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2.3  Chemicals that Make Cells Work

lysine and arginine); and the so-​called disulfide bonds (–​S–​S–​) that can occur between two

nearby cysteine amino acids, resulting in a covalent bond between them via two sulfur (–​

S) atoms. Cysteines are often found in the core of proteins stabilizing the structure. Living

cells often contain reducing agents in aqueous solution, which are chemicals that can reduce

(bind hydrogen to or remove oxygen from) chemical groups, including a disulfide bond

that would be broken by being reduced back into two cysteine residues (this effect can be

replicated in the test tube by adding artificial reducing agents such as dithiothreitol [DTT]).

However, the hydrophobic core of proteins is often inaccessible to such chemicals. Additional

nonsecondary structure hydrogen bonding effects also occur between sections of the same

amino acids, which are separated by more than 10 amino acids.

These molecular forces all result in a 3D fine-​tuning of the structure to form complex

features that, importantly, define the shape and extent of a protein’s structure that is actually

exposed to external water-​solvent molecules, that is, its surface. This is an important feature

since it is the interface at which physical interactions with other biological molecules can

occur. This 3D structure formed is known as the protein tertiary structure (Figure 2.5c). At

this level, some biologists will also refer to a protein being fibrous (i.e., a bit like a rod), or

globular (i.e., a bit like a sphere), but in general most proteins adopt real 3D conformations

that are somewhere between these two extremes.

Different protein tertiary structures often bind together at their surface interfaces to form

larger multimolecular complexes as part of their biological role. These either can be sep­

arate tertiary structures all formed from the same identical amino acid sequence (i.e., in

effect identical subunit copies of each other) or can be formed from different amino acid

sequences. There are several examples of both types in all domains of life, illustrating an

important feature in regard to biological complexity. It is in general not the case that one

simple protein from a single amino acid sequence takes part in a biological process, but more

typically that several such polypeptides may interact together to facilitate a specific process

in the cell. Good examples of this are the modular architectures of molecular tracks upon

which molecular motors will translocate (e.g., the actin subunits forming F-​actin filaments

over which myosin molecular motors translocate in muscle) and also the protein hemoglobin

found in the red blood cells that consists of four polypeptide chains with two different pri­

mary structures, resulting in two α-​chains and two β-​chains. This level of multimolecular

binding of tertiary structures is called the “quaternary structure.”

Proteins in general have a net electrical charge under physiological conditions, which is

dependent on the pH of the surrounding solution. The pH at which the net charge of the pro­

tein is zero is known as its isoelectric point. Similarly, each separate amino acid residue has

its own isoelectric point.

Proteins account for 20% of a cell by mass and are critically important. Two broad types

of proteins stand out as being far more important biologically than the rest. The first belongs

to a class referred to as enzymes. An enzyme is essentially a biological catalyst. Any cata­

lyst functions to lower the effective free energy barrier (or activation barrier) of a chemical

reaction and in doing so can dramatically increase the rate at which that reaction proceeds.

That is the simple description, but this hides the highly complex detail of how this is actu­

ally achieved in practice, which is often through a very complicated series of intermediate

reactions, resulting in the case of biological catalysts from the underlying molecular het­

erogeneity of enzymes, and may also involve quantum tunneling effects (see Chapter 9).

Enzymes, like all catalysts, are not consumed per se as a result of their activities and so

can function efficiently at very low cellular concentrations. However, without the action

of enzymes, most chemical reactions in a living cell would not occur spontaneously to any

degree of efficiency over the time scale of a cell’s lifetime. Therefore, enzymes are essential

to life. (Note that although by far the majority of biological catalysts are proteins, another

class of catalytic RNA called “ribozymes” does exist.) Enzymes in general are named broadly

after the biological process they primarily catalyze, with the addition of “ase” on the end of

the word.

The second key class of proteins is known as molecular machines. The key physical char­

acteristic of any general machine is that of transforming energy from one form into some type

of mechanical work, which logically must come about by changing the force vector (either in