Biochemical Pathways—Cellular Respiration

By Enger, E.D., Ross, F.C., Bailey, D.B.

Edited by Paul Ducham

ENERGY AND ORGANISMS

There are hundreds of different chemical reactions taking place within the cells of organisms. Many of these reactions are involved in providing energy for the cells. Organisms are classified into groups based on the kind of energy they use. Organisms that are able to use basic energy sources, such as sunlight, to make energy-containing organic molecules from inorganic raw materials are called autotrophs (auto = self; troph = feeding). There are also prokaryotic organisms that use inorganic chemical reactions as a source of energy to make larger, organic molecules. This process is known as chemosynthesis. Therefore, there are at least two kinds of autotrophs: Those that use light are called photosynthetic autotrophs and those that use inorganic chemical reactions are called chemosynthetic autotrophs. All other organisms require organic molecules as food and are called heterotrophs (hetero = other; troph = feeding). Heterotrophs get their energy from the chemical bonds of food molecules, such as carbohydrates, fats, and proteins, which they must obtain from their surroundings.
Within eukaryotic cells, certain biochemical processes are carried out in specific organelles. Chloroplasts are the sites of photosynthesis, and mitochondria are the sites of most of the reactions of cellular respiration (figure 6.1). Because prokaryotic cells lack mitochondria and chloroplasts, they carry out photosynthesis and cellular respiration within the cytoplasm or on the inner surfaces of the cell membrane or on other special membranes. Table 6.1 provides a summary of the concepts just discussed and how they are related to one another.
This article will focus on the reactions involved in the processes of cellular respiration. In cellular respiration, organisms control the release of chemical-bond energy from large, organic molecules and use the energy for the many activities necessary to sustain life. All organisms, whether autotrophic or heterotrophic, must carry out cellular respiration if they are to survive. Because nearly all organisms use organic molecules as a source of energy, they must obtain these molecules from their environment or manufacture these organic molecules, which they will later break down. Thus, photosynthetic organisms produce food molecules, such as carbohydrates, for themselves as well as for all the other organisms that feed on them. There are many variations of cellular respiration. Some organisms require the presence of oxygen for these processes, called aerobic processes. Other organisms carry out a form of respiration that does not require oxygen; these processes are called anaerobic.

Figure 6.1

Table 6.1

AN OVERVIEW OF AEROBIC CELLULAR RESPIRATION

Aerobic cellular respiration is a specific series of enzymecontrolled chemical reactions in which oxygen is involved in the breakdown of glucose into carbon dioxide and water and the chemical-bond energy from glucose is released to the cell in the form of ATP. Although the actual process of aerobic cellular respiration involves many enzyme-controlled steps, the net result is that a reaction between sugar and oxygen results in the formation of carbon dioxide and water with the release of energy. The following equation summarizes this process:

Image 1

Covalent bonds are formed by atoms sharing pairs of fast-moving, energetic electrons. Therefore, the covalent bonds in the sugar glucose contain chemical potential energy. Of all the covalent bonds in glucose (O—H, C—H, C—C), those easiest to get at are the C—H and O—H bonds on the outside of the molecule. When these bonds are broken, two things happen:

1. The energy of the electrons can ultimately be used to phosphorylate ADP molecules to produce higher-energy ATP molecules.
2. Hydrogen ions (protons) are released. The ATP is used to power the metabolic activities of the cell. The chemical activities that remove electrons from glucose result in the glucose being oxidized.

These high-energy electrons must be controlled. If they were allowed to fly about at random, they would quickly combine with other molecules, causing cell death. Electrontransfer molecules, such as NAD+and FAD, temporarily hold the electrons and transfer them to other electron-transfer molecules. ATP is formed when these transfers take place. Once energy has been removed from electrons for ATP production, the electrons must be placed in a safe location. In aerobic cellular respiration, these electrons are ultimately attached to oxygen. Oxygen serves as the final resting place of the less energetic electrons. When the electrons are added to oxygen, it becomes a negatively charged ion, O.
Because the oxygen has gained electrons, it has been reduced. Thus, in the aerobic cellular respiration of glucose, glucose is oxidized and oxygen is reduced. If something is oxidized (loses electrons), something else must be reduced (gains electrons). A molecule cannot simply lose its electrons—they have to go someplace! Eventually, the positively charged hydrogen ions (H+.) that were released from the glucose molecule combine with the negatively charged oxygen ion (O=) to form water (H2O).
As all the hydrogens are stripped off the glucose molecule, the remaining carbon and oxygen atoms are rearranged to form individual molecules of CO2. All the hydrogen originally a part of the glucose has been moved to the oxygen to form water. All the remaining carbon and oxygen atoms of the original glucose are now in the form of CO2. The energy released from this process is used to generate ATP (figure 6.2).
In cells, these reactions take place in a particular order and in particular places within the cell. In eukaryotic cells, the process of releasing energy from food molecules begins in the cytoplasm and is completed in the mitochondrion. There are three distinct enzymatic pathways involved (figure 6.3): glycolysis, the Krebs cycle, and the electron-transport system.

Figure 6.2

Figure 6.3

GLYCOLYSIS

Glycolysis (glyco = sugar; lysis = to split) is a series of enzyme-controlled, anaerobic reactions that takes place in the cytoplasm of cells, which results in the breakdown of glucose with the release of electrons and the formation of ATP. During glycolysis, the 6-carbon sugar glucose is split into two smaller, 3-carbon molecules, which undergo further modification to form pyruvic acid or pyruvate.1 Enough energy is released to produce two ATP molecules. Some of the bonds holding hydrogen atoms to the glucose molecule are broken, and the electrons are picked up by electron carrier molecules (NAD) and transferred to a series of electron-transfer reactions known as the electron-transport system (ETS).

THE KREBS CYCLE

The Krebs cycle is a series of enzyme-controlled reactions that takes place inside the mitochondrion, which completes the breakdown of pyruvic acid with the release of carbon dioxide, electrons, and ATP. During the Krebs cycle, the pyruvic acid molecules produced from glycolysis are further broken down. During these reactions, the remaining hydrogens are removed from the pyruvic acid, and their electrons are picked up by the electron carriers NAD+

THE ELECTRON-TRANSPORT SYSTEM (ETS)

The electron-transport system (ETS) is a series of enzymecontrolled reactions that converts the kinetic energy of hydrogen electrons to ATP. The electrons are carried to the electron-transport system from glycolysis and the Krebs cycle by NADH and FADH2. The electrons are transferred through a series of oxidation-reduction reactions involving enzymes until eventually the electrons are accepted by oxygen atoms to form oxygen ions (O=

FUNDAMENTAL DESCRIPTION

Glycolysis Glycolysis is a series of enzyme-controlled reactions that takes place in the cytoplasm. During glycolysis, a 6-carbon sugar molecule (glucose) has energy added to it from two ATP molecules. Adding this energy makes some of the bonds of the glucose molecule unstable, and the glucose molecule is more easily broken down. After passing through several more enzymecontrolled reactions, the 6-carbon glucose is broken down to two 3-carbon molecules known as glyceraldehyde-3-phosphate (also known as phosphoglyceraldehyde2), which undergo additional reactions to form pyruvic acid (CH3COCOOH).
Enough energy is released by this series of reactions to produce four ATP molecules. Because two ATP molecules were used to start the reaction and four were produced, there is a net gain of two ATPs from the glycolytic pathway (figure 6.4). During the process of glycolysis, some hydrogens and their electrons are removed from the organic molecules being processed and picked up by the electron-transfer molecule NAD+to form NADH. Enough hydrogens are released during glycolysis to form 2 NADHs. The NADH with its extra electrons contains a large amount of potential energy, which can be used to make ATP in the electron-transport system. The job of the coenzyme NAD+is to transport these energy-containing electrons and protons safely to the electrontransport system. Once they have dropped off their electrons, the oxidized NAD+s are available to pick up more electrons and repeat the job. The following is a generalized reaction that summarizes the events of glycolysis:

Image 2

The Krebs Cycle
The series of reactions known as the Krebs cycle takes place within the mitochondria of cells. It gets its name from its discoverer, Hans Krebs, and the fact that the series of reactions begins and ends with the same molecule. The Krebs cycle is also known as the citric acid cycle and the TriCarboxylic Acid cycle (TCA). The 3-carbon pyruvic acid molecules released from glycolysis enter the mitochondria, are acted upon by specific enzymes, and are converted to 2-carbon acetyl molecules. At the time the acetyl is produced, 2 hydrogens are attached to NAD+ to form NADH. The carbon atom that was removed is released as carbon dioxide. The acetyl molecule is attached to coenzyme A (CoA) and proceeds through the Krebs cycle. During the Krebs cycle (figure 6.5), the acetyl is completely oxidized.
The remaining hydrogens and their electrons are removed. Most of the electrons are picked up by NAD+to form NADH, but at one point in the process FAD picks up electrons to form FADH2. Regardless of which electron carrier is being used, the electrons are sent to the electron-transport system. The remaining carbon and oxygen atoms are combined to form CO2. As in glycolysis, enough energy is released to generate 2 ATP molecules. At the end of the Krebs cycle, the acetyl has been completely broken down (oxidized) to CO2. The energy in the molecule has been transferred to ATP, NADH, or FADH2.. Also, some of the energy has been released as heat. For each of the acetyl molecules that enters the Krebs cycle, 1 ATP, 3 NADHs, and 1 FADH2 are produced. If we count the NADH produced during glycolysis, when acetyl was formed, there are a total of 4 NADHs for each pyruvic acid that enters a mitochondrion. The following is a generalized equation that summarizes those reactions:

Image 3

The Electron-Transport System
Of the three steps of aerobic cellular respiration, (glycolysis, Krebs cycle, and electron-transport system) cells generate the greatest amount of ATP from the electron-transport system (figure 6.6). During this stepwise sequence of oxidationreduction reactions, the energy from the NADH and FADH2. molecules generated in glycolysis and the Krebs cycle is used to produce ATP. Iron-containing cytochrome (cyto = cell; chrom = color) enzyme molecules are located on the membranes of the mitochondrion. The energy-rich electrons are passed (transported) from one cytochrome to another, and the energy is used to pump protons (hydrogen ions) from one side of the membrane to the other. The result of this is a higher concentration of hydrogen ions on one side of the membrane. As the concentration of hydrogen ions increases on one side, a proton gradient builds up. Because of this concentration gradient, when a membrane channel is opened, the protons flow back to the side from which they were pumped. As they pass through the channels, a phosphorylase enzyme (ATP synthetase, also referred to as ATPase) speeds the formation of an ATP molecule by bonding a phosphate to an ADP molecule (phosphorylation). When all the electrons and hydrogen ions are accounted for, a total of 32 ATPs are formed from the electrons and hydrogens removed from the original glucose molecule. The hydrogens are then bonded to oxygen to form water.

Figure 6.4

Figure 6.5

Figure 6.6

DETAILED DESCRIPTION

Glycolysis The first stage of the cellular respiration process takes place in the cytoplasm. This first step, known as glycolysis, consists of the enzymatic breakdown of a glucose molecule without the use of molecular oxygen. Because no oxygen is required, glycolysis is called an anaerobic process. The glycolysis pathway can be divided into two general sets of reactions. The first reactions make the glucose molecule unstable, and later oxidation-reduction reactions are used to synthesize ATP and capture hydrogens.
Some energy must be added to the glucose molecule in order to start glycolysis, because glucose is a very stable molecule and will not automatically break down to release energy. In glycolysis, the initial glucose molecule gains a phosphate to become glucose-6-phosphate, which is converted to fructose-6-phosphate. When a second phosphate is added, fructose-1, 6-bisphosphate (P—C6—P) is formed. This 6-carbon molecule is unstable and breaks apart to form two 3-carbon, glyceraldehyde-3-phosphate molecules.
Each of the two glyceraldehyde-3-phosphate molecules acquires a second phosphate from a phosphate supply normally found in the cytoplasm. Each molecule now has 2 phosphates attached, 1, 3 isphosphoglycerate 1, 3-bisphosphoglycerate (P—C3—P). A series of reactions follows, in which energy is released by breaking chemical bonds that hold the phosphates to 1,3 bisphosphoglycerate. The energy and the phosphates are used to produce ATP. Since there are 2 1,3 bisphosphoglycerate each with 2 phosphates, a total of 4 ATPs are produced. Because 2 ATPs were used to start the process, a net yield of 2 ATPs results. In addition, 4 hydrogen atoms detach from the carbon skeleton and their electrons are transferred to NAD+to form NADH, which transfers the electrons to the electron-transport system. The 3-carbon pyruvic acid molecules that remain are the raw material for the Krebs cycle. Because glycolysis occurs in the cytoplasm and the Krebs cycle takes place inside mitochondria, the pyruvic acid must enter the mitochondrion before it can be broken down further.
In summary, the process of glycolysis takes place in the cytoplasm of a cell, where glucose (C6H12O6) enters a series of reactions that

1. Requires the use of 2 ATPs
2. Ultimately results in the formation of 4 ATPs
3. Results in the formation of 2 NADHs
4. Results in the formation of 2 molecules of pyruvic acid (CH3COCOOH)

Because 2 molecules of ATP are used to start the process and a total of 4 ATPs are generated, each glucose molecule that undergoes glycolysis produces a net yield of 2 ATPs (Figure 6.7).

The Krebs Cycle
After pyruvate (pyruvic acid) enters the mitochondrion, it is first acted upon by an enzyme, along with a molecule known as coenzyme A (CoA) (figure 6.8). This results in three significant products. Hydrogen atoms are removed and NADH is formed, a carbon is removed and carbon dioxide is formed, and a 2-carbon acetyl molecule is formed, which temporarily attaches to coenzyme A to produce acetyl-coenzyme A. (These and subsequent reactions of the Krebs cycle take place in the fluid between the membranes of the mitochondrion.) The acetyl coenzyme A enters the series of reactions known as the Krebs cycle. During the Krebs cycle, the acetyl is systematically dismantled. Its hydrogen atoms are removed and the remaining carbons are released as carbon dioxide.
The first step in this process involves the acetyl coenzyme A. The acetyl portion of the complex is transferred to a 4-carbon compound called oxaloacetate (oxaloacetic acid) and a new 6-carbon citrate molecule (citric acid) is formed. The coenzyme A is released to participate in another reaction with pyruvic acid. This newly formed citrate is broken down in a series of reactions, which ultimately produces oxaloacetate, which was used in the first step of the cycle (hence, the names Krebs cycle, citric acid cycle, and tricarboxylic acid cycle). The compounds formed during this cycle are called keto acids.
In the process, electrons are removed and, along with protons, become attached to the coenzymes NAD+and FAD. Most become attached to NAD+but some become attached to FAD. As the molecules move through the Krebs cycle, enough energy is released to allow the synthesis of 1 ATP molecule for each acetyl that enters the cycle. The ATP is formed from ADP and a phosphate already present in the mitochondria. For each pyruvate molecule that enters a mitochondrion and is processed through the Krebs cycle, 3 carbons are released as 3 carbon dioxide molecules, 5 pairs of hydrogen atoms are removed and become attached to NAD+or FAD, and 1 ATP molecule is generated. When both pyruvate molecules have been processed through the Krebs cycle, (1) all the original carbons from the glucose have been released into the atmosphere as 6 carbon dioxide molecules; (2) all the hydrogen originally found on the glucose has been transferred to either NAD+or FAD to form NADH or FADH2; and (3) 2 ATPs have been formed from the addition of phosphates to ADPs (review figure 6.8).
In summary, the Krebs cycle takes place within the mitochondria. For each pyruvate molecule that enters the Krebs cycle:
1. The three carbons of the pyruvate are released as carbon dioxide (CO2).
2. Five pairs of hydrogens become attached to hydrogen carriers to become 4 NADHs and 1 FADH2.
3. One ATP is generated.

The Electron-Transport System
The series of reactions in which energy is transferred from the electrons and protons carried by NADH and FADH2 is known as the electron-transport system (ETS) (figure 6.9). This is the final stage of aerobic cellular respiration and is dedicated to generating ATP. The reactions that make up the electron-transport system are a series of oxidationreduction reactions in which the electrons are passed from one electron carrier molecule to another until ultimately they are accepted by oxygen atoms. The negatively charged oxygen combines with the hydrogen ions to form water. It is this step that makes the process aerobic. Keep in mind that potential energy increases whenever things experiencing a repelling force are pushed together, such as adding the third phosphate to an ADP molecule. Potential energy also increases whenever things that attract each other are pulled apart, as in the separation of the protons from the electrons.
Let’s now look in just a bit more detail at what happens to the electrons and protons that are carried to the electrontransport systems by NADH and FADH2 and how these activities are used to produce ATP. The mitochondrion consists of two membranes—an outer, enclosing membrane and an inner, folded membrane. The reactions of the ETS are associated with this inner membrane. Within the structure of the membrane are several enzyme complexes, which perform particular parts of the ETS reactions (review figure 6.9). The production of ATPs involves two separate but connected processes. Electrons carried by NADH enter reactions in enzyme complex I, where they lose some energy and are eventually picked up by a coenzyme (coenzyme Q). Electrons from FADH2 enter enzyme complex II and also are eventually transferred to coenzyme Q. Coenzyme Q transfers the electrons to enzyme complex III. In complex III, the electrons lose additional energy and are transferred to cytochrome c, which transfers electrons to enzyme complex IV. In complex IV, the electrons are eventually transferred to oxygen. As the electrons lose energy in complex I, complex III, and complex IV, additional protons are pumped into the intermembrane space. When these protons flow down the concentration gradient through channels in the membrane, phosphorylase enzymes (ATPase) in the membrane are able to use the energy to generate ATP.
A total of 12 pairs of electrons and hydrogens are transported to the ETS from glycolysis and the Krebs cycle for each glucose that enters the process. In eukaryotic organisms, the pairs of electrons can be accounted for as follows: 2 pairs are carried by NADH and were generated during glycolysis outside the mitochondrion, 8 pairs are carried as NADH and were generated within the mitochondrion, and 2 pairs are carried by FADH2 and were generated within the mitochondrion.
    • For each of the 8 NADHs generated within the mitochondrion, enough energy is released to produce 3 ATP molecules. Therefore, 24 ATPs are released from these
       
electrons carried by NADH.               
   • In eukaryotic cells, the electrons released during glycolysis are carried by NADH and converted to 2 FADH2 in order to shuttle them into the mitochondria. Once they are inside the mitochondria, they follow the same pathway as the other 2 FADH2s from the Krebs cycle.
The electrons carried by FADH2 are lower in energy. When these electrons go through the series of oxidationreduction reactions, they release enough energy to produce a total of 8 ATPs. Therefore, a total of 32 ATPs are produced from the hydrogen electrons that enter the ETS.
Finally, a complete accounting of all the ATPs produced during all three parts of aerobic cellular respiration results in a total of 36 ATPs: 32 from the ETS, 2 from glycolysis, and 2 from the Krebs cycle.
In summary, the electron-transport system takes place within the mitochondrion, where
1. Oxygen is used up as the oxygen atoms receive the hydrogens from NADH and FADH2 to form water (H2O).
2. NAD+and FAD are released, to be used over again.
3. Thirty-two ATPs are produced.

Figure 6.7

Figure 6.8

Figure 6.9

AEROBIC CELLULAR RESPIRATION IN PROKARYOTES

The discussion so far in this article has dealt with the process of aerobic cellular respiration in eukaryotic organisms. However, some prokaryotes also use aerobic cellular respiration. Because prokaryotes do not have mitochondria, there are some differences between what they do and what eukaryotes do. The primary difference involves the electrons carried from glycolysis to the electron-transport system. In eukaryotes, the electrons released during glycolysis are carried by NADH and transferred to FAD to form FADH2 in order to get the electrons across the outer membrane of the mitochondrion. Because FADH2 results in the production of fewer ATPs than NADH, there is a cost to the eukaryotic cell of getting the electrons into the mitochondrion. This transfer is not necessary in prokaryotes, so they are able to produce a theoretical 38 ATPs for each glucose metabolized, rather than the 36 ATPs produced by eukaryotes (table 6.2).

Table 6.2

ALCOHOLIC FERMENTATION

Alcoholic fermentation is the anaerobic respiration pathway that yeast cells follow when oxygen is lacking in their environment. In this pathway, the pyruvic acid is converted to ethanol (a 2-carbon alcohol, C2H5OH) and carbon dioxide. Yeast cells then are able to generate only 4 ATPs from glycolysis. The cost for glycolysis is still 2 ATPs; thus, for each glucose a yeast cell oxidizes, it profits by 2 ATPs.
Although during alcoholic fermentation yeasts get ATP and discard the waste products ethanol and carbon dioxide, these waste products are useful to humans. In making bread, the carbon dioxide is the important end product; it becomes trapped in the bread dough and makes it rise—the bread is leavened. Dough that has not undergone this process is called unleavened. The alcohol produced by the yeast evaporates during the baking process. In the brewing industry, ethanol is the desirable product produced by yeast cells. Champagne, other sparkling wines, and beer are products that contain both carbon dioxide and alcohol. The alcohol accumulates, and the carbon dioxide in the bottle makes them sparkling (bubbly) beverages. In the manufacture of many wines, the carbon dioxide is allowed to escape, so these wines are not sparkling; they are called “still” wines.

LACTIC ACID FERMENTATION

In lactic acid fermentation, the pyruvic acid (CH3COCOOH) that results from glycolysis is converted to lactic acid (CH3CHOHCOOH) by the transfer of electrons that had been removed from the original glucose. In this case, the net profit is again only 2 ATPs per glucose. The buildup of the waste product, lactic acid, eventually interferes with normal metabolic functions and the bacteria die. The lactic acid waste product from these types of anaerobic bacteria are used to make yogurt, cultured sour cream, cheeses, and other fermented dairy products. The lactic acid makes the milk protein coagulate and become puddinglike or solid. It also gives the products their tart flavor, texture, and aroma. In the human body, different cells have different metabolic capabilities. Nerve cells must have a constant supply of oxygen to conduct aerobic cellular respiration. Red blood cells lack mitochondria and must rely on the anaerobic process of lactic acid fermentation to provide themselves with energy. Muscle cells can do either. As long as oxygen is available to skeletal muscle cells, they function aerobically. However, when oxygen is unavailable—because of long periods of exercise or heart or lung problems that prevent oxygen from getting to the skeletal muscle cells—the cells make a valiant effort to meet energy demands by functioning anaerobically. While skeletal muscle cells are functioning anaerobically, they accumulate lactic acid. This lactic acid must ultimately be metabolized, which requires oxygen. Therefore, the accumulation of lactic acid represents an oxygen debt, which must be repaid in the future. It is the lactic acid buildup that makes muscles tired when we exercise. When the lactic acid concentration becomes great enough, lactic acid fatigue results. As a person cools down after a period of exercise, breathing and heart rate stay high until the oxygen debt is repaid and the level of oxygen in the muscle cells returns to normal. During this period, the lactic acid that has accumulated is converted back into pyruvic acid. The pyruvic acid can then continue through the Krebs cycle and the ETS as oxygen becomes available. In addition to what is happening in the muscles, much of the lactic acid is transported by the bloodstream to the liver, where about 20% is metabolized through the Krebs cycle and 80% is resynthesized into glucose.

FAT RESPIRATION

A triglyceride (also known as a neutral fat) is a large molecule that consists of a molecule of glycerol with 3 fatty acids attached to it. Before these fats can be broken down to release energy, they must be converted to smaller units by digestive processes. Several enzymes are involved in these steps. The first step is to break the bonds between the glycerol and the fatty acids. Glycerol is a 3-carbon molecule that is converted into glyceraldehyde-3-phosphate. Because glyceraldehyde-3-phosphate is involved in one of the steps in glycolysis, it can enter the glycolysis pathway (figure 6.11). The remaining fatty acids are often long molecules (typically 14 to 20 carbons long), which also must be processed before they can be further metabolized. First, they need to enter the mitochondrion, where subsequent reactions take place. Once inside the mitochondrion, each long chain of carbons that makes up the carbon skeleton is hydrolyzed (split by the addition of a water molecule) into 2-carbon fragments. Next, each of the 2-carbon fragments is converted into acetyl. The acetyl molecules are carried into the Krebs cycle by coenzyme A molecules. Once in the Krebs cycle, they proceed through the Krebs cycle just like the acetyls from glucose.
By following the glycerol and each 2-carbon fragment through the cycle, you can see that each molecule of fat has the potential to release several times as much ATP as does a molecule of glucose. Each glucose molecule has 6 pairs of hydrogen, whereas a typical molecule of fat has up to 10 times that number. This is why fat makes such a good long-term energy storage material. It is also why it takes so long for people on a weight-reducing diet to remove fat. It takes time to use all the energy contained in the fatty acids. On a weight basis, there are twice as many calories in a gram of fat as there are in a gram of carbohydrate.
In summary, fats are an excellent source of energy and the storage of fat is an important process. Furthermore, other kinds of molecules can be converted to fat. You already know that people can get fat from eating sugar. Notice in figure 6.11 that both carbohydrates and fats can enter the Krebs cycle and release energy. Although people require both fats and carbohydrates in their diets, they need not be in precise ratios; the body can make some interconversions. This means that people who eat excessive amounts of carbohydrates will deposit body fat. It also means that people who starve can generate glucose by breaking down fats and using the glycerol to synthesize glucose.

Figure 6.11

PROTEIN RESPIRATION

Proteins can be catabolized and interconverted just as fats and carbohydrates are (review figure 6.11). The first step in using protein for energy is to digest the protein into individual amino acids. Each amino acid then needs to have the amino group (—NH2) removed, a process (deamination) that takes place in the liver. The remaining non-nitrogenous part of the protein is converted to keto acid and enters the respiratory cycle as acetyl, pyruvic acid, or one of the other types of molecules found in the Krebs cycle. As the acids progress through the Krebs cycle, the electrons are removed and sent to the ETS, where their energy is converted into the chemicalbond energy of ATP. The amino group that was removed from the amino acid is converted into ammonia. Some organisms excrete ammonia directly; others convert ammonia into other nitrogen-containing compounds, such as urea or uric acid. All of these molecules are toxic, increase the workload of the liver, can damage the kidneys and other organs, and must be eliminated. They are transported in the blood to the kidneys, where they are eliminated. In the case of a high-protein diet, increasing fluid intake will allow the kidneys to remove the urea or uric acid efficiently.
When proteins are eaten, they are digested into their component amino acids. These amino acids are then available to be used to construct other proteins. Proteins cannot be stored; if they or their component amino acids are not needed immediately, they will be converted into fat or carbohydrates or will be metabolized to provide energy. This presents a problem for individuals who do not have ready access to a continuous source of amino acids in their diet (e.g., individuals on a low-protein diet). If they do not have a source of dietary protein, they must dismantle proteins from important cellular components to supply the amino acids they need. This is why proteins and amino acids are considered an important daily food requirement.
One of the most important concepts is that carbohydrates, fats, and proteins can all be used to provide energy. The fate of any type of nutrient in a cell depends on the cell’s momentary needs. An organism whose daily foodenergy intake exceeds its daily energy expenditure will convert only the necessary amount of food into energy. The excess food will be interconverted according to the enzymes present and the organism’s needs at that time. In fact, glycolysis and the Krebs cycle allow molecules of the three major food types (carbohydrates, fats, and proteins) to be interchanged.
As long as a person’s diet has a certain minimum of each of the three major types of molecules, a cell’s metabolic machinery can manipulate molecules to satisfy its needs. If a person is on a starvation diet, the cells will use stored carbohydrates first. Once the carbohydrates are gone (after about 2 days), the cells will begin to metabolize stored fat. When the fat is gone (after a few days to weeks), the proteins will be used. A person in this condition is likely to die.