The principal substances from which cells extract energy are foodstuffs that react chemically with oxygen— carbohydrates, fats, and proteins. In the human body, essentially all carbohydrates are converted into glucose by the digestive tract and liver before they reach the other cells of the body. Similarly, proteins are converted into amino acids and fats are converted into fatty acids. Figure 1 shows oxygen and the foodstuffs—glucose, fatty acids, and amino acids—all entering the cell. Inside the cell, the foodstuffs react chemically with oxygen, under the influence of enzymes that control the reactions and channel the energy released in the proper direction. T he details of all these digestive and metabolic functions are provided in Chapters 63 through 73.

Fig1. Formation of adenosine triphosphate (ATP) in the  cell, showing that most of the ATP is formed in the mitochondria.  ADP, adenosine diphosphate; CoA, coenzyme A. 

Briefly, almost all these oxidative reactions occur inside the mitochondria, and the energy that is released is used to form the high-energy compound ATP. Then, ATP, not the original foodstuffs, is used throughout the cell to energize almost all of the subsequent intracellular metabolic reactions.

Functional Characteristics of ATP

ATP is a nucleotide composed of (1) the nitrogenous base adenine, (2) the pentose sugar ribose, and (3) three phosphate radicals. The last two phosphate radicals are connected with the remainder of the molecule by so-called highenergy phosphate bonds, which are represented in the formula shown by the symbol ~. Under the physical and chemical conditions of the body, each of these high energy bonds contains about 12,000 calories of energy per mole of ATP, which is many times greater than the energy stored in the average chemical bond, thus giving rise to the term highenergy bond. Further, the high-energy phosphate bond is very labile so that it can be split instantly on demand whenever energy is required to promote other intracellular reactions.

When ATP releases its energy, a phosphoric acid radical is split away and adenosine diphosphate (ADP) is formed. This released energy is used to energize many of the cell’s other functions, such as synthesis of substances and muscular contraction.

To reconstitute the cellular ATP as it is used up, energy derived from the cellular nutrients causes ADP and phosphoric acid to recombine to form new ATP, and the entire process is repeated over and over again. For these reasons, ATP has been called the energy currency of the cell because it can be spent and remade continually, having a turnover time of only a few minutes.

Chemical Processes in the Formation of ATP—Role of the Mitochondria. Upon entry into the cells, glucose is subjected to enzymes in the cytoplasm that convert it into pyruvic acid (a process called glycolysis). A small amount of ADP is changed into ATP by the energy released during this conversion, but this amount accounts for less than 5 percent of the overall energy metabolism of the cell.

About 95 percent of the cell’s ATP formation occurs in the mitochondria. The pyruvic acid derived from carbo hydrates, fatty acids from lipids, and amino acids from proteins is eventually converted into the compound acetyl coenzyme A (CoA) in the matrix of mitochondria. This substance, in turn, is further dissoluted (for the purpose of extracting its energy) by another series of enzymes in the mitochondrion matrix, undergoing dis solution in a sequence of chemical reactions called the citric acid cycle, or Krebs cycle. These chemical reactions are so important that they are explained in detail in Chapter 68.

In this citric acid cycle, acetyl-CoA is split into its component parts, hydrogen atoms and carbon dioxide. The carbon dioxide diffuses out of the mitochondria and eventually out of the cell; finally, it is excreted from the body through the lungs.

The hydrogen atoms, conversely, are highly reactive, and they combine with oxygen that has also diffused into the mitochondria. This combination releases a tremendous amount of energy, which is used by the mitochondria to convert large amounts of ADP to ATP. The processes of these reactions are complex, requiring the participation of many protein enzymes that are integral parts of mitochondrial membranous shelves that protrude into the mitochondrial matrix. The initial event is removal of an electron from the hydrogen atom, thus converting it to a hydrogen ion. The terminal event is combination of hydrogen ions with oxygen to form water plus release of tremendous amounts of energy to large globular proteins that protrude like knobs from the membranes of the mitochondrial shelves; this process is called ATP synthetase. Finally, the enzyme ATP synthetase uses the energy from the hydrogen ions to cause the conversion of ADP to ATP. The newly formed ATP is transported out of the mitochondria into all parts of the cell cytoplasm and nucleoplasm, where its energy is used to energize multiple cell functions.

This overall process for formation of ATP is called the chemiosmotic mechanism of ATP formation. The chemical and physical details of this mechanism are presented in Chapter 68, and many of the detailed metabolic functions of ATP in the body are presented in Chapters 68 through 72.

Uses of ATP for Cellular Function. Energy from ATP is used to promote three major categories of cellular functions: (1) transport of substances through multiple mem branes in the cell, (2) synthesis of chemical compounds throughout the cell, and (3) mechanical work. These uses of ATP are illustrated by examples in Figure 2: (1) to supply energy for the transport of sodium through the cell membrane, (2) to promote protein synthesis by the ribosomes, and (3) to supply the energy needed during muscle contraction.

Fig2. Use of adenosine triphosphate (ATP; formed in the  mitochondrion) to provide energy for three major cellular functions:  membrane transport, protein synthesis, and muscle contraction.  ADP, adenosine diphosphate. 

In addition to membrane transport of sodium, energy from ATP is required for membrane transport of potassium ions, calcium ions, magnesium ions, phosphate ions, chloride ions, urate ions, hydrogen ions, and many other ions and various organic substances. Membrane trans port is so important to cell function that some cells—the renal tubular cells, for instance—use as much as 80 percent of the ATP that they form for this purpose alone.

In addition to synthesizing proteins, cells make phospholipids, cholesterol, purines, pyrimidines, and a host of other substances. Synthesis of almost any chemical com pound requires energy. For instance, a single protein molecule might be composed of as many as several thousand amino acids attached to one another by peptide linkages. The formation of each of these linkages requires energy derived from the breakdown of four high-energy bonds; thus, many thousand ATP molecules must release their energy as each protein molecule is formed. Indeed, some cells use as much as 75 percent of all the ATP formed in the cell simply to synthesize new chemical compounds, especially protein molecules; this is particularly true during the growth phase of cells.

The final major use of ATP is to supply energy for special cells to perform mechanical work. We see in Chapter 6 that each contraction of a muscle fiber requires expenditure of tremendous quantities of ATP energy. Other cells perform mechanical work in other ways, especially by ciliary and ameboid motion, described later in this chapter. The source of energy for all these types of mechanical work is ATP.

In summary, ATP is always available to release its energy rapidly and almost explosively wherever in the cell it is needed. To replace the ATP used by the cell, much slower chemical reactions break down carbohydrates, fats, and proteins and use the energy derived from these processes to form new ATP. More than 95 percent of this ATP is formed in the mitochondria, which accounts for the mitochondria being called the “powerhouses” of the cell.