Respiration might be redefined as the manufacture of ATP molecules, using organic fuel molecules as an energy source.

We know that the mechanics and energetic of the transformations ADP =ATP, let us focus our attention upon the sequence of events leading to the transfer of energy from the chemical bonds of nutrient materials into the high- energy phosphate bonds of ATP. All cells considered, the carbohydrate glucose is apparently the most common cellular nutrient, so let us use the catabolism of glucose to illustrate respiration.

It should be noted that this summary reaction is the reverse of that for photosynthesis, and like the overall photosynthetic reaction, it represents a vast number of separate reactions. In general, the respiration of glucose can be divided into two phases, the anaerobic and the aerobic.

Anaerobic respiration occurs in the absence of oxygen, whereas aerobic respiration occurs in the presence of oxygen. The aerobic phase of respiration is not observed in some organisms, due to the absence of enzymes necessary to catalyze certain specific reactions.

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In fact, 02 are actually poisonous to some cells. Furthermore, because of certain enzymatic differences in cells the end products of anaerobic respiration may differ somewhat. However, both anaerobic and aerobic respiration of glucose occurs in the cells of the more complex plants and animals.

There is also a difference with regard to the sites within a cell at which these respective types of respiration cue. Anaerobic respiration occurs in the general cytoplasm, whereas aerobic respiration is restricted to the mitochondria. From an energetic viewpoint, aerobic respiration results in a far greater transfer or energy- than anaerobic respiration; as consequences, ATP production is primarily associated with the aerobic phase.

The first reaction which glucose undergoes in the anaerobic pathway is a phosphorylation, by means of which glucose-6-phosphate is produced. This is an endergonic reaction, and in the reaction a molecules of ATP is dephosphorylated to ADP as the high-energy phosphate bond is transferred to glucose.

The glucose-6-phosphate undergoes an internal rearrangement by means of which it is transformed to fructose-6-phosphate. This compound undergoes an additional phosphorylation, resulting in the formation of fructose-, 6-phosphate.

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This is another endergonic reaction involving another ATP molecule. After this, a complex series of reactions occur during which two high-energy phosphate bonds are formed, two molecules of NAD are reduced to NAD.H2, and the six-carbon fructose-1, 6-diphospate is split into two three-carbon molecules of 1, 3-diphosphoglyceric acid.

Up to this point, obviously, the sequence of events is endergonic, not exergonic, as we would expect of a catabolic reaction. However, let us note that we have four phosphate groups in our two molecules of 1, 3-diphosphoglyceric acid, for which the cell “paid” only two ATP molecules. The other two phosphate groups came from inorganic phosphate.

Now the cell is ready to “cash in” on its “investment”. By a series of four steps, each molecule of 1, 3-diphosphoglyceric acid is divested of its phosphate groups and transformed into pyruvic acid. During the process, four molecules of ATP are generated, thus returning a net “profit” of two ATP’s to the cell. Pyruvic acid is the end product of this sequence of events, which is called the Embden-Meyerhof or glycolytic sequence.

What happens to the two hydrogen which was removed from the original glucose and is now held as NAD.H2? It remains in this state until it can be released to molecular oxygen by a series of oxidation reduction reactions.

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This is the usual pathway for hydrogen released in glycolysis, with pyretic acid being further degraded, and we shall give attention presently to this further aspect of catabolism. First, however, let us see what happens in a cell if the hydrogen produced in glycolysis cannot be given to gaseous oxygen. In most cells, this simply ties up all of the available nucleotide hydrogen acceptor with which it can combine.

The damming-up of hydrogen eventually poisons the cell. This explains why most organisms cannot live for very long in the absence of gaseous oxygen. However, there are cells and even organisms that are capable of living in a total absence of oxygen, that is, an aerobically.

Now lets us consider the two pyretic acid molecules which result from the glycolysis of a single glucose molecule. In aerobic respiration, you will recall, they are eventually oxidized to carbon dioxide and water.

This involved a complex series of reactions, and begins with the passage of pyretic acid into mitochondria. Here, a given molecule of pyretic acid is decarboxylated, and the remainder of the molecule is joined to a molecule of a substance called coenzyme A.

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The resulting compound, now containing only two carbon atoms of the original pyruvic acid, is called acetyl Co-A. The transformation of pyruvic acid to acetyl Co-A also involves a dehydrogenation, that is, two hydrogen’s are removed from each molecule.

Thus, two more electrons are available for transfer along the cytochrome oxidase system, which means that three more molecules of ATP are formed for each molecule of pyretic acid. This transformation, involving what is left of the original glucose molecule, may be illustrated in a highly abbreviated form as follows:

Each molecule of acetyl Co-A now enters a complex series of reactions which constitute a cycle. This cycle is called the Krebs cycle in honour of the biochemist A. A. Kebs, who worked out a major part of it, for which he was awarded the Nobel Prize in medicine in 1953.

It is also called the citric acid cycle because citric acid is usually considered the starting point in the cycle. This cycle is a common meeting point for all organic molecules which are utilized by the cell as fuel.

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It also furnishes carbon skeletons for a number of synthetic metabolic pathways. Since the series of reactions involved form a cycle, we can speak of a starting point in the cycle relative to the point at which it is entered by a given compound and of an endpoint or product relative to the point just preceding the point of entry.

The major reactions which occur in the Krebs cycle, from our viewpoint, are decarboxylations and dehydrogenations. All of the other reactions are simply preparatory to more decarboxylation and dehydrogenation. As a result of decarboxylation, the two remaining carbon atoms of the original pyruvic acid molecule are released as carbon dioxide, and as a result of dehydrogenation, the three remaining hydrogen atoms are passed along hydrogen transfer systems. This latter process, of course, leads to the generation of ATP.

Since the original glucose molecule is represented by two molecules of pyruvic acid, two molecules of acetyl Co-A, and so on, this means that four atoms of carbon are released as C02 in the Krebs cycle, and six atoms of hydrogen are available for transfer to molecular oxygen.

However, there is a net addition of three molecules of water to the Krebs cycle for each molecule of acetyl Co-A and this makes twelve additional hydrogen available for every two turns of the cycle.

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In all, then, twenty-four electrons are delivered to the cytochrome system for each one of the glucose molecules that undergoes complete respiration. How efficient is the cell in conserving the energy contained in a molecule of glucose?

If one considers that a gram-molecular weight of glucose contains about 690,000 calories of energy and that one high-energy phosphate bond contains about 10,000 calories, the cell has conserved about 55 per cent of the energy. Thermodynamically, this is a very high yield, and the cell is thus supplied with a form of chemical energy with which to drive endergonic reactions, transport molecules across cell membranes, accomplish colliery movement, and so on.

However, as ATP is changed back to ADP with the expenditure of high-energy phosphate bonds, there is further loss in efficiency, and in terms of useful activity, most cells probably realize far less than 55 percent efficiency from their fuels.