy required to break noncovalent bonds is only slightly greater than the average kinetic energy of molecules at room temperature Noncovalent bonds are required for maintaining the three-dimensional structure of many macromolecules and for stabilizing specific associations between macromolecules

Aulani " Biokimia" Presentasi1 Multiple weak bonds stabilize large molecule interactions

Aulani " Biokimia" Presentasi1 The hydrogen bond underlies water’s chemical and biological properties Molecules with polar bonds that form hydrogen bonds with water can dissolve in water and are termed hydrophilic

Aulani " Biokimia" Presentasi1 Hydrogen bonds within proteins

Aulani " Biokimia" Presentasi1 Ionic bonds Ionic bonds result from the attraction of a positively charged ion (cation) for a negatively charged ion (anion) The atoms that form the bond have very different electronegativity values and the electron is completely transferred to the more electronegative atom Ions in aqueous solutions are surrounded by water molecules, which interact via the end of the water dipole carrying the opposite charge of the ion

Aulani " Biokimia" Presentasi1 Ions in aqueous solutions are surrounded by water molecules

Aulani " Biokimia" Presentasi1 van der Waals interactions are caused by transient dipoles When any two atoms approach each other closely, a weak nonspecific attractive force (the van der Waals force) is created due to momentary random fluctuations that produce a transient electric dipole

Aulani " Biokimia" Presentasi1 Hydrophobic bonds cause nonpolar molecules to adhere to one another Nonpolar molecules (e.g., hydrocarbons) are insoluble in water and are termed hydrophobic Since these molecules cannot form hydrogen bonds with water, it is energetically favorable for such molecules to interact with other hydrophobic molecules This force that causes hydrophobic molecules to interact is termed a hydrophobic bond

Aulani " Biokimia" Presentasi1 Multiple noncovalent bonds can confer binding specificity

Aulani " Biokimia" Presentasi1 Phospholipids are amphipathic molecules

Aulani " Biokimia" Presentasi1 Phospholipids spontaneously assemble via multiple noncovalent interactions to form different structures in aqueous solutions

Aulani " Biokimia" Presentasi1 Chemical equilibrium The extent to which a reaction can proceed and the rate at which the reaction takes place determines which reactions occur in a cell Reactions in which the rates of the forward and backward reactions are equal, so that the concentrations of reactants and products stop changing, are said to be in chemical equilibrium At equilibrium, the ratio of products to reactants is a fixed value termed the equilibrium constant (K eq ) and is independent of reaction rate

Aulani " Biokimia" Presentasi1 Equilibrium constants reflect the extent of a chemical reaction K eq depends on the nature of the reactants and products, the temperature, and the pressure The K eq is always the same for a reaction, whether a catalyst is present or not K eq equals the ratio of the forward and reverse rate constants (K eq = k f /k r ) The concentrations of complexes can be estimated from equilibrium constants for binding reactions

Aulani " Biokimia" Presentasi1 Biological fluids have characteristic pH values All aqueous solutions, including those in and around cells, contain some concentration of H + and OH - ions, the dissociation products of water In pure water, [H + ] = [OH - ] = M The concentration of H + in a solution is expressed as pH pH = -log [H + ] So for pure water, pH = 7.0 On the pH scale, 7.0 is neutral, pH 7.0 is basic The cytosol of most cells has a pH of 7.2

Aulani " Biokimia" Presentasi1 The pH Scale

Aulani " Biokimia" Presentasi1 Hydrogen ions are released by acids and taken up by bases When acid is added to a solution, [H + ] increases and [OH - ] decreases When base is added to a solution, [H + ] decreases and [OH - ] increases The degree to which an acid releases H + or a base takes up H + depends on the pH

Aulani " Biokimia" Presentasi1 The Henderson-Hasselbalch equation relates the pH and K eq of an acid-base system The pK a of any acid is equal to the pH at which half the molecules are dissociated and half are neutral (undissociated) It is possible to calculate the degree of dissociation if both the pH and the pK a are known The Henderson-Hasselbalch equation pH = pK a + log — [A - ] [HA]

Aulani " Biokimia" Presentasi1 Cells have a reservoir of weak bases and weak acids, called buffers, which ensure that the cell’s pH remains relatively constant The titration curve for phosphoric acid (H 3 PO 4 ), a physiologically important buffer

Aulani " Biokimia" Presentasi1 Biochemical energetics Living systems use a variety of interconvertible energy forms Energy may be kinetic (the energy of movement) or potential (energy stored in chemical bonds or ion gradients)

Aulani " Biokimia" Presentasi1 The change in free energy determines the direction of a chemical reaction Living systems are usually held at constant temperature and pressure, so one may predict the direction of a chemical reaction by using a measure of potential energy termed free energy (G) The free-energy change (  G) of a reaction is given by  G = G products – G reactants If  G < 0, the forward reaction will tend to occur spontaneously If  G > 0, the reverse reaction will tend to occur If  G = 0, both reactions will occur at equal rates

Aulani " Biokimia" Presentasi1 The  G of a reaction depends on changes in enthalpy (bond energy) and entropy The  G of a reaction is determined by the change in bond energy (enthalpy, or H) between reactants and products and the change in the randomness (entropy, or S) of the system  G =  H - T  S In exothermic reactions (  H < 0), the products contain less bond energy than the reactants and the liberated energy is converted to heat In endothermic reactions (  H > 0), the products contain more bond energy than the reactants and heat is absorbed

Aulani " Biokimia" Presentasi1 Entropy Entropy is a measure of the degree of randomness or disorder of a system Entropy increases as the system becomes more disordered and decreases as it becomes more structured Many biological reactions lead to an increase in order and thus a decrease in entropy (  S < 0) Exothermic reactions (  H 0) occur spontaneously (  G < 0) Endothermic reactions (  H > 0) may occur spontaneously if  S increases enough so that T  S offsets the positive  H

Aulani " Biokimia" Presentasi1 Many cellular processes involve oxidation-reduction reactions Many chemical reactions result in the transfer of electrons without the formation of a new chemical bond The loss of electrons from an atom or molecule is termed oxidation and the gain of electrons is termed reduction If one atom or molecule is oxidized during a chemical reaction then another molecule must be reduced Many biological oxidation-reduction reactions involve the removal or addition of H atoms (protons plus electrons) rather than the transfer of isolated electrons

Aulani " Biokimia" Presentasi1 The oxidation of succinate to fumarate

Aulani " Biokimia" Presentasi1 An unfavorable chemical reaction can proceed if it is coupled to an energetically favorable reaction Many chemical reactions are energetically unfavorable (  G > 0) and will not proceed spontaneously Cells can carry out such a reaction by coupling it to a reaction that has a negative  G of larger magnitude Energetically unfavorable reactions in cells are often coupled to the hydrolysis of adenosine triphosphate (ATP), which has a  Gº = -7.3 kcal/mol The useful free energy in an ATP molecule is contained is phosphoanhydride bonds

Aulani " Biokimia" Presentasi1 The phosphoanhydride bonds of ATP

Aulani " Biokimia" Presentasi1 ATP is used to fuel many cell processes The ATP cycle

Aulani " Biokimia" Presentasi1 Activation energy and reaction rate Many chemical reactions that exhibit a negative  G°´ do not proceed unaided at a measurable rate Chemical reactions proceed through high energy transition states. The free energy of these intermediates is greater than either the reactants or products

Aulani " Biokimia" Presentasi1 Example changes in the conversion of a reactant to a product in the presence and absence of a catalyst Enzymes accelerate biochemical reactions by reducing transition-state free energy

Aulani " Biokimia" Presentasi1