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Obviously, energy must be infused into the system to regenerate ATP. Where does this energy come from? In nearly every living thing on earth, the energy comes from the metabolism of glucose. In this way, ATP is a direct link between the limited set of exergonic pathways of glucose catabolism and the multitude of endergonic pathways that power living cells.


Recall that, in some chemical reactions, enzymes may bind to several substrates that react with each other on the enzyme, forming an intermediate complex. An intermediate complex is a temporary structure, and it allows one of the substrates (such as ATP) and reactants to more readily react with each other; in reactions involving ATP, ATP is one of the substrates and ADP is a product. During an endergonic chemical reaction, ATP forms an intermediate complex with the substrate and enzyme in the reaction. This intermediate complex allows the ATP to transfer its third phosphate group, with its energy, to the substrate, a process called phosphorylation. Phosphorylation refers to the addition of the phosphate (~P). This is illustrated by the following generic reaction:

A + enzyme + ATP   [  enzyme    P ]    B + enzyme + ADP + phosphate ion

When the intermediate complex breaks apart, the energy is used to modify the substrate and convert it into a product of the reaction. The ADP molecule and a free phosphate ion are released into the medium and are available for recycling through cell metabolism.

Substrate phosphorylation

ATP is generated through two mechanisms during the breakdown of glucose. A few ATP molecules are generated (that is, regenerated from ADP) as a direct result of the chemical reactions that occur in the catabolic pathways. A phosphate group is removed from an intermediate reactant in the pathway, and the free energy of the reaction is used to add the third phosphate to an available ADP molecule, producing ATP ( [link] ). This very direct method of phosphorylation is called substrate-level phosphorylation    .

This illustration shows a substrate-level phosphorylation reaction in which the gamma phosphate of ATP is attached to a protein.
In phosphorylation reactions, the gamma phosphate of ATP is attached to a protein.

Oxidative phosphorylation

Most of the ATP generated during glucose catabolism, however, is derived from a much more complex process, chemiosmosis, which takes place in mitochondria ( [link] ) within a eukaryotic cell or the plasma membrane of a prokaryotic cell. Chemiosmosis , a process of ATP production in cellular metabolism, is used to generate 90 percent of the ATP made during glucose catabolism and is also the method used in the light reactions of photosynthesis to harness the energy of sunlight. The production of ATP using the process of chemiosmosis is called oxidative phosphorylation    because of the involvement of oxygen in the process.

This illustration shows the structure of a mitochondrion, which has an outer membrane and an inner membrane. The inner membrane has many folds, called cristae. The space between the outer membrane and the inner membrane is called the intermembrane space, and the central space of the mitochondrion is called the matrix. ATP synthase enzymes and the electron transport chain are located in the inner membrane
In eukaryotes, oxidative phosphorylation takes place in mitochondria. In prokaryotes, this process takes place in the plasma membrane. (Credit: modification of work by Mariana Ruiz Villareal)

Career connections

Mitochondrial disease physician

What happens when the critical reactions of cellular respiration do not proceed correctly? Mitochondrial diseases are genetic disorders of metabolism. Mitochondrial disorders can arise from mutations in nuclear or mitochondrial DNA, and they result in the production of less energy than is normal in body cells. In type 2 diabetes, for instance, the oxidation efficiency of NADH is reduced, impacting oxidative phosphorylation but not the other steps of respiration. Symptoms of mitochondrial diseases can include muscle weakness, lack of coordination, stroke-like episodes, and loss of vision and hearing. Most affected people are diagnosed in childhood, although there are some adult-onset diseases. Identifying and treating mitochondrial disorders is a specialized medical field. The educational preparation for this profession requires a college education, followed by medical school with a specialization in medical genetics. Medical geneticists can be board certified by the American Board of Medical Genetics and go on to become associated with professional organizations devoted to the study of mitochondrial diseases, such as the Mitochondrial Medicine Society and the Society for Inherited Metabolic Disease.

Section summary

ATP functions as the energy currency for cells. It allows the cell to store energy briefly and transport it within the cell to support endergonic chemical reactions. The structure of ATP is that of an RNA nucleotide with three phosphates attached. As ATP is used for energy, a phosphate group or two are detached, and either ADP or AMP is produced. Energy derived from glucose catabolism is used to convert ADP into ATP. When ATP is used in a reaction, the third phosphate is temporarily attached to a substrate in a process called phosphorylation. The two processes of ATP regeneration that are used in conjunction with glucose catabolism are substrate-level phosphorylation and oxidative phosphorylation through the process of chemiosmosis.

Questions & Answers

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