Since the higher levels of protein structure depend on relatively weak bonds such
as hydrogen bonds, they are easily disrupted by increasing temperature or by changing
pH or ionic strength. Such changes may result in conversion of the protein to a non-
functional form, which is said to be denatured. These changes are often reversible.
For example, hair can be curled by wrapping it around a rod and heating. This
breaks hydrogen bonds, which re-form upon cooling, ‘‘freezing’’ the protein in the new
shape. However, there is tension in the hair fibers, and with time the hydrogen
bonds gradually rearrange into their former relationship, losing the curl. A ‘‘permanent’’
rearrangement can be made by using chem ical treatment, which breaks disulfide bonds
between cysteine residue s in hair proteins, then re-forms them in the curled shape. A
common example of irreversibly denaturing proteins by heat is the cooking of eggs.
Heat disrupts the globular albumin proteins, which do not return to their native state
upon cooling.
Enzymes are protein catalysts that increase biochemical reaction rates by factors
ranging from 10
6
to 10
12
over the uncatalyzed reactions. They often include non-
amino acid portions that may be organic or consist of metallic ions. These are called
cofactors.
Most enzymes are named with the suffix -ase. For example, lipase is an enzyme that
digests lipids. Another enzym e is lactase, which catalyzes the breakdown of milk sugar,
the disaccharide lactose, into monosaccharides glucose and galactose. Many adults, and
almost all non-Caucasian adults, lose their ability to produce lactase after early childhood.
However, some bacteria, including Escherichia coli, produce a different lactose-digesting
enzyme. Adults lacking lactase who eat milk products have abdominal disturbances when
the bacteria in the gut begin to produce gas using the lactose.
Enzymes are very specific; each catalyzes one or only a few different reactions, which
is sensitively controlled by its shape. It is remarkable that contrary to reactions in aqueous
media in the laboratory, enzyme-catalyzed reactions produce few side reac tions. Equally
remarkable is the fact that, with enzymes, a wide variety of reactions are promoted at mild
conditions of temperature, pressure, and pH.
Each enzyme has at least one active site, the location on the molecule that binds with
the substrate(s) (the reacta nts in the catalyzed reaction). The active site attracts the sub-
strate(s) and holds it, usually by physicochemical forces. Two major mechanisms by
which enzymes increase reaction rates are (1) by bringing the reactants close together,
and (2) by holding them in an orientation that favors the reaction (Figure 3.11). It is
also thought that enzymes can act by inducing strain in specific bonds of bound substrates,
making certain reactions favorable.
Since the shape of a molecule is so sensitive to its environment, the cell can turn reac-
tions on or off by changing conditions (e.g., pH) or by providing or withdrawing a cofac-
tor or inhibitory compound. Figure 3.12 shows how a cofactor could promote binding of a
single substrate with an enzyme. The cofactor binds first with the enzyme, changing the
shape of the active site. This allows the substrate to bind, forming the complex. As with
all proteins, denaturing stops the function of any enzyme.
Enzymes may also require coenzymes, which are molecules that function by accepting
by-products of the main reaction, such as hydrogen. Coenzymes differ from cofactors and
from enzymes themselves in that they are consumed by the reaction (although they may
be regenerated in other reactions). Examples include NAD and FAD, discussed below.
Some cofactors and coenzymes cannot be synthesized by mammals and must be included
in their diet, making them what we call vitamins.
56 THESUBSTANCESOFLIFE