Chapter 2 – Orientation for the Bio-Curious  45

E. This proton motive force is then coupled to the rotation of the FoF1–​ATP synthase in the

membrane to generate ATP. For the TCA cycle, each molecule of glucose is ultimately broken

down into a theoretical maximum of 38 molecules of ATP based on standard relative chem­

ical stoichiometry values of the electron-​carrier proteins and how many electrons can be

transferred at each step, though in practice the maximum number is less in a living cell and

more likely to be 30–​32 ATP molecules per glucose molecule.

The pmf is an example of a chemiosmotic proton gradient (for a historical insight, see

Mitchell, 1961). It constitutes a capacitance electrostatic potential energy. This potential

energy can be siphoned off by allowing the controlled translocation of protons down the

gradient through highly specific proton channels in the membrane. In a mechanism that is

still not fully understood, these translocating protons can push around a paddle-​wheel-​type

structure in a molecular machine called the “FoF1ATP synthase.” The FoF1ATP synthase

is a ubiquitous molecular machine in cells composed of several different protein subunits,

found inside bacteria, chloroplasts in plants, and most importantly to us humans in mito­

chondria. The machine itself consists of two coupled rotary motors (see Okuno et al., 2011).

It consists of an inner water-​soluble F1 motor exposed to the cellular cytoplasm with a rotor

shaft protein called γ surrounded by six stator units composed of alternating α and β proteins

(Figure 2.5c). There is also an outer hydrophobic Fo motor linked to the rotor shaft. Under

more normal conditions, the Fo motor couples the chemiosmotic energy stored in the proton

gradient across the cell membrane lipid bilayer to the rotation of the F1 motor that results in

ATP being synthesized from ADP and inorganic phosphate (but note that under conditions

of oxygen starvation the motors can hydrolyze ATP and rotate in the opposite direction,

causing the protons to be pumped up the proton gradient).

KEY POINT 2.14

ATP is the universal cellular fuel, made by transforming the chemical and electrostatic

potential energy across specific dielectric phospholipid bilayers into mechanical rota­

tion of the FoF1 ATP synthase molecular machine (really two counter-​rotating motors

of Fo and F1), which is coupled to chemically synthesizing ATP from ADP and inor­

ganic phosphate.

2.4.4  NATURAL SELECTION, NEO-​DARWINISM, AND EVOLUTION

Neo-​Darwinism, which evokes classical natural selection concepts of Darwinism in the con­

text of modern genetics theory, has been described by some life scientists as the central para­

digm of biology. The essence of the paradigm is that living organisms experience a variety

of selective pressures, and that the organisms best adapted to overcome these pressures will

survive to propagate their genetic code to subsequent generations. By a “selective pressure,”

biologists mean some sort of local environmental parameter that affects the stochastic

chances of an organism surviving, for example, the abundance or scarcity of food, tempera­

ture, pressure, the presence of oxygen and water, and the presence of toxic chemicals. In any

population of organisms, there is a distribution of many different biological characteristics,

which impart different abilities to thrive in the milieu of these various selective pressures,

meaning that some will survive for longer than others and thus have a greater chance of

propagating their genetic code to subsequent generations either through asexual cell division

processes or through sexual reproduction.

This in essence is the nuts and bolts of natural selection theory, but the devil is very much

more in the detail! Neo-​Darwinism accounts for the distribution in biological characteristics

of organisms through genetics, namely, in the underlying variation of the DNA nucleotide

sequence of genes. Although the cellular machinery that causes the genetic code in DNA to

be replicated includes error-​checking mechanisms, there is still a small probability of, for

example, a base pairing mismatch error (see Question 2.7), somewhere between 1 in 10⁵ (for

certain viruses) and 10⁹ (for many bacteria and eukaryotic cells) per replicated nucleotide