2.4 Redox Reactions and Glycolysis

Oxidation is loss of electrons; reduction is gain of electrons. In many biological molecules, loss of hydrogen or gain of oxygen signals oxidation, while gain of hydrogen or loss of oxygen signals reduction. Because an electron lost by one substance must be accepted by another, oxidation and reduction are coupled in a redox reaction. Glucose is progressively oxidized during respiration, while oxygen is ultimately reduced to water.

NAD acts as an electron and hydrogen carrier. A dehydrogenase removes hydrogen from a substrate; NAD accepts electrons and a proton to become reduced NAD, commonly written NADH + H⁺ in this course. The reduced carrier can later donate high-energy electrons to an electron transport chain. Writing NADH₂ hides the proton and electron bookkeeping and should be avoided.

First, two ATP phosphorylate glucose, producing a hexose bisphosphate. Phosphorylation increases the molecule's energy and makes it less stable, preparing it for cleavage. The initial ATP cost is an investment: without it, subsequent reactions would not yield ATP at a useful rate.

Second, lysis splits the six-carbon phosphorylated sugar into two three-carbon triose phosphates. From this point onward, every described event occurs twice per glucose. This doubling is the source of many accounting errors: a single triose may yield two ATP later, but two trioses yield four.

Third, each triose phosphate is oxidized. NAD is reduced, and an additional inorganic phosphate is incorporated into an energy-rich intermediate. Fourth, phosphate groups are transferred from intermediates directly to ADP, forming ATP by substrate-level phosphorylation. Four ATP are produced in the payoff phase; subtracting the two invested leaves a net gain of two.

The final products per glucose are two pyruvate, two net ATP and two reduced NAD. Glycolysis releases no carbon dioxide because all six carbons remain in the two pyruvate molecules. Oxygen does not appear as a glycolysis reactant, yet oxygen availability indirectly determines whether reduced NAD can be reoxidized through the mitochondrial electron transport chain.

Much of respiratory ATP ultimately comes from electrons associated with carbon–hydrogen bonds. Fatty acids are more reduced and contain proportionally more C–H bonds and less oxygen than carbohydrates. Their oxidation therefore supplies more reduced carriers and yields more energy per gram. This is a chemical explanation for lipid energy density, not a claim that fats enter glycolysis unchanged.

The products of lipid and amino-acid breakdown can enter respiration at different points. Glycerol can feed into glycolytic intermediates, fatty acids are converted to acetyl CoA, and some amino-acid carbon skeletons enter the Krebs cycle after removal of amino groups. Glucose is the standard model substrate, but cellular respiration is a convergent network rather than a glucose-only tube.