in this introductory chapter of part I we examine elements that are indispensable for the

unhindered reading of the remainder of the book, in particular, the chapter contains elementary
concepts of chemistry, a presentation of the classes of biological substances, and a brief
description of the cell and its components.

1.1 Chemical Elements

The matter that surrounds us, and the matter that we are made of, is composed of chemical
elements such as hydrogen, oxygen, and carbon. The smallest unit of each element that maintains
its properties is the atom. Every atom consists of the nucleus and the surrounding electrons. The
nucleus contains protons, which carry a positive electric charge, and neutrons, which are neutral.
Electrons carry a negative charge of equal absolute value to that of protons. Thus, an atom-in
which the number of electrons equals the number of protons-is electrically neutral.

Electrons move arround a nucleus not in definite orbits, but within atomic orbitals. Each atomic
orbital is described by a complex mathematical equation from which chemists can calculate the
probability of finding an electron in a specific position relative to the nucleus. Schematically, the
position of electrons is depicted by electron clouds, which are denser where there is a high
probabillity of finding electrons than where there is low probability of finding electrons.

Ninety-two elements exist in nature. In living organisms, however, we find just about 29. Six of
them occupy the overwhelming majority of the mass of biological substances. These elements
are hydrogen (symbolized as H), carbon (C), nitrogen IN), oxygen (O), phosphorus (P), and
sulfur (S). Table 1.1 presents some features of these elements.

Atomic Number

The atonic number of an element in the number of protons in its nucleus, For the elements in
table 1.1, it ranges from 1 to 16. In contrast to the number of neutrons in the nucleus, the atomic
number is characteristic of and unique to every element. This means that two atoms of the same
element have to have the same number of protons, but their number of neutrons may differ. If
this is the case, the atoms are called lsotapes. For example, while the vast majority of carbon
atoms in nature have six protons and six neutrons (these atoans are symbolized as 12C), a small
percentage (1.1%] prossess seven neutrons (these atoms are therefore symbolized as 17C.

Atomic Mass

Atomic mass (also known as atomic weight) of an element is the mass of one of its atoms. The
unit of atomic mass is the Dalton. It is symbolized as Da and defined as one-twelfth of the mass
of a 12C atom. One dalton is an inconceivably small mass, just 1,66 10-24.

Rounded up to the nearest integer, the atomic mass coincides with the sum of protons and
neutrons in the nucleus of the predominant isotope of each element, for the relatively light
elements. Thus, the atomic mass of hydrogen is approximately 1 Da, and its main isotope has
only one proton in its nucleus, while the atomic mass of phosphorus is almost 31 Da, and its
predominant isotope has 15 protons and 16 neutrons.

Their mass having been described, it is worth completing the picture of atoms with reference to
their size. The size, too, is infinitesimal. As a unit of measure we use the angstrom (A), which
equals 10-10 m. The atomic diameter of the six most abundant elements in living organisms
ranges from 0,7 to 2,2 A.

Before we proceed, and since we have already considered some units, it is useful to remember
that in order to express multiples and submultiples of units. we frequently add prefixes to their
symbols; some prefixes are presented in table 1.2.

1.2 Chemical Bonds

Atoms form chemical bonds with atoms of the same element or different elements. A chemical
bond requires at least two clectrons, which in must cases are contributed mutualy by the atoms
participating in the bond. According to the current scientific view, the movement of these
electrons is constrained. Thus, whereas before bond formation it is described by isolated atomic
orbitals, after bond formation it obeys the equations of new orbitals, termed molecular orbitals.

The bond formed when two atoms share electrons is called covalent. If each atom contributes
one electron, a single bond is formed, symbolized as a thin line between the atoms. Two atoms
may be linked by a double or even a triple bond. These are formed by two or three electron pairs
and are symbolized as a double or triple line, respectively.

The number of bonds that an atom form is dictated by the distribution of electrons in its atomic
orbitals. Knowing this number is essential for the correct construction of molecular formulas, as
we will see later. The numbers of covalent bonds formed by the six most abundant elements in
living organisms are shown in the last column of table 1.1. Thus, the atoms of the elements that
compose biological molecules can be joined covalently to one, two, three, or four atoms (Note
that although table 1.1 shows that p can form five bonds, two of them are directed toward one
atom as a double bond. Therefore, P bonds with four atoms. See figure 2,3 for examples.)

1.3 Molecules

Atoms are joined by covalent bonds to form molecules. For example, two hydrogen atoms
connected by a single bond form a hydrogen molecule. If the molecules of substance are
composed of atoms belonnging to deifferent elements, then the substance is called a compound.
Water, consisting of two hydrogens linked to an onsygen, is the must abundant compound in our
bodies

Molecular Formula
What a compound is made of is depicted by its molecular formula, which contains thc symbols
of the elements present in the compound along with the numbers of their atoms as subscripts if
they exceed 1. Thus, the molecular formula of water H2O. From a molecular formula we can
calculate the molecular mass that is, the sum of the atomic masses of the elements constituting
the molecule (naturally, first we have to multiply the atomic mass of every element by the
number of atoms in the compound). Like atomic mass, molecular mass is measured in daltons, lf,
alternatively, we express it in grams, we get one mole of the compound, which is symbolized as
mol. Thus, the molecular mass of water is 18 Da(1-2+6), and 1 mol of it is 18 gr.

Constitutional Formula

In addition to the kind and number of atoms in the molecule of a compound, chemists are
interested in the way the atoms are connected. Such information is provided by constitutional
formulas, which we can construct by knowing the number of bonds that each atom can form.
This is where the last column of table 1.1 comes into play. The rule is that each atom has to be
surrounded by as many bonds as that column dictates. Verify the rule by examining the
compound of figure 1.1a, which is the amino acid alenine. (Amino acids are dealt with in chapter
3.)

Constitutional formulas can be detailed (showing all bonds among atoms) or abbreviated. For
example, we can simplify the formula of alanine by substituting -COOH for the group of atoms
at the right-hand side of the molecule, known in organic chemistry as the carboxyl group (figure
1.1 b). Likewise, we can substitute -NH2, for the group of atoms at the left-hand side, known as
the amino group and -CH, for the group of atoms at the top, known as the methyl group. Two
compounds may have the same molecular formula but different constitutional formulas because
of different configurations of the same atoms. Such compounds are called isomeric.

1.4 lons

Molecules are electrically neutral, as the are composed of neutral atoms. However, most
compounds in biological fluids are in the form of ions; that is, they carry electric charges. This
happens because some atoms are more stable if they have more or fewer electrons than the
number tallying with their protons.

A molecule in a biological fluid can be easily converted to an ion through the exchange of one or
more hydrogen ions H+ with its surroundings. H+ is nothing more than a proton; thus, it is
extremely mobile. Where does H+ come from? Water itself dissociates to a small degree to H+
and hydroxyl ion (OH-), thus supplying material for the formation of ions.

Because of their structure, some groups, such as the carboxyl group, have the tendency to release
a proton, thus acquiring a negative charge (-COO-). In contrast, other groups, like the amino
group, have the tendency to attract a proton, thus acquiring a positive charge (-NH3+).. An
example of an ion (in fact, an ion bearing two charges) is presented in figure 1.1c. Note that an
ion such as that of alanine may be neutral as a whole If the positive charges equal the negative
ones Positively charged ions are termed cations; negatively charged ions are anions; and ions
bearing both kinds of charge are zwitterions (zwitter is German for “both at the same time".

Most ions have their electrons in pairs, but some do not. These are called radicals (or free
radicals, a redundant term), and we usually denote their unpaired electron by a dot in addition to
the charge symbol. For exemple, the superoxide radical, produced by the addition of an electron
to an oxygen molecule, is symbolized as O 2- . Other radicals, such as the hydroxyl rodical (HO-,
not to be confused with the hydroxyl ion), carry no charge and are not ions. As we will see in
section 9.11, radicals are produced naturally in the body and increase during exercise.

1.5 Polarity Influences Miscibility

Although the positive and negative charges are equal in the neutral molecules of any compound.
they may not be evenly distributed. The reason is that the nuclei of some atoms (notably N and
O) attract bonding electrons more strongly than the nuclei of other atoms do. Thus, atoms of the
former kind acquire a partial negative charge (symbolized as & and pronounced delta minus),
whereas atoms of the latter kind acquire a partial positive charge (6+), In such molecules, we can
discern a negative and a positive electric pole, and we call the compound polar (figure 1.2). On
the other hand. if charges are evenly distributed within the molecules of a compound, we call it
nonpolar.

The polarity of a substance (that is, whether and to what degree it is polar) affects one of its
important physical properties: the miscibility (that is, the ability to mix) with other substances.
Here's how

 Polar substances tend to mix with polar substances.

 Nonpolar substances tend to mix with nonpolar substances.

 A polar and a nonpolar substance do not mix readily.

These interactions verify the saying “Birds of feather flock together.”

1.6 Solution

When the mixing of two or more substances results in a homogeneous mixture, that is a mixture
having the same composition all over its mass, we call it a solution. In a solution, we usually
distinguish the solvent, that is, the substance present in the highest proportion, from the solute(s),
that is, the dissolved substance(s). We define the concentration of a solute as the amount of it that
is contained in a certain amount of solution or solvent. A common unit of concentration is mole
per liter of solution (mol/ L, or mol L-1, or M). This is referred to as molar concentration.
The term concentration is often used loosely for mixtures that do not qualify as solutions (they
are not homogeneous), such as many biological fluids. The concentrations of substances
dissolved in biological fluids are relatively low. The highest ones are in the order of 10 -2 mol L-1,
whereas the lowest ones are as low as 10-12 mol L+.

The solvent in biological systems as water. It is a polar compound (figure 1.3) and, as such, it
mixes readily with other polar compounds, which are thus called hydrophilic (meaning "water
loving” in Greek). Sugar is an example of a hydrophilic compound. In contrast, nonpolar
compounds do not mix readily with water and are thus called hydrophobic (“water fearing"). Oils
are examples of hydrophobic compounds. Their droplets are repelled by water and tend to
aggregate and form drops. Naturally, nonpolar compounds dissolve in nonpolar solvents. A
common nonpolar solvent is the spot remover used to take away oily stains from clothes.

1.7 Chemical Reactions and Equilibrium

Often the compounds present in a mixture do not stay inert but interact to form new compounds.
These interactions are called chemical reactions. A chemical reaction differs from a physical
process in that in the latter, no new compounds are produced. For example, the dissolution of
sugar in a cup of coffee is a physical process, since no new compounds are formed (sugar
molecules just go from being embedded in a crystal to being surrounded by water molecules). In
contrast, the burning of a piece of wood involves several chemical reactions (one of which is the
conversion of cellulose to carbon dioxide and water)

Is life the outcome of chemical reactious or physical processes? Both! Thousands of reactions
take place within organisms to enable them to produce energy and build their components. On
the other hand, thousands of physical processes, such as the dissolution or diffusion of an ion
into a biological fluid or the binding together of two molecules, let biological molecules interact
and convey messages. In fact, most biological processes involve both chemical and physical
interactions in the aqueous environment of biological fluids.

The substances participating in a chemical reaction are termed reactants, while the substances
produced are the products. To represent a reaction chemists write its equation, which includes
two sides usually divided by a one-way arrow or two opposite arrows. The following is an
example of a chemical equation.

Equation 1.1 represented the hydrolysis, that is, the breakdown by water, of urea-a simple
biological compound-to ammonia and carbon dioxide. The bidirectional arrows signify that the
reaction is reversible, and this is the rule for chemical reactions. Which way reaction will go
depends on energy factors that we will explore in section 2.1. If a reaction is left to proceed far
enough, it reaches a state in which no change in the concentration of any of the participating
substances is detected. This is called the equilibrium and is characterized by the equilibrium
constant, K(), which is the ratio of the molar concentrations of the products to the molar
concentrations oí the reactants. For equation 1 1.
If a substance participates in a reaction by a number of molecules that is different from 1 (as is
the case with ammonia in our example), then we raise its concentration to this number in the K eq
expression-thus, (NH3)2 instead of (NH3).

The value of Keq depends on the nature of the reactants and products, the temperature, the
pressure, and, occasionally, the presence of other substances in the reaction medium. Certain
reactions go almost completely (quantitatively, as we say) in one direction under certain
circumstances and are characterized as irreversible. In these cases, we are allowed to use a one-
way arrow.

Chemical reactions are governed by the principle of mass conservation, which dictates that atoms
neither form nor vanish (they are only rearranged). Because of this, the two sides of chemical
equation must have the same kind and number of atoms. To ensure the principle of mass
conservation, one may have to add numbers in front of some reactants or products. In the case of
equation 1.1, we had to insert the number 2 in front of ammonia.

Reactions involving ions are additionalily governed by the principle of charge conservation,
which requires that the algebraic sum of charges be equal on the two sides the equation. To
achieve this one may have to add one or more H+ to one of the two sides.

A balanced chemical equation is one that complies with the two principles just laid out.
Compared to an unbalanced equation, it has the advantage of offering quantitative as well as
qualitative information on the reaction it represents. In other words, it shows not only which
compounds participate in the reaction and what the products are, but also what the proportions of
molecules and moles are. Equation 1.1 informs us that one mole(cule) of urea and one
mole(cule) of water produce two mole(cule)s of ammonia and one mole(cule) of carbon dioxide.
All chemical equations in this books are balanced.

1.8 PH

The ease with which protons are detached from chemical compounds or added to them (as we
saw happening during the formation of ions) endows them with an important role in chemical
processes. Because (H+) is usually very low (for example, 10-7 mol L-1 in pure water), chemists
have established a convenient index of it, pH. pH is defined as the negative decimal logarithm of
the molar concentration of protons.

pH = -log10 (H+), or (H+) = 10 -pH

pH is a dimensionless quantity (it has no units). The pH of pure water is 7 because of the
dissociation of a minuscule fraction of its molecules to H + and OH-. When the pH of a solution is
7, the solution is neutral (figure 1.4). If an acid (defined here as a proton donor) is added, then
the pH increases and the pH drops (because of the negative sign on the right-hand side in
equation 1.3).
The solution then becomes acidic (examples of acidic solutions are lemon juice and vinegar) If, n
the other hand, a base (defined here as a proton acceptor) is added to a neutral solution, then the
(H+) decreases and the pH rises. The solution then becomes alkaline or basic (examples of
alkaline solutions are whitewash and soapy water). The pH of most biological fluids is nearly
neutral and is called physiological. As we will see in subsequents chapters, this pH can change
with exercise. The pH of the blood is 7.3 to 7.4.

1.9 Acid-Base Interconversions

If a compound in aqueous solution can exchange protons with its environment, its form is not
fixed but depends on the pH of the solution. Such a compound binds protons when the pH
decreases (because the [H+] increases) and loses protons when the pH increases (because the [H+]
decreases). Let's explore these transitions by using alanine as an example.

The predominant form of alanine in a neutral solution is the one shown in figure 1.1c. If an acid
(such as HCl) is added, its H+ will tend to associate with the negatively charged carboxyl group
of alanine and neutralize it.

or A + H+ = AH+ if we substitute A for alanine. We refer to the Keq, of the reverse reaction (that is,
the dissociation of AH+ to A and H+) as the dissociation constant, K.

We further define pK as -log K. The pK of equation 1.4 as 2.3. We can intcoduce pK and pH into
equation 1.5 by taking the logarithms of its two sides.

Therefore

Or

which is known as the Henderson-Hasselbalch equation. This equation establishes a relationship

between pH, pK and the concentration ratio of a base to its conjugate acid, which permits the
calculation of any of the three when the other two are known.

An interesting relationship arises when pH = pK. According to the Henderson Hasselbalch

equation,

Therefore

Or

Thus equal concentrations of a conjugate acid and base are present when pH= pK. In the case of
alanine, half of it carries an ionized and half of it carries an un-ionized carboxyl group at pH 2.3.
It also follows from the Henderson-Hasselbelch equation that the conjugate acid predominates
when pH < pK, whereas the conjugate base predominates when pH > pK. This is why the
carboxyl group of alanine is deprotonated in a neutral solution. Lets’s consider now what
happens when we add a base (such as NaOH) to a neutral alanine solution. By analogy to the
previous discussion, the OH- of the base will tend to remove H+ from the positively charged
amino group and neutralize it.

Equation 1.9 is characterized by a different pK equaling 9 9. Thus at pH 9.9, half of alanine will
carry an ionized amino group and half of it will carry an un-ionize amino group, while the amino
group will be protonated in a neutral solution.

Troughout this book, constitutional formulas of ionizable compounds will depict the
predominant form at physiological pH. Additionally, the names of acids will refilect the fact that
they are ionized at physiological pH. Thus, we will refer to phosphate rather than phosphoric
acid, aspartate rather than aspartic acid, palmitate rather than palmitic acid, lactate rather than
lactic acid, and so on.

Because changes in the pH of a solution affect the form of the ionizable solutes, which in turn
affects the interactions and reactions among them, cells and multicellular organisms have devised
ways to maintain the pH of their fluids constant. For example, as mentioned in the previous
section, the pH of the blood remains between 7 3 and 7.4. To protect the pH of their fluids
against fluctuations caused by the production of acids ar bases, living organisms have
compounds of high buffering capacity, defined as the amount of strong acid or base needed to
change the pH by one unit. These compounds usually come in pairs of conjugate acid and base,
which are interconverted upon absorbing H+or OH- (as in equations 1.4 and 1.9); thus preventing
H+or OH- from changing the pH.

A buffer system consisting of a conjugate acid base pair in solution is not efficient at every pH
value. Rather, its buftering capacity is maximal at pH = pK, where the cencentrations of the
conjugate acid and base are equal. The buffering capacity gradually decreases as one draws away
from the pK. We will consider three important systems, based on proteins, bicarbonate, and
phosphate, later in this book (sections 3.5, 3.12, and 8.4, respectively).

1.10 Classes of Biological Substances

Studying biochemistry is facilitated by dividing biological substances into classes. More versatile
and more interesting are the organic compounds, those based on carbon. There are four major
classes of biologicsł organic compounds: proteins, nucleic acids, carbohydrates, and lipids.

These classes differ greatly in structure and function. Most of their molecules are big and are
characterized as macromolecules. How big are these macromolecules? They can contain millions
of atoms. To study them would be despairingly difficult did they not consist of smaller units
identical or similar to cach other. These building blocks are easier to study; they are called
monomers (meaning “single parts” in Greek), whereas the macromolecules resulting from
joining monomers together are called polymers (“multiple parts”)
Apart from organic substances, living organisms contain inorganic substances. Water alone
composes over half of their mass. In addition, a multitude of inorganic ions are dissolved in
biological fluids or bound to organic compounds. Most abundant among these ions are sodium
(Na+), potassium (K+), chloride (Cl-), calcium (Ca2+), magnesium (Mg2+), hydrogen carbonate or
bicarbonate (HCO3-), and hydrogen phosphate (HPO42-).

1.11 Cell Structure

The cell is the building block of living organisms. Primitive organisms such as bacteria are
unicellular, whereas organisms that appeared later in the course of the evolution of life are
multicellular. The human body consists of approximately I014 (100 trillion!) cells.

The size of cells varies. A bacterial cell is about 1 µm in diameter, whereas the cells of
multicellular organisms are usually 10 to 100 times larger. An average human cell is about 25 µm
in diameter.

All cells of multicellular organisms are not the same. Cells in the skin are different from those in
muscle, which are different from those in the brain. Almost 200 cell types have been identified
in the human body.

Despite their great diversity-both from species to species and within the same organism-cells
have many features in common (figure 1.5). To begin with their boundaries, all are enclosed in a
membrane called the plasma membrane. The plasma membrane is only 60 to 100 Å thick and
consists of lipids and proteins, to which carbohydrates may be attached.

The interior of a cell is called the cytoplasm. Its main component is water, which surrounds a
multitude of molecules, ions and molecular complexes. The cytoplasm is fairly uniform in the
simplest of cells, the prokaryotic cells. Prokaryotes were the first form of life to appear on Earth
some 3.5 billion years ago and comprise two main groups, bacteria and archaea. On the other
hand, multicellular organisms (but also many unicellular organisms such as fungi), which
appeared on Earth during the past two billion years, consist of cells that are more complex. These
are called eukaryotic cells.

Eukaryotic cels have internal compartments, or organelies, bounded by membranes similar to the
plasma membrane. The largest, densest, and most conspicuous intracellular organelle is the
nucleus. The nucleus contains the main genetic material of the cell, which is a nucleic acid
known by the initials DNA (short for deoxyribonucleic acid).

The nucleus is surrounded by an extensive network of tubules and flattened sacs, the
endoplasmic reticulums. The endoplasmic reticulum is the site of synthesis, storage, and
transport of substances to other parts of the cell or outside the cell. It ends in a similar, though
more distinct, system of flattened sacs, stacked one on top of each other and called the Golgi
apparatus, or Golgi complex. This is where proteins to be secreted outside the cell are packaged
and, sometimes, processed.
The cytoplasm of eukaryotic cells is filled with oval organelles named mitochondria (singular:
mitochondrion). Mitochondria are the power plants of the cell: They are the main sites where
nutrients are burned by oxygen and energy is produced for cellular functions. Other organelles
include lysosomes and peroxisomes, specialized sites where cellular components are broken
down. What is left of the cytoplasm outside all intracellular organelles is the cytosol.