Classic Biochemical Reactions and Pathways
ATP Hydrolysis

ATP is considered the energy "currency" of the cell. But how much is that currency worth? How much energy is in an ATP? The hydrolysis of one phosphate bond to form ADP and phosphate

ATP + H2O ⇌ ADP + Pi

has a ΔrG'° of about -26 kJ / mol. That is, if you hydrolyze 1 mol of ATP to ADP in standard conditions, 26 kJ of energy that is usable for work is released. Conversely, it takes 26 kJ of work to form 1 mol of ATP from ADP in standard conditions.

Keep in mind that ΔrG'° is defined in standard conditions (1 molar concentrations) while biological concentrations are much closer to 1 millimolar (1 mM). Try using eQuilibrator to figure out the ΔrG' of ATP hydrolysis in these conditions (answer: ~44 kJ / mol).

The Oxidation of Glucose

The oxidation of glucose is a major source of chemical energy for most organisms. Indeed, most of the energy harvested from glucose oxidation is stored as ATP. If we take a look at the full oxidation of glucose to carbon dioxide and water

Glucose + 6 O2 ⇌ 6 CO2 + 6 H2O

we find that ΔrG'° is about -2930 kJ / mol. At more biological 1 mM concentrations, ΔrG' ≈ -2910 kJ / mol. According to our calculation from above, that's enough energy to make 66 ATP. But most organisms generate only about 30 ATP by burning glucose.

Biochemistry textbooks often write this reaction as generating 36 ATP

Glucose + 6 O2 + 36 ADP + 36 Pi ⇌ 6 CO2 + 42 H2O + 36 ATP

giving a ΔrG' of around -1350 kJ / mol (when all concentrations are 1 mM). In other words, there's more free energy! Which begs the question: why not make more ATP? If you're interested in learning why, consider looking up "chemical motive force" for reversible reactions.

Glycolysis and Fermentation

The reason that glucose oxidation produces so much energy is that molecular oxygen has a strong "preference" to accept electrons (high reduction potential). This preference of electrons to flow to oxygen is so powerful that it can be used to drive the formation of several ATP. This process is called oxidative phosphorylation. In anaerobic conditions, however, oxygen is not available (by definition) and it's impossible to drive oxidative phosphorylation.

The anaerobic breakdown of glucose for energy production is called fermentation. Several approaches to fermenting glucose occur in nature, but here we'll discuss only one: fermentation of glucose to lactate. The fermentation of glucose begins in the same way that the oxidation of glucose does: with the breakdown of glucose to two pyruvate molecules, also known as glycolysis:

Glucose ⇌ 2 Pyruvate

If you inspect this reaction in eQuilibrator, you'll notice that it is not "electron-balanced." That is, there are 4 fewer electrons in two pyruvate molecules than there are in one glucose molecule. These electrons don't just float around the cell: they are carried by specific compounds called electron carriers. In glycolysis, the electron carrier of choice is nicotinamide adenine dinucleotide (NADH). To fix the electron imbalance, try clicking on the "Balance with NADH" link.

The full glycolysis reaction, including electron carriers and ATP production is:

Glucose + 2 NAD+ + 2 ADP + 2 Pi ⇌ 2 Pyruvate + 2 NADH + 2 ATP + 2 H2O

Clearly glycolysis produces ATP without any oxygen. However, if you ran glycolysis over and over again to provide ATP, the amount of NADH in the cell would grow continually. The ratio of NAD+ concentration to NADH concentration - sometimes called the "redox state" - is very important to living cells because it affects the energetics of redox reactions, in particular in glycolysis. The more NADH there is in the cell, the more energy is required to make more NADH. Therefore, if NADH is allowed to build up in the cell, glycolysis would release less and less energy.

Fermentation to lactate solves this problem by taking the electrons carried by NADH and giving them to pyruvate to form lactate:

2 Pyruvate + 2 NADH ⇌ 2 Lactate + 2 NAD+

Since lactate build-up is problematic (in much the same way that NADH build up is) the lactate is then excreted from the cell. Fermentation to lactate, then, produces 2 ATP from one glucose while forming 2 lactate:

Glucose + 2 ADP + 2 Pi ⇌ 2 Lactate + 2 ATP + 2 H2O

This neat biochemical trick enables organisms as varied as E. Coli and humans to produce energy from sugars even when oxygen isn't available.

Net Reactions of Major Cellular Pathways
Enzymatic Reactions in Glycolysis
Enzymatic Reactions in Central Metabolism