Nearly all the vital processes that operate in animals and plants require energy, and all the energy used by animals comes directly or indirectly from plants eaten as food. Plants and many bacteria are able to trap light (or occasionally, chemical energy), using it to convert inorganic materials such as carbon dioxide and water into complex organic products. This energy is “stored” in carbohydrates and lipids and can then be used to do work in the organism, such as chemical work in the biochemical processes, electrical work in nerve cells, or mechanical work in muscles. The amount of energy needed depends on the size and complexity of the organism. But levels of physiological and physical activity are also important—a sleeping person, for example, uses only a small fraction of the energy used when awake and performing strenuous exercise.
Anabolism and catabolism
Metabolism, the name given to the network of biochemical reactions that sustain living processes, consists of constructive (anabolic) and destructive (catabolic) pathways. The breaking down of large molecules into smaller units releases energy that may be used to build other large units. Many thousands of these reactions are going on in the body all the time. The pathways for particular types of molecules, such as proteins or carbohydrates, do not remain separate. They converge so that energy can be released from any available fuel. Similarly, in anabolic processes, a particular compound in excess can be converted to a different material for use in growth or for storage. This flexibility ensures that anabolic and catabolic processes are in balance in a normal organism.
The role of ATP
Adenosine triphosphate (ATP) is a relatively simple compound derived from the purine base adenine. Consisting of adenosine (adenine and the sugar ribose) linked to three phosphate groups, it is the readily accessible energy source used by all plants, animals, and bacteria. The ending phosphate group can be broken off with the release of energy. ATP thus becomes ADP, adenosine diphosphate.
ATP provides energy for immediate use in electrical or mechanical work, for example.
Or it could be energy used to form chemical bonds in new molecules, which may thus store some of the energy released from the ATP. Alternatively, the energy released in other reactions can be used to convert ADP back to ATP. Hence, ATP provides “ready cash” for the organism to spend or save in its “bank account” of carbohydrates and lipids. Energy is also stored in proteins. Protein energy is called upon to some extent during fasting, and it can become the only energy source during starvation, when other resources are exhausted. Some other compounds also contain energy-transferring phosphate bonds, particularly creatine phosphate, which provides an emergency reserve to regenerate ATP rapidly in contracting muscle. In terms of an organism’s total energy output, however, these compounds are of minor importance.
ATP is produced from ADP by a highly complex sequence of reactions that is essentially the same in all organisms. The breakdown of ATP releases energy. So, in order for ADP to form, the same quantity of energy must be input. The energy is produced by the gradual oxidation of molecules. These molecules include hexose sugars and fatty acids, even though these may have been made originally by breaking down other molecules. Eventually, the molecules used to produce ATP are oxidized to carbon dioxide and water, just as they would be if burned directly in air. For this reason, cellular respiration, or breathing, is often referred to as “burning” food. This description is slightly misleading, however. Direct oxidation involves the production of heat energy, which is of limited use to a cell, and an excess of heat energy would be damaging. Instead, cell respiration involves the gradual stripping away of hydrogen atoms from foodstuffs and the controlled transfer of this hydrogen to oxygen. In this way, the production of water is coupled with the release of small “packets” of chemical energy, and the conversion is more controlled than it would be in a single-step reaction. It is also a more efficient source of useful energy.
Hydrogen and electron carriers
A sequence of reactions takes place when ATP is produced. In this sequence, the hydrogen atoms shed by foodstuffs are passed between compounds known as hydrogen carriers. In fact, some of the compounds do not accept hydrogen atoms. They accept only electrons from the hydrogens. This results in the release of hydrogen ions—electrically charged hydrogen atoms. These compounds are called electron carriers—they contain iron or copper atoms that take up or pass on the electrons. Hydrogen and electron carriers first receive two hydrogen atoms or electrons. They then return to their original form by passing the atoms or electrons on to the next carrier.
The first carrier is called nicotinamide adenine dinucleotide (NAD), derived from the vitamin nicotinic acid. NAD accepts hydrogen from foodstuffs, then passes it on to the next carrier. This carrier, a derivative of vitamin B2 (riboflavin) called flavine mononucleotide (FMN), accepts the hydrogen in turn and then passes it on to the next carrier. The final set of carriers is in the enzyme cytochrome oxidase, which transfers electrons to oxygen atoms.
The resulting oxygen ions then combine with hydrogen ions taken up from the medium to form water. This entire respiratory chain, which is built into the structure of certain membranes in the cell, is subdivided into three spans. As two hydrogens or electrons cross each span, the energy released is used to make one molecule of ATP. Thus, the complete oxidation process yields three molecules of ATP.
The first phase in the breakdown of glucose is called glycolysis. In the absence of oxygen, glycolysis is the only method by which most organisms can obtain energy. Glycolysis takes place in the cytoplasm of the cell. (Cytoplasm is the substance in a cell around the nucleus.) This first phase results in the formation of a three-carbon molecule called pyruvic acid. If oxygen is available, the pyruvic acid is moved into the mitochondria, where the next stage occurs. (Mitochondria are sausage-shaped structures in the cytoplasm of cells.) Without oxygen, glycolysis can keep going only if pyruvic acid is continuously converted into lactic acid (in animals) or ethanol (in some other organisms). Lactic acid, the substance that accumulates in muscles, causes fatigue when oxygen is used up during strenuous exercise.
Both lactic acid and ethanol are potentially toxic. They are formed only as a temporary measure until the oxygen is replenished. In contrast, certain bacteria—called anaerobes— use this method as the source of all their energy. For them, oxygen is toxic.
Glycolysis is an inefficient means of converting the energy in glucose into useful packets of ATP energy because there is a net gain of only two ATP’s per glucose molecule used.
The method begins with the input of two ATP’s. The first is used to convert the sugar into glucose. The second is used to form fructose. This is then split into two three-carbon sugar derivatives. These, in turn, are converted to pyruvic acid with the manufacture of four ATPs. Hydrogen atoms are also produced and taken up by NAD. But without oxygen, these hydrogen atoms do not pass along the hydrogen carrier system. The NAD can be regenerated to maintain glycolysis only by transferring the hydrogen to the pyruvic acid, thus forming lactic acid.
Acetyl coenzyme A
Before oxidation can proceed to the second stage, called the Krebs cycle, or citric acid cycle, the pyruvic acid must lose another carbon atom (as carbon dioxide). This reaction produces two hydrogen atoms that pass along the hydrogen-carrier chain and yields three molecules of ATP and one molecule of acetyl coenzyme A (acetyl-CoA). This latter substance is extremely important in the breakdown of carbohydrates and the oxidation of fats and proteins. Acetyl coenzyme is formed by linking the remaining two-carbon molecule of acetic (ethanoic) acid with coenzyme A, a derivative of the B-group vitamin pantothenic acid. Just as the coenzyme NAD may act as a carrier for the transfer of hydrogen atoms, CoA is a carrier for acetyl groups in a number of reactions. An acetyl group is composed of carbon, hydrogen, and oxygen.
Krebs cycle or citric acid cycle
The Krebs cycle, named after the Anglo-German biochemist Hans Krebs who discovered it in 1937, is the final stage in aerobic oxidation, as well as the most significant stage in terms of total energy yield. An equivalent of 12 ATP molecules are formed for each acetyl group oxidized via the cycle. Overall, 38 molecules are formed during the complete oxidation of a single glucose molecule. The oxidation is achieved through aerobic glycolysis and the citric acid cycle. (Aerobic means “in the presence of oxygen.”) This compares with only two ATP units formed in anaerobic glycolysis. (Anaerobic means “without oxygen.”) In this process, a large amount of the total glucose energy remains locked up in the lactic acid or ethanol produced. The citric acid cycle is a highly complex sequence of reactions catalyzed by a number of enzymes, all found within the mitochondria. It begins with the transfer of the acetyl group to the four-carbon oxaloacetic acid molecule. This produces a six-carbon molecule of citric acid.
The citric acid is rearranged to produce isocitric acid. Then, two carbon atoms are sequentially lost (as carbon dioxide) to form first alpha-oxoglutaric acid and then succinic acid. In both these reactions, hydrogen atoms are transferred to the coenzyme NAD. Three ATP molecules are produced as the hydrogen atoms pass down the mitochondrial respiratory chain, as previously described. In the second reaction, a molecule of guanosine triphosphate (GTP) is made. Like ATP, this is an energy-transferring molecule derived from a purine base, guanine. The GTP subsequently transfers its end phosphate to ADP, thus making ATP.
The succinic acid molecule (formed when the citric acid lost two carbon atoms) now loses two hydrogen atoms. This forms fumaric acid and another two ATP molecules. Although no more carbon atoms are lost after succinic acid, two further conversions take place. A water molecule is added to form L-malic acid. Another pair of hydrogen atoms are lost to produce oxaloacetic acid. This leads to the formation of another three ATP molecules. The newly formed oxaloacetic acid is then ready to start the cycle again.
Fatty acid oxidation
Lipids are structural parts of cell membranes and various complex functional compounds (such as hormones). They are stored as droplets of triglycerides (fats) in adipose tissues. These triglycerides are a valuable source of energy. They are particularly important sources for various internal organs such as the heart. They are used in skeletal muscle for prolonged activity such as the flight of migrating birds. Fats are also key energy sources for hibernating mammals—animals that go into a state of deep sleep for an entire season—or part of one.
As in carbohydrate (sugar) oxidation, the final oxidation of fats takes place in the mitochondria. But first the fat must be mobilized. It is broken down by enzymes in the adipose tissue to release free fatty acids. Adipose tissue is connective tissue containing animal fat The fatty acids are then transferred by the blood to the cells of tissue that require energy. In the cells, before entering the mitochondria, the fatty acids are linked with coenzyme A (CoA). The resulting compound then enters the mitochondria via a complex process. This involves the intervention of another molecule—carnitine.
The conversion of fatty acids to CoA derivatives requires the input of energy as ATP, but this investment is soon recovered. The reaction takes place in a repetition of a four-step sequence called beta-oxidation, or the fatty acid spiral. The net result of each sequence in the spiral is removal of the two end carbon atoms on the fatty acid. This leaves the fatty acid two carbons shorter, ready for another sequence in the spiral. The fatty acid then joins the citric acid cycle. The process is repeated until the final fragment left is acetyl-CoA. In each sequence of the fatty acid spiral, four hydrogen atoms are removed. Oxidation of the fatty acid yields five molecules of ATP.
The process is varied slightly if the acid contains an odd number of carbon atoms or is partly unsaturated (containing carbon-carbon double bonds). But in all cases, it is a very good energy source. Not only are five ATP molecules produced for each two-carbon fragment, but each fragment is itself oxidized to form 12 more ATPs. For example, in the breakdown of the 16-carbon palmitic acid, a total of 129 ATP molecules are produced.
The adaptability of the oxidation pathways described earlier is especially important in the breakdown of the third energy source—protein. The structures of the amino acids making up the protein vary to the extent that the preliminary pathway for each amino acid is different. Some are converted into a compound called acetyl-CoA. Others are converted into intermediates that join at later stages of the citric acid cycle. In each case, the amino group on the amino acid has to be removed first In normal circumstances, protein plays a minor role in total energy production. Except during starvation, it provides (mainly after conversion to glucose) only 10 per cent of the body’s needs.
Amino acid degradation and the urea cycle
As well as being oxidized occasionally to produce energy, amino acids are also broken down during the normal turnover of protein in the tissues. If the amino acid unit is not needed in forming new protein, it is oxidized. Excess amounts of amino acids absorbed in food are also oxidized. The amino group removed at the start of amino acid oxidation has to be expelled from the body because it contains ammonia, a toxic substance. An intermediate in the citric acid cycle accepts the amino group and then releases it as an ammonium ion. Another intermediate also readily accepts amino groups, forming aspartate, which plays an important part in nitrogen elimination. Nitrogen, the main constituent of ammonia, has to be converted to a form in which it can be passed out of the body in small volumes of water. This compound is urea. The urea cycle pathway in which it is made occurs in most land animals. Fish and some other aquatic animals excrete ammonia directly because they have plenty of water available and are not likely to dehydrate. Before entering the cycle, the ammonia reacts with bicarbonate and ATP to form carbamoyl phosphate. This then reacts with ornithine to produce citrulline. This compound combines with aspartic acid to form arginosuccinic acid. In the next stage, this acid breaks down into the by-product fumaric acid and arginine. Finally, arginine breaks down to ornithine (for reuse in the cycle) and urea.
Photosynthesis is the method used by plants (and ultimately animals) to get the energy they need for their metabolic processes. Light energy is used to synthesize (produce) organic molecules from water and carbon dioxide. In some ways, it is therefore a reverse of the process of respiration. It takes place in organelles—specialized parts of a plant cell-called chloroplasts. Chloroplasts are structurally and functionally analogous to mitochondria. They are thought to have originated from blue-green algae in the sea; mitochondria from aerobic bacteria on land. Mitochondria, however, are found in all organisms, while chloroplasts occur only in green algae and higher plants. Certain bacteria and the blue-green algae also photosynthesize, but the process takes place in structures that are simpler than chloroplasts. Enormous amounts of light energy are absorbed by plants each year during photosynthesis. Much of this occurs in marine algae.
The light reaction
Photosynthesis occurs in two stages. The first stage requires the presence of light, whereas the second can take place in darkness. The light reaction is dependent on the green plant pigment chlorophyll. This is a porphyrin compound containing magnesium. It is related to hemoglobin. There are several similar pigments in chlorophyll. Only the blue-green chlorophyll (a) is common to all plants. Most plants also contain yellow-green chlorophyll (b), xanthophyll (yellow), carotene (orange and pheophytin. Pheophytin, a gray pigment, is probably a breakdown product of chlorophyll. Each pigment absorbs light of slightly different wavelengths. The purpose of the light reaction is to release hydrogen from water. The hydrogen reduces carbon dioxide to carbohydrates in structures called thylakoids, which resemble stacked plates. All the later reactions occur in the liquid, or stroma, of the chloroplast There are two types of light centers in thy-lakoid membranes. These centers are called photosystems I and II. Absorption of light of a particular wavelength by pigment at center II excites the molecule in center I. Electrons are released. This process reduces (combines with hydrogen) a benzene compound called quinone on the other side of the membrane. The electrons are replaced from water molecules. This process releases oxygen gas and hydrogen ions. Absorption of light at another wavelength by chlorophyll at center I also results in electron release. This time, a phosphate (NADP) is reduced. Both quinone and the phosphate are hydrogen carriers. Their reduction by electrons produced in the light reactions also requires the uptake of hydrogen ions. A compound of quinone and hydrogen is then reoxidized by a sequence of carriers (including cytochromes). Electrons are eventually transferred to replace those ejected from center I. Hydrogen ions are released inside the thylakoid. The net effect of the two photosystems is that the phosphate is reduced; water is split; oxygen is released; and hydrogen ions are separated across the membrane. These ions then return. A special enzyme is used to conserve the energy released bv this process as ATP. This is the same principle that underlies ATP production by mitochondria.
The dark reaction
The dark reaction begins with the combination of a carbon dioxide molecule with a five-carbon sugar. This splits to form two further molecules of a glyceric acid. The acid is then reduced by the hydrogen carried by a phosphate compound. This forms a three-carbon triose phosphate, which can be used to build up the hexose sugars that are later stored as starch.
But not all the triose phosphate goes to make sugars. Some has to be used in re-forming a type of phosphate. By doing so, carbon dioxide continues to be taken up by a pathway known as the Calvin cycle. Some of the steps of this cycle—including the reduction of phos-phoglyceric acid—require ATP. This is available as a result of the light reactions. Studies with radioactive carbon have shown that phos-phoglyceric acid is also vital in building up amino acids and fats.