exam 3: chapter 7,8,10,11

METABOLIC PATHWAYS CONSIST OF LINKED CHEMICAL REACTIONS

A metabolic pathway consists of a series of interrelated, enzyme-catalyzed chemical reactions. Some metabolic pathways are simple, consisting of 3 to 4 chemical reactions, whereas others are more complex, with 10 to 15 chemical reactions. Chemical reactions transform molecules, sometimes breaking them down and at other times forming new ones. A molecule that enters a chemical reaction is a substrate, also called a reactant, and the resulting molecule is a product. A chemical reaction can be expressed as an equation with the substrate(s) written on the left of an arrow that points to the product(s): A 1 B → C 1 D. In this example, A and B are substrates, and C and D are products. The arrow means "yields." As shown in Figure 7.1, the product of one chemical reaction in a pathway becomes the substrate in the reaction that follows. Products formed before a metabolic pathway reaches completion are called intermediate products, whereas the final product(s) in a pathway is/are the end product(s). It is common for intermediate products and end product(s) of one metabolic pathway to enter other metabolic pathways.

HIGH-ENERGY BONDS ENABLE ATP TO STORE AND RELEASE ENERGY

As illustrated in Figure 7.5, a molecule of ATP consists of three basic units: the sugar ribose, a base called adenine, and three phosphate groups (hence, ATP is a triphosphate). Together, ribose and adenine are referred to as adenosine. Of particular importance is the energy contained in the chemical bonds holding the phosphate groups together. These high-energy bonds enable ATP to both store and release energy. When cells need energy, a phosphate group is broken off of ATP, releasing energy and inorganic phosphate (symbolized as Pi). This results in the formation of adenosine diphosphate (ADP). The energy released when a phosphate bond is split from ATP is used to drive metabolic reactions. ATP is then regenerated by the addition of a phosphate group to ADP.

ATP IS SYNTHESIZED BY SUBSTRATE PHOSPHORYLATION AND BY OXIDATIVE PHOSPHORYLATION

Because ATP is not stored to any extent in the body, it is important for cells to be able to make ATP as it is needed. In fact, cells use ATP almost as quickly as it is made. ATP can be synthesized in two ways—substrate phosphorylation and oxidative phosphorylation. Because substrate phosphorylation does not require oxygen, this process is particularly important when tissues have little oxygen available to them. Although all cells have the capability to carry out substrate phosphorylation, the process produces relatively little ATP. Instead, most ATP is synthesized via oxidative phosphorylation. Because the energy contained within energy-yielding nutrients cannot be transferred directly to ADP, electrons (e2) and hydrogen ions (H1) are transferred to the oxidized coenzymes NAD1 and FAD. Once reduced, these coenzymes (NADH 1 H1 and FADH2) can be reoxidized back to NAD1 and FAD. This process releases energy and is accomplished by a series of chemical reactions that link the oxidation of NADH 1 H1 and FADH2 to the synthesis of ATP. The process whereby NADH 1 H1 and FADH2 are oxidized and ADP is phosphorylated is called oxidative phosphorylation. These reactions are coupled, because the energy needed to phosphorylate ADP is provided by the oxidation of NADH 1 H1 and FADH2. In this way, the energy contained in the reduced coenzymes is used to form ATP.

What Is the Role of ATP in Energy Metabolism?

Cells are unable to use nutrients directly for energy. That is, the energy stored in the chemical bonds of nutrients must first be converted into a form that cells can use—namely adenosine triphosphate (ATP). When catabolized, approximately half of the energy contained in energy-yielding nutrients is used to generate ATP; the rest is lost as heat. By comparison, an automobile engine captures only about 10 to 20% of the energy in gasoline when it is combusted. ATP is uniquely suited to transfer the energy contained in its chemical bonds to chemical reactions that require energy. In this way, ATP provides the energy needed for protein synthesis, muscle contraction, active transport, nerve transmission, and all other energy-requiring reactions that take place in the body

ENERGY METABOLISM IS REGULATED BY CHANGES IN ATP LEVELS

Energy metabolism can be thought of as an elaborate molecular highway system made up of anabolic and catabolic pathways. Whereas the anabolic pathways are involved in the synthesis of molecules that store energy, the catabolic pathways are involved in the breakdown of those molecules to release energy. The pathway or combination of pathways used by the body at any given time depends primarily on the cellular need for energy. When ATP is readily available, the activity of energy-yielding catabolic pathways decreases, and the activity of energy-storing anabolic pathways increases. Conversely, low ATP availability increases energy-yielding catabolic activity and decreases energy-storing anabolic activity. In simple terms, anabolic (synthesis) and catabolic (breakdown) pathways work hand in hand to ensure that the energy (ATP) needs of cells are met.

How Do Catabolic Pathways Release Stored Energy?

Energy-yielding nutrients such as glucose, fatty acids, and amino acids store energy in their chemical bonds. For cells to produce ATP, these nutrients must undergo a series of chemical reactions that make up catabolic pathways. These pathways are interrelated in such a way that intermediate products or end products of one pathway often become substrates for other pathways. At first glance, the many catabolic pathways can appear overwhelming. However, they can be simplified by grouping them into four stages, as illustrated in Figure 7.7. Stage 1: The first stage of catabolism breaks down complex molecules into their fundamental building blocks. That is, protein to amino acids, glycogen to glucose, and triglycerides to fatty acids and glycerol molecules. These metabolic pathways are proteolysis, glycogenolysis, and lipolysis, respectively. Notice that each of these metabolic processes (proteolysis, glycogenolysis, and lipolysis) all have the same ending—lysis. Lysis means separation or breaking apart, which is exactly what is happening here Stage 2: During the second stage, the basic building blocks (amino acids, glucose, fatty acids, and glycerol) enter specific pathways whereby each is converted into an intermediate product that can enter a common pathway called the citric acid cycle—the third stage of catabolism Stage 3: The third stage of catabolism begins when intermediate products formed during Stage 2 enter the citric acid cycle and are broken down further to form carbon dioxide, releasing energy in the process. Much of the energy released during Stage 3 is transferred to the coenzymes NAD1 and FAD, forming NADH 1 H1 and FADH2, respectively. In addition, small amounts of ATP are formed via substrate phosphorylation Stage 4: The fourth and final stage of catabolism begins when NADH 1 H1 and FADH2 enter the electron transport chain. It is here where most ATP production occurs via oxidative phosphorylation

CHEMICAL REACTIONS REQUIRE ENZYMES

For a chemical reaction to occur, reacting molecules (substrates) must make contact with each other and then be chemically transformed into one or more products. Because these reactions are not likely to occur on their own, the body relies on catalysts to speed them up. In cells, biological catalysts are proteins called enzymes. If it were not for enzymes, metabolic reactions would occur very slowly, if at all. Although enzymes increase the rate at which chemical reactions occur, they themselves do not undergo change. The names of most enzymes end in -ase, such as the names of the digestive enzymes sucrase, maltase, and lactase, but there are exceptions. When scientists first discovered that enzymes were proteins, enzymes were often given names ending in -in. The names of the enzymes pepsin, trypsin, and chymotrypsin—needed for protein digestion—reflect this older practice. Enzymes can be classified according to the type of chemical reaction they catalyze. For example, enzymes that catalyze hydrolysis reactions are called hydrolases. Similarly, enzymes that transfer a chemical group from one molecule to another are categorized as transferases. Substrates attach to a special surface on the enzyme called the active site, forming an enzyme-substrate complex. Researchers previously thought that the shape of the active site was complementary to the shape of the substrate—like the pieces of a jigsaw puzzle. It was later realized that this was not the case, and that the shape of the active site changes to fit the shape of the substrate. The active site wraps around the substrate, altering its chemical structure and transforming it into the product. The product is released from the active site, and the enzyme is then free to bind yet another substrate (Figure 7.3). Enzymes have specificity, meaning that each interacts with only certain substrates. Because of this specificity, the body makes thousands of different enzymes to catalyze thousands of different reactions.

CATABOLIC PATHWAYS METABOLIZE GLUCOSE FOR ENERGY

Glucose is a rich source of energy that can be used by all cells in the body to produce ATP by means of catabolic energy pathways. Most glucose in the body comes from carbohydrate-rich foods. However, when additional glucose is needed, the hormone glucagon stimulates the breakdown of glycogen in the liver and the release of glucose into the blood. This metabolic process, called glycogenolysis, results in the breakdown of glycogen to glucose and takes place in Stage 1 of carbohydrate catabolism. The hormones epinephrine and cortisol also stimulate glycogenolysis in skeletal muscle.

Hormones Also Regulate Energy Metabolism

Hormones are important regulators of energy metabolism, helping the body shift between anabolic and catabolic pathways. Endocrine tissues can detect changes in substrate availability and respond by secreting appropriate hormones. These hormones then suppress or activate key enzymes in metabolic pathways. As a result, metabolic pathways can be "switched" on or off. The primary hormones involved in the regulation of catabolic and anabolic pathways are insulin, glucagon, cortisol, and epinephrine. As you learned in Chapter 4, insulin is an anabolic hormone that promotes energy storage in the forms of glycogen, triglyceride, and protein. To do this, insulin increases the activity of anabolic pathways and decreases the activity of catabolic pathways. When energy availability is limited, the pancreatic hormone glucagon promotes catabolic pathways and inhibits anabolic pathways. In this way, glucagon increases energy availability by mobilizing energy-yielding molecules that have been "stored for a rainy day." During times of stress and starvation, cortisol and epinephrine, hormones released from the adrenal glands, also play important roles in directing energy metabolism. These hormones stimulate catabolic pathways that help increase fuel availability. For example, cortisol and epinephrine stimulate the breakdown of glycogen stored in muscles to increase glucose availability. The energy in the food we eat must ultimately be converted to ATP before cells can use it to perform the functions that sustain life. Next, you will learn how this is accomplished.

Inherited Metabolic Diseases

Metabolic disorders that result from genetic defects are called inherited metabolic diseases (also called inborn errors of metabolism). These genetic abnormalities are caused by a deficiency in or absence of one or more enzymes needed for a metabolic pathway to function properly (Figure 7.2). As a result, the altered metabolic pathway can produce harmful substances that interfere with normal physiologic functions. Problems can also arise when the metabolic pathway is unable to produce essential compounds and when substrates that are normally broken down accumulate in the blood. The number of inherited metabolic diseases is enormous, each with a wide range of effects. Because some inherited metabolic diseases can result in serious health problems and even death, a variety of newborn screening tests are routinely administered in hospitals across the United States. Early detection can mean early treatment, which often can prevent serious complications from occurring. In fact, some inherited metabolic diseases can be effectively managed by the elimination or restriction of certain dietary components. This is certainly the case for a condition called phenylketonuria (PKU). People with PKU lack the enzyme phenylalanine hydroxylase, which converts the essential amino acid phenylalanine to the nonessential amino acid tyrosine. If untreated, PKU results in dangerously high circulating levels of phenylalanine as well as insufficient levels of tyrosine. Because this can cause serious health problems, including brain damage, most babies in the United States are tested for PKU shortly after birth. An infant found to have PKU is fed a special formula containing minimal amounts of phenylalanine and adequate amounts of tyrosine.

METABOLIC PATHWAYS CAN BE CATABOLIC OR ANABOLIC

Metabolic pathways can be catabolic or anabolic. Catabolic pathways (catabolism) release energy through the breakdown of complex molecules into simpler ones, whereas anabolic pathways (anabolism) require energy (ATP) to construct complex molecules from simpler ones. The energy made available by catabolic reactions often drives anabolic reactions. Likewise, the products of catabolic pathways provide many of the building blocks needed for anabolic pathways. Metabolic pathways that can be used for both catabolism and anabolism are called amphibolic pathways. The availability of metabolic fuels (glucose, fatty acids, and amino acids) fluctuates throughout the day. After a meal, these energy sources are readily available and tend to exceed the body's immediate energy needs. During this time, anabolic pathways favor the storage of excess glucose, amino acids, and fatty acids as glycogen, protein, and triglycerides, respectively. Conversely, catabolic pathways increase fuel availability by breaking down the body's stored energy reserves—glycogen, protein, and triglycerides—into glucose, amino acids, and fatty acids, respectively. In this way, the body shifts between anabolic to catabolic pathways in response to energy availability and need. The major anabolic and catabolic pathways involved in energy metabolism are reviewed in Table 7.1.

what is energy metabolism

Metabolism is defined as the sum of all chemical reactions that take place in the body. The term energy metabolism refers to hundreds of chemical reactions involved in the breakdown, synthesis, and transformation of the energy-yielding nutrients—glucose, amino acids, and fatty acids—that enable the body to store and use energy. In addition to these nutrients, cells can also metabolize alcohol for a source of energy, as you will learn in the Nutrition Matters following this chapter. Metabolic pathways work together in a complex way to maintain a steady supply of energy in the form of adenosine triphosphate (ATP), the high-energy molecule used to fuel cellular activities. These pathways occur simultaneously and are highly coordinated, allowing the body to use different combinations of nutrients in response to various physiological states. This versatility helps ensure that raw materials and energy are available to cells at all times.

Oxidative Phosphorylation Generates the Majority of ATP

Oxidative phosphorylation accounts for approximately 90% of ATP production and involves a series of linked chemical reactions that make up the electron transport chain (Figure 7.6). The electron transport chain (also called the electron transport system) is located in the inner membrane of the mitochondria. This convoluted membrane divides the inside of the mitochondrion into inner and outer compartments. The inner compartment is also referred to as the mitochondrial matrix. The space situated between the inner and outer mitochondrial membranes is called the intermembrane space (recall that inter means between).The electron transport chain consists of a series of protein complexes that are embedded in the inner mitochondrial membrane. When NADH 1 H1 and FADH2 enter the electron transport chain, enzymes remove their electrons (e2) and hydrogen ions (H1), regenerating NAD1 and FAD (Figure 7.6, step 1). The released electrons (e2) and hydrogen ions (H1) take separate routes. The electrons (e2) pass along the protein complexes, much like water in a bucket brigade. This movement releases energy that is used to pump the hydrogen ions (H1) out of the mitochondrial matrix and into the intermembrane space (Figure 7.6, step 2). The accumulation of hydrogen ions in the intermembrane space creates a powerful force. When this force gains sufficient strength, the hydrogen ions re-enter the mitochondrial matrix by passing through narrow channels— somewhat like tunnels (Figure 7.6, step 3). The movement of hydrogen ions through these channels releases energy that is used by the enzyme ATP synthase to attach a phosphate group to ADP. Thus, ATP is produced (Figure 7.6, step 4). Because NADH 1 H1 and FADH2 enter the electron transport chain at different locations along the protein complexes, the amount of ATP generated by these coenzymes differs. Nonetheless, the ATP yield is approximately three ATPs and two ATPs for each NADH 1 H1 and FADH2, respectively.† At the completion of the electron transport chain, a group of iron- containing protein complexes called cytochromes reunites the electrons (e2) and hydrogen ions (H1) to form hydrogen (Figure 7.6, step 5). The hydrogen molecules then combine with oxygen (O2 ) to form water (H2O). This is why the electron transport chain and its accompanying oxidative phosphorylation reaction are considered aerobic (oxygen-requiring) metabolic processes. In summary, cellular metabolic pathways convert the energy contained in NADH 1 H1 and FADH2 to usable energy in the form of ATP. But where do the NADH 1 H1 and FADH2 come from? As you will learn next, the answer lies in the breakdown of macronutrients.

Coenzymes and Energy Transfer Reactions

Recall from Chapter 3 that reduction- oxidation (redox) reactions involve the gain and loss of electrons. Specifically, oxidation is the loss of electrons, whereas reduction is the gain of electrons. These reactions often occur simultaneously and are referred to as coupled reactions. In other words, when one molecule is oxidized (loss of electrons and hydrogen ions), another is reduced (gain of electrons and hydrogen ions) Coupled redox reactions allow energy to be transferred from one molecule to another. Many coenzymes exist in two forms—oxidized (NAD1, FAD, and NADP1) and reduced (NADH 1 H1, FADH2, and NADPH 1 H1). When energy-rich molecules are oxidized, their electrons and hydrogen ions are transferred to NAD1 and FAD. The coenzyme NAD1 can accept two electrons (2 e2) and two hydrogen ions (2 H1), forming NADH 1 H1.* Similarly, FADH2 is formed when two electrons (2 e2) and two hydrogen ions (2 H1) are transferred to FAD. The energy carried by these reduced coenzymes (NADH 1 H1 and FADH2) is used to produce the body's most important energy source—adenosine triphosphate (ATP). The oxidation and reduction of coenzymes are illustrated in Figure 7.4. The reduced form of the coenzyme NADPH 1 H1 also plays an important role in energy-requiring anabolic pathways. Specifically, NADPH 1 H1 is needed for the synthesis of new compounds in the body such as fatty acids, cholesterol, DNA, and RNA. NADPH 1 H1 is transformed to NADP1 when it releases two electrons (2 e2) and two hydrogen ions (2 H1).

Cofactors and Coenzymes Assist Enzymes

Some enzymes require assistance to carry out their catalytic functions. These enzyme "helpers" are called cofactors and coenzymes. Cofactors are inorganic substances such as zinc, potassium, iron, and magnesium. In order to function, some enzymes require cofactors to be attached to their active site. Coenzymes are organic molecules, some of which are derived from vitamins such as niacin and riboflavin. Examples of coenzymes include nicotinamide adenine dinucleotide (NAD1), flavin adenine dinucleotide (FAD), and nicotinamide adenine dinucleotide phosphate (NADP1). Unlike cofactors, coenzymes are not actually a part of the enzyme structure. Rather, they assist enzymes by accepting and donating hydrogen ions (H1), electrons (e2), and other molecules during chemical reactions. This is why, while vitamins and minerals themselves do not provide cells with a source of energy (ATP), they play a critical role in energy metabolism by acting as cofactors and coenzymes.

Glycolysis Splits Glucose into Subunits

The word glycolysis literally means the "splitting of sugar," which is what happens in Stage 2 of carbohydrate metabolism. Glycolysis is a chemical pathway that ultimately splits the six-carbon glucose molecule into two three-carbon subunits called pyruvate. These reactions occur in the cytoplasm of cells. Because oxygen is not required, glycolysis is an anaerobic metabolic pathway. As you can see from Figure 7.8, glycolysis yields small amounts of energy— two ATPs and two molecules of NADH 1 H1 per glucose. However, this represents only a small amount of the total energy available in each glucose of acetyl-CoA from pyruvate also results in production of carbon dioxide and NADH 1 H1. Under aerobic conditions, acetyl-CoA is now ready to enter Stage 3 of carbohydrate catabolism—the citric acid cycle.