Chapter 1 Introduction to Biomolecules

Biochemistry is concerned with the molecular workings of the body, and the first question we must ask is about the molecular composition of the normal human body. Table 1.1 lists the approximate composition of the proverbial 75-kg textbook adult. Next to water, proteins and triglycerides are most abundant. Triglyceride (aka fat) is the major storage form of metabolic energy and is found mainly in adipose tissue. Proteins are of more general importance. They are major elements of cell structures and are responsible for enzymatic catalysis and virtually all cellular functions. Carbohydrates, in the form of glucose and the storage polysaccharide glycogen, are substrates for energy metabolism, but they also are covalently linked components of glycoproteins and glycolipids. Soluble inorganic salts are present in all intracellular and extracellular fluids, and insoluble salts, most of them related to calcium phosphate, give strength and rigidity to human bones.

Table 1.1 Approximate Composition of a 75-Kg Adult

* In bones.

† In adipose tissue.

This chapter introduces the principles of molecular structure, the types of noncovalent interactions between biomolecules, and the structural features of the major classes of biomolecules.

Water is the solvent of life

Charles Darwin speculated that life originated in a warm little pond. Perhaps it really was a big warm ocean, but one thing is certain: We are appallingly watery creatures. Almost two thirds of the adult human body is water (see Table 1.1). The structure of water is simplicity itself, with two hydrogen atoms bonded to an oxygen atom at an angle of 105 degrees:

Water is a lopsided molecule, with its binding electron pairs displaced toward the oxygen atom. Thus the oxygen atom has a high electron density, whereas the hydrogen atoms are electron deficient. The oxygen atom has a partial negative charge (δ^–), and the hydrogen atoms have partial positive charges (δ⁺). Therefore the water molecule forms an electrical dipole:

Unlike charges attract each other. Therefore the hydrogen atoms of a water molecule are attracted by the oxygen atoms of other water molecules, forming hydrogen bonds:

These hydrogen bonds are weak. Only 29 kJ (7 kcal) per mole is needed to break a hydrogen bond in water, whereas 450 kJ (110 kcal) per mole* is required to break a covalent oxygen-hydrogen bond in the water molecule itself. Breaking the hydrogen bonds requires no more than heating the water to 100°C. The hydrogen bonds determine the physical properties of water, including its boiling point.

The water in the human body always contains inorganic cations (positively charged ions), such as sodium and potassium, and anions (negatively charged ions), such as chloride and phosphate. Table 1.2 lists the typical ionic compositions of intracellular (cytoplasmic) and extracellular (interstitial) fluid. Interestingly, the extracellular fluid has an ionic composition similar to seawater. We carry a warm little pond with us, to provide our cells with their ancestral environment.

Table 1.2 Typical Ionic Compositions of Extracellular (Interstitial) and Intracellular (Cytoplasmic) Fluids

	Concentration (mmol/L)
Ion	Extracellular Fluid	Cytoplasm
Na+	137	10
K+	4.7	141
Ca2+	2.4	10–4*
Mg2+	1.4	31
Cl–	113	4
HPO42–/H2PO4–	2	11
HCO3–	28†	10†
Organic acids, phosphate esters	1.8	100
pH	7.4	6.5–7.5

* Cytoplasmic concentration. Concentrations in mitochondria and endoplasmic reticulum are much higher.

† The lower HCO₃^– concentration in the intracellular space is caused by the lower intracellular pH, which affects the equilibrium:

Predictably, the cations are attracted to the oxygen atom of the water molecule, and the anions are attracted to the hydrogen atoms. The ion-dipole interactions thus formed are the forces that hold the components of soluble salts in solution, as in the case of sodium chloride (table salt):

The calcium phosphates in human bones are not soluble because the electrostatic interactions (“salt bonds”) between the anions and cations in the crystal structure are stronger than their ion-dipole interactions with water.

Water contains hydronium ions and hydroxyl ions

Water molecules dissociate reversibly into hydroxyl ions and hydronium ions:

   (1)

In pure water, only about one in 280 million molecules is in the H₃O⁺ or OH^– form:

   (2)

The brackets indicate molar concentrations (mol/L or M). One mole of a substance is its molecular weight in grams. Water has a molecular weight close to 18; therefore, 18 g of water is 1 mol. The hydronium ion concentration [H₃O⁺] usually is expressed as the proton concentration or the hydrogen ion concentration [H⁺], regardless of the fact that the proton is actually riding on the free electron pair of a water molecule.

In aqueous solutions, the product of proton (hydronium ion) concentration and hydroxyl ion concentration is a constant:

   (3)

The proton concentration [H⁺], otherwise measured in moles per liter, is more commonly expressed as the pH value, defined as the negative logarithm of the hydrogen ion concentration:

   (4)

With Equations (3) and (4), the H⁺ and OH^– concentrations can be predicted at any given pH value (Table 1.3).

Table 1.3 Relationship among pH, [H⁺], and [OH^–]

pH	[H+]*	[OH–]*
4	10−4	10–10
5	10−5	10–9
6	10–6	10–8
7	10–7	10–7
8	10–8	10–6
9	10–9	10–5
10	10–10	10–4

* [H⁺] and [OH^–] are measured in mol/L (M).

The pH value of an aqueous solution depends on the presence of acids and bases. According to the Brønsted definition, in aqueous solutions an acid is a substance that releases a proton, and a base is a substance that binds a proton. The prototypical acidic group is the carboxyl group, which is the distinguishing feature of the organic acids:

The protonation-deprotonation reaction is reversible; therefore, the carboxylate anion fits the definition of a Brønsted base. It is called the conjugate base of the acid.

Amino groups are the major basic groups in biomolecules. In this case, the amine is the base, and the ammonium salt is the conjugate acid:

Carboxyl groups, phosphate esters, and phosphodiesters are the most important acidic groups in biomolecules. They are mainly deprotonated and negatively charged at pH 7. Aliphatic (nonaromatic) amino groups, including the primary, secondary, and tertiary amines, are the most important basic groups. They are mainly protonated and positively charged at pH 7.

Ionizable groups are characterized by their pK values

The equilibrium of a protonation-deprotonation reaction is described by the dissociation constant (K_D). For the reaction

the dissociation constant K_D is defined as

   (5)

This can be rearranged to

   (6)

The molar concentrations in this equation are the concentrations observed at equilibrium. Because the hydrogen ion concentration [H⁺] is most conveniently expressed as the pH value, Equation (6) can be transformed into the negative logarithm:

   (7)

This equation is called the Henderson-Hasselbalch equation, and the pK value is defined as the negative logarithm of the dissociation constant. The pK value is a property of an ionizable group. If a molecule has more than one ionizable group, then it has more than one pK value.

In the Henderson-Hasselbalch equation, pK is a constant, whereas [R—COOH]/[R—COO⁻] changes with the pH. When the pH value equals the pK value, log[R—COOH]/[R—COO⁻] must equal zero. Therefore [R—COOH]/[R—COO⁻] must equal one: The pK value indicates the pH value at which the ionizable group is half-protonated. At pH values below their pK (i.e., high [H⁺] or high acidity), ionizable groups are mainly protonated. At pH values above their pK (i.e., low [H⁺] or high alkalinity), ionizable groups are mainly deprotonated (Table 1.4)

Table 1.4 Protonation State of a Carboxyl Group and an Amino Group at Different pH Values

Clinical Example 1.1: Acidosis

Blood and extracellular fluids have to provide a constant environment for our cells. Physiological levels of inorganic ions have to be maintained, and maintenance of a constant extracellular pH of 7.3 to 7.4 is required. Deviations from the normal pH by as little as 0.5 pH units can be fatal. An abnormally high pH of blood and interstitial fluid is called alkalosis, and an abnormally low pH is called acidosis. Many pathological processes can lead to alkalosis or acidosis. Acidosis can be caused by metabolic derangements leading to excessive formation of acidic products from nonacidic substrates. For example,

Some toxins are converted into acids in the human body, causing acidosis. For example,

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1. Digestive Enzymes
2. The Extracellular Matrix
3. Amino Acid Metabolism
4. Glycolysis, Tricarboxylic Acid Cycle, and Oxidative Phosphorylation

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