The Fate of a Candy Bar

When you metabolize food and thus obtain the ATP that powers your life, you employ both substrate-level phosphorylation and oxidative respiration. To get an overview of what goes on, it is instructive to follow the fate of something you eat and see what happens to it. Let us eat, then a chocolate bar. A chocolate bar, like many of the things that we consume, is a complex mixture of sugars lipids, proteins, and other molecules. The firs thing that happens in its journey toward production is that the complex molecules are degraded to simple ones. Disaccharides, such as sucrose, are split up into amino acids; and complex lipids are broken into smaller bits. These initial steps usually yield no more usable energy, but they serve to marshal the energy wealth of a diverse array of complex molecules into a small number of simple molecules, such as glucose. For simplicity, let us assume that our chocolate bar is entirely degraded to molecules of the six-carbon sugar glucose. Glucose occupies a central place in metabolism, since many different foodstuffs are converted to it. Glucose is where the making of ATP begins. The first stage of extracting energy from glucose is glycolysis. In glycolysis, ATP is generated in two ways. For each glucose molecule, two ATP molecules are expended in mobilizing the glucose molecule, four ATP molecules are formed by substrate-level phosphorylation, and four ATP molecules are formed by chemiosmosis, for a net yield of six ATP molecules. The third stage of extracting energy from glucose is the citric acid cycle. The three-carbon pyruvate molecule left over from glycolysis is the first oxidized in a second stage to a two-carbon molecule called acetyl-CoA, which feeds into the cycle. In the cycle, two more ATP molecules are extracted by substrate-level phosphorylation, and a large number of electrons and their subsequent use to drive chemiosmosis that leads to the greatest amount of ATP formation. When it is all over, the six-carbon glucose molecule has been cut up into six molecules of CO2 and 36 ATP molecules have been generated. This is a very good yield. Each ATP molecule represents the capture of 7.3 kcal/mole of energy, so 36 of them represents a total capture of 7.3 * 36 = 263 kcal/mole. The total energy content of the chemical bonds of glucose is only 686 kcal/mole, so we have succeeded in harvesting about 25% of the energy in gasoline into useful energy. This brief overview gives some sense of how cells organize their production of ATP. We will now examine glycolysis and the citric acid cycle as a processes, and study the ways in which they direct the flow of energy.

Glycolysis

1. Glucose is converted to two molecules of the three-carbon compound glyceraldehyde-3-phosphate (G3P), with the expenditure of ATP. 2. ATP is generated from the conversion of G3P to pyruvate. The 10 reactions of glycolysis proceed in four stages. Stage A: Three reactions change glucose into a compound that can readily be cleaved into three-carbon phosphorylatied units. Two of these reactions require the cleavage of an ATP molecule, so that this stage, glucose priming, requires the investment by the cell of two ATP molecules. Stage B: The second stage is cleavage and rearrangement, in which the six-carbon product of the first stage is split into two three-carbon molecules. One is G3P, and the other is converted to G3P by another reaction. Stage C: The third stage is oxidation, in which a pair of electrons is removed from G3P and donated to NAD+. NAD+ is a coenzyme that acts as an electron carrier in the cell, in this case accepting the two electrons from G3P to form NADH. Note that NAD+ is an ion, and that both electrons in the new covalent bond come from G3P. Stage D: The final stage, ATP generation, is composed of a series of four reactions that convert G3P into another three-carbon molecule, pyruvate, and in the process generate two ATP molecules. The glycolytic reaction sequence generates a small amount of ATP by reshuffling the bonds of glucose molecules. Glycolysis is a very inefficient process, capturing only about 2 % of the available chemical energy of glucose. Most of the remaining energy is unrecovered in the molecules that glycolysis procures, particularly pyruvate.

The Need to Close the Metabolic Circle

A catabolic process is one in which complex molecules are broken down into simpler ones; in contrast, an anabolic process is one in which more complex molecules are built up. 1. Oxidative respiration: Oxygen is an excellent electron acceptor, and in the presence of oxygen gas the hydrogen atom taken from G3P can (through a series of electron transfers) be donated to oxygen, forming water. This is what happens in your body. Because air is rich in oxygen, this is referred to as aerobic metabolism. 2. Fermentation: When oxygen is not available, another organic molecule can accept the hydrogen atom instead. Such a process is called fermentation. This is what happens, for example, when bacteria grow without oxygen, and is referred to as anaerobic metabolism, metabolism without oxygen.

Fermintation

In the absence of oxygen, cells donate the hydrogen atom generated by glycolysis to organic molecules in a process called fermentation. Acetaldehyde then accepts the hydrogen from NADH, producing NAD+ and ethyl alcohol, also called ethanol. In fermentations, which are anaerobic processes, the electrons generated in the glycolytic breakdown of glucose are donated to an oxidized organic molecule. In aerobic metabolism, in sharp contrast, such electrons are transferred to oxygen, generating ATP in the process.