Erdinç Devrim, MD

Professor of Medical Biochemistry

devrim@ankara.edu.tr
 Water (H2O) is the main chemical component of living
organisms.
 It is a reactant or product in various metabolic reactions.
 It has a slight tendency to dissociate into hydroxide ions
(OH-) and protons (H+).

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 The concentration of protons of aqueous solutions is
reported using the logarithmic pH scale.
 Bicarbonate, phosphate and other buffers function to
maintain the pH of blood between 7.35 and 7.45.
 Acidosis (blood pH <7.35) vs. alkalosis (blood pH >7.45).

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 8O16: 1s2 2s2 2px2 2py1 2pz1

 1H1: 1s1

..
 H O
.. H

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 The water (H2O) molecule has tetrahedral geometry.
 The strongly electronegative oxygen atom in a water molecule attracts electrons
away from the hydrogen nuclei, leaving them with a partial positive charge,
meantime its two unshared electron pairs constitute a region of local negative
charge.
 A molecule with electrical charge distributed asymmetrically about its structure is
referred to as a dipole.
 Its strong dipole and high dielectric constant facilitate water to dissolve large
quantities of charged compounds like salts.

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From Essentials of Medical Biochemistry: With Clinical Cases,
Second Edition. Copyright © 2015 Elsevier Inc. All rights
reserved. 6
 A partially unshielded hydrogen nucleus covalently bound to an
electron-withdrawing oxygen or nitrogen atom can interact with an
unshared electron pair on another oxygen or nitrogen atom to form a
hydrogen bond.
 Hydrogen bonding greatly influences the physical properties of water
and clarifies its relatively high viscosity, surface tension, and boiling
point.
 Water molecules self-associate via hydrogen bonds.
 Hydrogen bonding enables water to dissolve many organic
biomolecules that contain functional groups which can participate in
hydrogen bonding.

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From Essentials of Medical Biochemistry: With Clinical Cases,
Second Edition. Copyright © 2015 Elsevier Inc. All rights
reserved. 8
 The covalent bond is the strongest force that holds molecules together.
 Noncovalent forces, while of lesser magnitude, make significant
contributions to the structure, stability, and functional competence of
macromolecules in living cells.
 Hydrogen bonds
 Electrostatic (ionic) interactions
 Hydrophobic interactions
 van der Waals forces

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 Metabolic reactions often involve the attack by lone pairs of electrons
residing on electron-rich molecules termed nucleophiles upon electron-
poor atoms called electrophiles.
 Water, whose two lone pairs of sp3 electrons bear a partial negative charge,
is an excellent nucleophile.
 Nucleophilic attack by water typically results in the cleavage of the amide
(peptide), glycoside, or ester bonds that hold biopolymers together
(hydrolysis).
 When monomer units are joined together to form biopolymers, such as
proteins or glycogen, water is a product.

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 The ability of water to ionize, while slight, is of central
importance for life.
 Since water can act both as an acid and as a base, its
ionization may be represented as an intermolecular proton
transfer that forms a hydronium ion (H3O+; represented as
H+) and a hydroxide ion (OH−):

 Simply, water dissociates as:

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 For dissociation of water,

 Kw termed the ion product for water. The relationship between Kw and K is as
shown below:

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 The ion product Kw is numerically equal to the product of the molar concentrations
of H+ and OH−:

 For pure water, at 25oC (room temperature) Kw equals to 10-14 (mol/L)2, therefore
[H+] in pure water is 10-7 mol/L.

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 For pure water at 25°C,

Therefore, pH of the pure water is 7.

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 Low pH values correspond to high concentrations of H+ and high pH values
correspond to low concentrations of H+.
 Acids are proton donors and bases are proton acceptors.
 Strong acids (e.g., HCl, H2SO4) completely dissociate into anions and protons even
in strongly acidic solutions (low pH).
 Weak acids dissociate only partially in acidic solutions.
 Similarly, strong bases (e.g., KOH, NaOH), but not weak bases such as Ca(OH)2,
are also completely dissociated even at high pH.

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 Many biochemicals possess functional groups that are weak acids or bases.
 Knowledge of the dissociation of weak acids and bases thus is basic to
understanding the influence of intracellular pH on structure and biologic
activity.
 We term the protonated species (HA or R-NH3+) the acid and the
unprotonated species (A- or R-NH2) its conjugate base.
 Similarly, we may refer to a base (A- or R-NH2) and its conjugate acid (HA
or R-NH3+).

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 The relative strengths of weak acids and bases are expressed
in terms of their dissociation constants.
 Shown below is the expression for the dissociation constant
(Ka) for a representative weak acid, R-COOH.

 Since the numeric values of Ka for weak acids are negative

exponential numbers, we express Ka as pKa, where

 The stronger the acid, the lower is its pKa value.

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 From the above equations that relate Ka to [H+] and to the
concentrations of undissociated acid and its conjugate base,
when

 then,

 Thus, when the protonated and its conjugate base species are
present at equal concentrations, the prevailing hydrogen ion
concentration [H+] is numerically equal to the dissociation
constant, Ka.

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 Since −log Ka is defined as pKa, and −log [H+] defines pH, the equation
may be rewritten as

 Finally, the pKa of an acid group is the pH at which the protonated

and unprotonated species are present at equal concentrations.

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 A weak acid, HA, ionizes as follows:

 The equilibrium constant for this dissociation is

 Cross-multiplication gives

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 Divide both sides by [A−]:

 Take the log of both sides:

 Multiply through by −1:

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 Substitute pH and pKa for −log [H+] and −log Ka, respectively; then

 Inversion of the last term removes the minus sign and gives the
Henderson-Hasselbalch equation:

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 Solutions of weak acids or bases and their conjugates exhibit buffering, the ability
to resist a change in pH following addition of strong acid or base.
 In other words, buffers resist a change in pH when protons are produced or
consumed.
 Biologic maintenance of a constant pH involves buffering by bicarbonate,
orthophosphate, proteins, and hemoglobin (in red blood cells), which accept or
release protons to resist a change in pH.
 A solution of a weak acid and its conjugate base buffers most effectively in the pH
range pKa ± 1.0 pH unit.

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From Essentials of Medical Biochemistry: With Clinical Cases,
Second Edition. Copyright © 2015 Elsevier Inc. All rights
reserved. 24
 Harper’s Illustrated Biochemistry, 30th Edition. Rodwell VW, Bender DA,
Botham KM, Kennely PJ, Weil PA. Lange, 2015. (Chapter 2)
 Marks’ Basic Medical Biochemistry A Clinical Approach, Second Edition.
Smith C, Marks AD, Lieberman M. Lippincott Williams & Wilkins, 2005.
(Chapter 4)
 Essentials of Medical Biochemistry with Clinical Cases, Second Edition.
Bhagavan NV, Ha C-E, Academic Press, 2015. (Chapter 2)
 Lehninger Principles of Biochemistry, Sixth Edition. Nelson DL, Cox MM.
W.H. Freeman and Company 2013. (Chapter 2)

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