Energy is the ability to do work. Cells use oxygen to trans- form the breakdown products of the foods we eat into the energy needed for muscle contraction; the transport of ions and other molecules across cell membranes; and the synthesis of enzymes, hormones, and other macromolecules. Energy metabolism refers to the processes by which fats, proteins, and carbohydrates from the foods we eat are converted into energy or complex energy sources in the cell. Catabolism and anabolism are the two phases of metabolism. Catabolism consists of breaking down stored nutrients and body tissues to produce energy. Anabolism is a constructive process in which more complex molecules are formed from simpler ones.
The special carrier for cellular energy is ATP. ATP molecules consist of adenosine, a nitrogenous base; ribose, a five-carbon sugar; and three phosphate groups (Fig. 4.13). The phosphate groups are attached by two high-energy bonds. Large amounts of free energy are released when ATP is hydrolyzed to form adenosine diphosphate (ADP), an adenosine molecule that contains two phosphate groups. The free energy liberated from the hydrolysis of ATP is used to drive reactions that require free energy. Energy from foodstuffs is used to convert ADP back to ATP. Because energy can be “saved or spent” using ATP, ATP is often called the energy currency of the cell.
Energy transformation takes place within the cell through two types of energy production— the anaerobic (i.e., without oxygen) glycolytic pathway, occurring in the cytoplasm, and the aerobic (i.e., with oxygen) pathway, occurring in the mitochondria. The anaerobic glycolytic pathway serves as an important prelude to the aerobic pathway. Both pathways involve oxidation–reduction reactions involving an electron donor, which is oxidized in the reaction, and an electron acceptor, which is reduced in the reaction. In energy metabolism, the breakdown products of carbohydrate, fat, and protein metabolism donate electrons and are oxidized, and the coenzymes nicotinamide adenine dinucleotide (NAD+) and flavin adenine dinucleotide (FAD) accept electrons and are reduced.
Glycolysis is the process by which energy is liberated from glucose. It is an important energy provider for cells that lack mitochondria, the cell organelle in which aerobic metabolism occurs. This process also provides energy in situations when delivery of oxygen to the cell is delayed or impaired. Glycolysis involves a sequence of reactions that convert glucose to pyruvate, with the concomitant production of ATP from ADP. The net gain of energy from the glycolysis of one molecule of glucose is two ATP molecules. Although comparatively inefficient as to energy yield, the glycolytic pathway is important during periods of decreased oxygen delivery, as occurs in skeletal muscle during the first few minutes of exercise.
Glycolysis requires the presence of NAD+. Important end products of glycolysis are pyruvate and NADH (the reduced form of NAD+) plus H+. When oxygen is present, pyruvate moves into the aerobic mitochondrial pathway, and NADH + H+ delivers its electron and proton (H+) to the oxi-dative electron transport system. Transfer of electrons from NADH + H+ to the electron transport system allows the glycolytic process to continue by facilitating the regeneration of NAD+. Under anaerobic conditions, such as cardiac arrest or circulatory shock, pyruvate is converted to lactic acid, which diffuses out of the cells into the extracellular fluid. Conversion of pyruvate to lactic acid is reversible, and after the oxygen supply has been restored, lactic acid is converted back to pyruvate and used directly for energy or to synthesize glucose.
Much of the conversion of lactic acid occurs in the liver, but a small amount can occur in other tissues. The liver removes lactic acid from the bloodstream and converts it to glucose in a process called gluconeogenesis. This glucose is released into the bloodstream to be used again by the muscles or by the central nervous system (CNS). Heart muscle is also efficient in converting lactic acid to pyruvic acid and then using the pyruvic acid for fuel. Pyruvic acid is a particularly important source of fuel for the heart during heavy exercise when the skeletal muscles are producing large amounts of lactic acid and releasing it into the bloodstream.
Aerobic metabolism occurs in the cell’s mitochondria and involves the citric acid cycle and the electron transport chain. It is here that the carbon compounds from the fats, proteins, and carbohydrates in our diet are broken down and their electrons combined with molecular oxygen to form carbon dioxide and water as energy is released. Unlike lactic acid, which is an end product of anaerobic metabolism, carbon dioxide and water are generally harmless and easily eliminated from the body. In a 24-hour period, oxidative metabolism produces 300 to 500 mL of water.
The citric acid cycle, sometimes called the tricarboxylic acid (TCA) or Krebs cycle, provides the final common path- way for the metabolism of nutrients. In the citric acid cycle, which takes place in the matrix of the mitochondria, an activated two-carbon molecule of acetyl-coenzyme A (acetyl- CoA) condenses with a four-carbon molecule of oxaloacetic acid and moves through a series of enzyme-mediated steps. This process produces hydrogen atoms and carbon dioxide. As hydrogen is generated, it combines with NAD+ or FAD for transfer to the electron transport system. In the citric acid cycle, each of the two pyruvate molecules formed in the cytoplasm from one molecule of glucose yields another molecule of ATP along with two molecules of carbon dioxide and eight electrons that end up in three molecules of NADH + H+ and one of FADH2 . Besides pyruvate from the glycolysis of glucose, products of amino acid and fatty acid degradation enter the citric acid cycle and contribute to the generation of ATP
Oxidative metabolism, which supplies 90% of the body’s energy needs, takes place in the electron transport chain in the mitochondria. The electron transport chain oxidizes NADH + H+ and FADH and donates the electrons to oxygen, which is reduced to water. Energy from reduction of oxygen is used for phosphorylation of ADP to ATP. Because the formation of ATP involves the addition of a high-energy phosphate bond to ADP, the process is sometimes called oxidative phosphorylation. Among the members of the electron transport chain are several iron-containing molecules called cytochromes. Each cytochrome is a protein that contains a heme structure similar to that of hemoglobin. The last cytochrome complex is cytochrome oxidase, which passes electrons from cytochrome c to oxygen. Cytochrome oxidase has a lower binding affinity for oxygen than myoglobin (the intracellular heme-containing oxygen carrier) or hemoglobin (the heme-containing oxygen transporter in erythrocytes in the blood). Thus, oxygen is pulled from erythrocytes to myoglobin and from myoglobin to cytochrome oxidase, where it is reduced to H2O. Although iron-deficiency anemia is characterized by decreased levels of hemoglobin, the iron-containing cytochromes in the electron transport chain in tissues such as skeletal muscle are affected as well. Thus, the fatigue that develops in iron-deficiency anemia results, in part, from impaired function of the electron transport chain.