Joanne Willey, Kathleen Sandman, Dorothy Wood, Prescott's Microbiology PDF

232 CHAPTER 11 | Catabolism: Energy Release and Conservation Proteins Polysaccharides Phospholipids Glucose Glycolytic...

232 CHAPTER 11 | Catabolism: Energy Release and Conservation Proteins Polysaccharides Phospholipids Glucose Glycolytic reactions Hexokinase Glucose 6-phosphatase Gluconeogenic Glucose 6-phosphate reactions Amino acids Monosaccharides Glycer ol + Fatty acids Freely reversible reactions Glycolytic Fructose 6-phosphate pathways ATP NADH NADH FADH 2 Phospho- Fructose 1,6-bisphosphatase NH3 fructokinase Pyruvate Fructose 1,6-bisphosphate NADH Acetyl-CoA Oxaloacetate Citrate ATP NADH FADH 2 Isocitrate Tricarboxylic acid cycle Phosphoenolpyruvate (PEP) CO 2 Pyruvate PEP carboxykinase α-Ketoglutarate kinase Pyruvate carboxylase Succinyl-CoA CO 2 Pyruvate Figure 11.4 The Embden-­Meyerhof Pathway Is an Example Figure 11.3 Pathways Used by Chemoorganotrophs to Catabolize ­Organic of an Amphibolic Pathway. Many reactions of this pathway are Energy Sources. Notice that these pathways funnel metabolites into the glycolytic catalyzed by enzymes that function in glycolysis and in an anabolic pathways and the tricarboxylic acid cycle, thus increasing metabolic efficiency and pathway called gluconeogenesis. Gluconeogenesis reverses the flexibility. glycolytic process and allows cells to synthesize glucose from smaller molecules such as pyruvate. Note that some glycolytic reactions are catalyzed by enzymes unique to that pathway. ­Likewise, some gluconeogenic reactions are catalyzed by enzymes unique to Because a carbon source can function as an energy source or gluconeogenesis. Therefore, although they share some enzymes, the for anabolic purposes, some pathways include enzymes that two pathways are distinct. function both catabolically and anabolically. These are called MICRO INQUIRY Is NAD+ reduced to NADH in the catabolic or amphibolic pathways (Greek amphi, on both sides). For in- anabolic direction of this pathway? stance, many of the enzymes of the Embden-Meyerhof pathway (a glycolytic pathway) are freely reversible. They function cata- bolically during glycolysis but anabolically during gluconeo- genesis, a pathway that generates glucose from pyruvate and widely used by microbes and has important practical applications, other small molecules (figure 11.4). Other reactions in glycolysis including the production of many foods. Microbiology of are not reversible. During glycolysis, an enzyme catalyzes the fermented foods: beer, cheese, and much more (section 41.5) reaction in a catabolic direction, and during gluconeogenesis, a different enzyme catalyzes the reverse, anabolic reaction. Thus, glycolysis and gluconeogenesis are two distinct pathways. Comprehension Check Our discussion of chemoorganotrophy begins with aerobic 1. Give examples of the types of electron acceptors used by respiration and introduces the glycolytic pathways, TCA cycle, and fermentation and respiration. What is the difference between aerobic other important processes. Many of these also occur during an- respiration and anaerobic respiration? aerobic respiration. Fermentation is quite distinct from respiration. 2. Why is it to a cell’s advantage to catabolize diverse organic energy It involves only a subset of the reactions that function during respira- sources by funneling them into a few common pathways? tion and only partially catabolizes the energy source. However, it is 3. What are amphibolic pathways? Why are they important? wil11886_ch11_228-264.indd 232 23/10/18 10:08 am  11.4 Glucose to Pyruvate: The First Step 233 glyco, sweet; lysis, a loosening). However, in some texts, the term 11.3 Aerobic Respiration glycolysis refers only to the Embden-Meyerhof pathway. For the sake of simplicity, the detailed structures of some metabolic in- Can Be Divided into Three Steps termediates are not used in pathway diagrams. However, these After reading this section, you should be able to: can be found in appendix II. a. Describe in general terms what happens to a molecule of glucose during aerobic respiration Embden-Meyerhof Pathway: b. List the end products made during aerobic respiration The Most Common Route to Pyruvate c. Identify the process that generates the most ATP during aerobic The Embden-Meyerhof pathway is undoubtedly the most com- respiration mon pathway for glucose degradation to pyruvate. It is found in all major groups of microorganisms, as well as in plants and ani- Aerobic respiration is a process that can completely catabolize a mals, and functions in the presence or absence of O2. It provides reduced organic energy source to CO2 using the glycolytic path- several precursor metabolites, NADH, and ATP for the cell. ways and TCA cycle with O2 as the terminal electron acceptor for The pathway is divided into two parts: a 6-carbon phase and a an electron transport chain (figure 11.2). The catabolism of glu- 3-carbon phase (figure 11.5 and appendix II). In the initial 6-carbon cose can be divided into three steps. It begins with the formation phase, ATP is used in two phosphorylation reactions, yielding of pyruvate, using one or more pathways described in section 11.4. fructose 1,6-bisphosphate. This preliminary phase “primes the These pathways also produce NADH, FADH2, or both. Next pyru- pump” by adding phosphates to each end of the sugar. In essence, vate is fed into the TCA cycle and oxidized completely to CO2 with the organism invests some of its ATP so that more can be made the production of some GTP or ATP, NADH, and FADH2 (section later in the pathway. 11.5). Finally, the NADH and FADH2 formed by glycolysis and the The 3-carbon, energy-conserving phase begins when TCA cycle are oxidized by an electron transport chain, using O2 as fructose 1,6-bisphosphate is cleaved into two 3-C molecules: the terminal electron acceptor (section 11.6). It is the activity of the dihydroxyacetone phosphate and glyceraldehyde 3-phosphate. electron transport chain that conserves most of the energy used to Dihydroxyacetone phosphate is immediately converted to make ATP during aerobic respiration. glyceraldehyde 3-phosphate. Thus two molecules of glyceral- dehyde 3-phosphate are formed from a single glucose by the cleavage reaction. These are then catabolized to pyruvate in a 11.4 Glucose to Pyruvate: The First Step five-step process. In contrast to the 6-carbon phase when ATP is consumed, in After reading this section, you should be able to: the 3-carbon phase of the pathway NADH and ATP are produced. a. List the three major pathways that catabolize glucose to pyruvate NADH is formed when glyceraldehyde 3-phosphate is oxidized b. Describe substrate-level phosphorylation with NAD+ as the electron acceptor, and a phosphate is simulta- neously incorporated to give a high-energy molecule called c. Diagram the major changes made to glucose as it is catabolized by the Embden-Meyerhof, Entner-Doudoroff, and pentose phosphate 1,3-bisphosphoglycerate. This reaction sets the stage for ATP pathways production. The phosphate on the first carbon of 1,3-bisphospho- d. Identify those reactions of the Embden-Meyerhof, Entner-Doudoroff, glycerate is donated to ADP to produce ATP. This is an example and pentose phosphate pathways that consume ATP, produce ATP and of substrate-level phosphorylation because ADP phosphoryla- NAD(P)H, generate precursor metabolites, or are redox reactions tion is coupled with the exergonic hydrolysis of a high-energy e. Calculate the yields of ATP and NAD(P)H by the Embden-Meyerhof, molecule having a higher phosphate transfer potential than ATP Entner-Doudoroff, and pentose phosphate pathways (see table 10.1). A second ATP is made by substrate-level phos- f. Summarize the function of the Embden-Meyerhof, Entner-Doudoroff, phorylation when the phosphate on phosphoenolpyruvate (the and pentose phosphate pathways last intermediate of the pathway) is donated to ADP. This reac- g. Draw a simple diagram that shows the connection between the tion also yields pyruvate, the final product of the pathway. Entner-Doudoroff pathway and the Embden-Meyerhof pathway and ATP: the major energy currency of cells (section 10.2) the connection between the pentose phosphate pathway and the How NAD+ Works Embden-Meyerhof pathway The yields of ATP and NADH by the Embden-Meyerhof h. Create a table that shows which types of organisms use each of the pathway may be calculated. In the 6-carbon phase, two ATP are glycolytic pathways used to form fructose 1,6-bisphosphate. For each glyceraldehyde 3-phosphate transformed into pyruvate, one NADH and two ATP Microorganisms employ several metabolic pathways to catabo- are formed. Because two glyceraldehyde 3-phosphates arise from lize glucose to pyruvate in the cytosol, including (1) the Embden- a single glucose, the 3-carbon phase generates four ATP and two Meyerhof pathway, (2) the Entner-Doudoroff pathway, and NADH per glucose. Subtraction of the ATP used in the 6-carbon (3) the pentose phosphate pathway. We refer to these pathways phase from ATP produced by substrate-level phosphorylation in collectively as glycolytic pathways or as glycolysis (Greek the 3-carbon phase gives a net yield of two ATP per glucose. wil11886_ch11_228-264.indd 233 23/10/18 10:08 am  234 CHAPTER 11 | Catabolism: Energy Release and Conservation Glucose 1 C C C C C C Glucose is phosphorylated at the expense of one ATP, generating glucose 6-phosphate, a precursor ATP metabolite and the starting molecule for the pentose phosphate pathway. ADP PO4 Glucose 6-phosphate C 1 C C C C C Isomerization of glucose 6-phosphate (an aldehyde) to fructose 6-phosphate (a ketone and a precursor metabolite) PO4 Fructose 6-phosphate 1 C C C C C C ATP is consumed to phosphorylate C1 of fructose. ATP The cell is spending some of its energy currency in order to earn more in the next part ADP PO4 of the pathway. PO4 6 C phase 1 Fructose 1, 6-bisphosphate C C C C C C Dihydroxyacetone PO 3 C phase Fructose 1, 6-bisphosphate is split into two phosphate (DHAP) 4 3-carbon molecules, one of which is a precursor C C C metabolite. DHAP is readily converted to glyceraldehyde 3-phosphate. Glyceraldehyde 3-phosphate C C C PO4 Glyceraldehyde 3-phosphate e– NAD+ e– NAD+ Glyceraldehyde 3-phosphate is oxidized and simultaneously phosphorylated, generating a high- NADH + H+ NADH + H+ energy molecule. The electrons released reduce NAD+ to NADH. Pi Pi 1, 3-bisphosphoglycerate PO4 C C C PO4 1, 3-bisphosphoglycerate ADP ADP ATP is made by substrate-level phosphorylation. Another precursor metabolite is made. ATP ATP 3-phosphoglycerate C C C PO4 3-phosphoglycerate PO4 2-phosphoglycerate 2-phosphoglycerate C C C Another precursor metabolite is made. H2O H2O PO4 Phosphoenolpyruvate C C C Phosphoenolpyruvate ADP ADP Substrate-level phosphorylation yields another ATP and pyruvate, an important precursor molecule. In total, the oxidation of 1 glucose results in the formation of ATP ATP 2 pyruvate molecules, 2 NADH, and a net yield of 2 ATP. Pyruvate C C C Pyruvate Figure 11.5 Embden-Meyerhof Pathway. This is one of three pathways used to catabolize glucose to pyruvate, and it can function d­ uring aerobic respiration, anaerobic respiration, and fermentation. When used during respiration, the electrons accepted by NAD+ are transferred to an ­electron transport chain and are ultimately accepted by an exogenous electron acceptor. When used during fermentation (section 11.8), the electrons accepted by NAD+ are donated to an endogenous electron acceptor (e.g., pyruvate). The Embden-Meyerhof pathway also generates several precursor metabolites (shown in blue). MICRO INQUIRY Which reactions are examples of substrate-level phosphorylation? Thus the catabolism of glucose to pyruvate via the Embden- Entner-Doudoroff Pathway Meyerhof pathway can be represented by the following equation. The Entner-Doudoroff pathway is used by some Gram-­ Glucose + 2ADP + 2Pi + 2NAD → + negative bacteria, especially those found in soil. To date, very 2 pyruvate + 2ATP + 2NADH + 2H+ few Gram-positive bacteria have been found to use this pathway, with the intestinal bacterium Enterococcus faecalis being a rare How Glycolysis Works exception. It is not used by eukaryotes. wil11886_ch11_228-264.indd 234 23/10/18 10:08 am  11.4 Glucose to Pyruvate: The First Step 235 Glucose the Entner-Doudoroff pathways because it is important in bio- ATP synthesis as well as catabolism. Both eukaryotes and bacteria use ADP it to provide reducing power (as NADPH) and important precur- Glucose 6-phosphate sor metabolites for biosynthetic reactions. However, it has not yet NADP+ been found in archaea. NADPH + H+ The pentose phosphate pathway begins with a two-step oxi- 6-phosphogluconate Entner-Doudoroff pathway dative phase when glucose 6-phosphate is oxidized to 6-phos- H 2O phogluconate, which in turn is oxidized and decarboxylated to 2-keto-3-deoxy-6-phosphogluconate (KDPG) the 5-carbon sugar (i.e., a pentose sugar) ribulose 5-phosphate and CO2 (figure 11.7 and appendix II). Unlike the Embden- Meyerhof pathway where NAD+ accepts electrons, thereby gen- Pyruvate Glyceraldehyde 3-phosphate erating NADH, here NADP+ is the electron acceptor and NAD+ NADPH is produced. This leads to another important difference NADH + H+ between the two pathways because NADH donates its electrons ADP to the ETC so that energy can be conserved, while NADPH Further catabolism ATP of glyceraldehyde donates its electrons to biosynthetic reactions, which often con- 3-phosphate by sume energy. enzymes of the Embden-Meyerhof Following the oxidative phase, ribulose 5-phosphate is con- pathway. verted to a mixture of 3- to 7-carbon sugar phosphates. Two en- zymes play a central role in these transformations: (1) ADP transketolase catalyzes the transfer of 2-carbon groups, and (2) ATP transaldolase transfers a 3-carbon group from sedoheptulose Pyruvate 7-phosphate (a 7-carbon molecule) to glyceraldehyde 3-phos- Figure 11.6 The Entner-Doudoroff Pathway. phate (a 3-carbon molecule). The overall result is that three glu- MICRO INQUIRY For what kinds of reactions is NADPH used? cose 6-phosphates are converted to two fructose 6-phosphates, glyceraldehyde 3-phosphate, and three CO2 molecules, as shown in the following equation. The Entner-Doudoroff pathway replaces the 6-carbon 3 glucose 6-phosphate + 6NADP+ + 3H2O → phase of the Embden-Meyerhof pathway to yield pyruvate and 2 fructose 6-phosphate + glyceraldehyde 3-phosphate + glyceraldehyde 3-phosphate instead of two molecules of glycer- 3CO2 + 6NADPH + 6H+ aldehyde 3-phosphate. A key intermediate of the Entner- Doudoroff pathway has the long but descriptive name 2-keto- These intermediates are used in two ways. Fructose 6-phosphate 3-deoxy-6-phosphogluconate (KDPG), which is formed from can be changed back to glucose 6-phosphate while glyceralde- glucose by three reactions that consume one ATP and produce hyde 3-phosphate is converted to pyruvate by enzymes of the one NADPH (figure 11.6 and appendix II). KDPG is then Embden-Meyerhof pathway. Alternatively two glyceraldehyde cleaved to pyruvate and glyceraldehyde 3-phosphate. Bacteria 3-phosphates may combine to form fructose 1,6-bisphosphate, that use this pathway also have the enzymes that function in the which is eventually converted back into g­ lucose 6-phosphate. 3-carbon phase of the Embden-­Meyerhof pathway. These en- This results in the complete degradation of glucose 6-phos- zymes may be used to catabolize glyceraldehyde 3-phosphate phate to CO2 and the production of a great deal of NADPH. to form a second pyruvate molecule. If this occurs, two ATP and Glucose 6-phosphate + 12NADP+ + 7H2O → one NADH are formed. Thus the catabolism of one glucose 6CO2 + 12NADPH + 12H+ + Pi molecule to two pyruvates by way of the Entner-Doudoroff pathway coupled with the second half of the Embden-Meyerhof The pentose phosphate pathway is an important amphibolic pathway has a net yield of one ATP, one NADH, and one pathway because: (1) NADPH serves as a source of electrons for NADPH. During aerobic respiration, the NADH is used to the reduction of molecules during biosynthesis. Indeed, the pen- transport electrons to an ETC; the NADPH provides electrons tose phosphate pathway is the major source of reducing power for for anabolic ­reactions. cells, yielding two NADPH molecules for each glucose metabo- lized to pyruvate in this way. (2) The pathway produces two im- portant precursor metabolites: erythrose 4-phosphate and ribose Pentose Phosphate Pathway: A Major Producer 5-phosphate. Erythrose 4-phosphate is used to synthesize aromatic of Reducing Power for Anabolic Reactions amino acids and v­ itamin B6; ribose 5-phosphate is a major compo- The pentose phosphate pathway (also called the hexose nent of nucleic acids. Furthermore, when a micro­organism is monophosphate pathway) can be used aerobically or anaero­bically. growing on a 5-carbon sugar, the pathway can function biosyn- It may be used at the same time as either the Embden-Meyerhof or thetically to supply 6-carbon sugars (hexose sugars, such as the wil11886_ch11_228-264.indd 235 23/10/18 10:08 am  236 CHAPTER 11 | Catabolism: Energy Release and Conservation 1 Glucose 6-phosphate, an intermediate of the Embden-Meyerhof pathway and 2 6-Phosphogluconate is oxidized and a precursor metabolite, is oxidized. The decarboxylated. This produces CO2 and reaction provides reducing power in the more reducing power in the form of form of NADPH. NADPH. 3NADP+ 3NADPH + 3H+ 3NADP+ 3NADPH + 3H+ 3 glucose-6- P 3 6-phosphogluconate 3 ribulose-5- P (5 carbons) 3H2O 3CO2 Ribose-5- P Xylulose-5- P (5 carbons) (5 carbons) Transketolase 3 Sugar transformation reactions (blue arrows) are catalyzed by the enzymes transaldolase and transketolase. Some of the sugars can be used in Glyceraldehyde-3- P Sedoheptulose-7- P biosynthesis or to regenerate (3 carbons) (7 carbons) glucose 6-phosphate. They also can be further catabolized to pyruvate. Transaldolase Fructose-6- P Erythrose-4- P (6 carbons) (4 carbons) Xylulose-5- P Transketolase Fructose-6- P Glyceraldehyde-3- P EMP reactions Pi Fructose-6- P Fructose-1,6-bis P Pyruvate (6 carbons) Figure 11.7 The Pentose Phosphate Pathway. The catabolism of three glucose 6-phosphate molecules to two fructose 6-phosphates, a glyceraldehyde 3-phosphate, and three CO2 molecules is traced. Note that the pentose phosphate pathway generates several intermediates that are also intermediates of the Embden-Meyerhof pathway (EMP). These intermediates can be fed into the EMP with two results: (1) continued degradation to pyruvate or (2) regeneration of glucose 6-phosphate by gluconeogenesis. The pentose phosphate pathway also plays a major role in producing reducing power (NADPH) and several precursor metabolites (shown in blue) for biosynthesis. The sugar transformations are indicated with blue arrows. MICRO INQUIRY For what macromolecule is ribose 5-phosphate a precursor? glucose needed for peptidoglycan synthesis). (3) Intermediates in the pathway may be used to p­ roduce ATP. For instance, glyceral- Comprehension Check dehyde 3-phosphate can ­enter the 3-carbon phase of the Embden- 1. Summarize the major features of the Embden-Meyerhof, Entner- Meyerhof pathway. As it is degraded to pyruvate, two ATP are Doudoroff, and pentose phosphate pathways. Include the starting formed by substrate-level phosphorylation. Synthesis of points, the products of the pathways, the ATP yields, and the amino acids consumes many precursor metabolites (section 12.5); metabolic roles each pathway has. Synthesis of purines, pyrimidines, and nucleotides (section 12.6) 2. What is substrate-level phosphorylation? wil11886_ch11_228-264.indd 236 23/10/18 10:08 am  11.6 Electron Transport and Oxidative Phosphorylation (Step 3) Generate the Most ATP 237 TCA cycle enzymes are widely distributed among micro-­ 11.5 Pyruvate to Carbon Dioxide (Step 2) organisms. In bacteria and archaea, they are located in the cytosol. In eukaryotes, they are found in the mitochondrial matrix. The com- Is Accomplished by the Tricarboxylic plete cycle appears to be functional in many aerobic bacteria, ar- Acid Cycle chaea, free-living protists, and fungi. This is not surprising because the cycle plays an important role in energy conservation by produc- After reading this section, you should be able to: ing NADH and FADH2 (section 11.6). Even microorganisms that a. State the alternate names for the tricarboxylic acid (TCA) cycle lack the complete TCA cycle usually have most of its enzymes, be- b. Diagram the changes made to pyruvate as it is catabolized by the cause the TCA cycle is also a key source of precursor metabolites for TCA cycle use in biosynthesis. Anaplerotic reactions replace the precur- c. Identify those reactions of the TCA cycle that produce GTP and sor metabolites used for amino acid biosynthesis (section 12.5) NADH, generate precursor metabolites, or are redox reactions d. Calculate the yields of GTP, NADH, and FADH2 by the TCA cycle Comprehension Check e. Summarize the function of the TCA cycle 1. Identify the substrate and products of the TCA cycle. Describe its f. Diagram the connections between the various glycolytic pathways organization in general terms. What are its major functions? and the TCA cycle 2. What chemical intermediate links pyruvate to the TCA cycle? g. Locate the TCA cycle enzymes in bacterial, archaeal, and eukaryotic cells 3. How many times must the TCA cycle be performed to oxidize one molecule of glucose completely to six molecules of CO2? Why? In the glycolytic pathways, glucose is oxidized to pyruvate. Dur- 4. In what eukaryotic organelle is the TCA cycle found? Where is the ing aerobic respiration, the catabolic process continues by oxi- cycle located in bacterial and archaeal cells? dizing pyruvate to three CO2. The first step of this process 5. Why is it desirable for a microbe with the Embden-Meyerhof pathway employs a multienzyme system called the pyruvate dehydroge- and the TCA cycle also to have the pentose phosphate pathway? nase complex (PDH). PDH oxidizes and cleaves pyruvate to form one NADH, one CO2, and the 2-carbon molecule acetyl- coenzyme A (acetyl-CoA) (figure 11.8). The oxidization of a molecule to simultaneously release carbon as CO2 and NADH 11.6 Electron Transport and Oxidative (or other reduced electron carrier) is called oxidative decarboxy- lation. Acetyl-CoA is an energy-rich molecule because the bond Phosphorylation (Step 3) Generate that links acetic acid to coenzyme A (a thioester bond) has a large the Most ATP negative change in free energy when hydrolyzed. After reading this section, you should be able to: Acetyl-CoA then enters the tricarboxylic acid (TCA) cycle, also called the citric acid cycle or the Krebs cycle (figure 11.8 a. Compare and contrast the mitochondrial electron transport chain and appendix II). In the first reaction, acetyl-CoA is condensed (ETC) and bacterial ETCs with (i.e., added to) the 4-carbon intermediate oxaloacetate to b. Describe the chemiosmotic hypothesis form citrate, a molecule with six carbons. This reaction is fueled c. Correlate length of an ETC and the carriers in it with the magnitude by the cleavage of the high-energy thioester bond in acetyl-CoA. of the proton motive force (PMF) it generates Citrate is rearranged to give isocitrate, a more readily oxidized d. Explain how ATP synthase uses PMF to generate ATP alcohol. Isocitrate undergoes oxidative decarboxylation twice to e. Draw a simple diagram that shows the connections between the yield α-ketoglutarate (five carbons) and then succinyl-CoA (four glycolytic pathways, TCA cycle, ETC, and ATP synthesis carbons), another high-­energy molecule containing a thioester f. List the ways the PMF is used by bacterial cells in addition to ATP synthesis bond. Note that each decarboxylation is accompanied by the pro- g. Calculate the maximum possible ATP yields when glucose is completely duction of an NADH, so at this point two NADH and two CO2 catabolized to six molecules of CO2 during aerobic respiration molecules have been produced in the cycle. Succinyl-CoA is then converted to succinate; hydrolysis of the high-energy thioester During the oxidation of glucose to six CO2 molecules by bond in succinyl-CoA drives the synthesis of one GTP by substrate- glycolysis and the TCA cycle, as many as four ATP molecules level phosphorylation. GTP is a high-energy molecule function- are generated by substrate-level phosphorylation. Thus at this ally equivalent to ATP. It is used in protein synthesis and to make point, the work done by the cell has yielded relatively little ATP. other nucleoside triphosphates, including ATP. Two additional However, in oxidizing glucose, the cell has also generated lots of oxidation steps follow, yielding one FADH2 and one NADH. The NADH and FADH2. Both of these molecules have a relatively last oxidation step regenerates oxaloacetate, and as long as negative E′0 and can be used to conserve energy. In fact, most of there is a supply of acetyl-CoA, the cycle can repeat itself. In- the ATP generated during respiration comes from the energy spection of figure 11.8 shows that the TCA cycle generates two conserved when these electron carriers are oxidized by an ETC. CO2 molecules, three NADH molecules, one FADH2, and one We examine the mitochondrial electron transport chain first be- GTP for each acetyl-CoA molecule oxidized. How the cause it has been well studied and because it functions in fungi Krebs Cycle Works and many protists. We then turn to bacterial chains and a wil11886_ch11_228-264.indd 237 23/10/18 10:08 am  238 CHAPTER 11 | Catabolism: Energy Release and Conservation From glycolysis O C O– Pyruvate C O 1 Pyruvate is oxidatively decarboxylated (i.e., it loses a carbon in the form of CO2 and CH3 produces an NADH). The two remaining carbons are attached to coenzyme A by a high-energy bond. The energy in this bond NAD+ drives the next reaction. Acetyl-CoA is a precursor metabolite. 9 Malate is oxidized, 1 NADH + H+ generating more NADH and regenerating CO2 oxaloacetate, which is O needed to accept the two CoA carbons from acetyl-CoA C S CoA Acetyl-CoA 2 The two carbons of acetyl-CoA are and continue the cycle. combined with the four carbons of Oxaloacetate is also a CH3 oxaloacetate. This forms the precursor metabolite. Oxaloacetate Citrate 6-carbon molecule citrate. COO– COO– NADH + H+ C O 2 CH2 CH2 HO COO– C NAD+ COO– 3 Rearrangement of atoms CH2 to form isocitric acid. 9 COO– Malate 3 COO– Isocitric acid HO CH 6-carbon COO– 4-carbon stage HC stage CH2 COO– HC COO– TCA Cycle HO CH 8 H2O 8 Fumarate reacts COO– COO– NAD+ with H2O to 4 5-carbon form malate. CH NADH + H+ stage HC COO– CH2 CO2 COO– CoA CH2 4 Oxidative Fumarate 7 decarboxylation FADH2 COO– C O removes another carbon yielding CO2, FAD CH2 COO– NADH, and the O 5 7 Succinate is oxidized to 5-carbon precursor CH2 C O– α-ketoglutarate 6 NAD+ + CoA metabolite fumarate. FAD serves as the electron acceptor. COO– CH2 α-ketoglutarate. Succinate NADH + H+ CH2 6 CoA is cleaved from the high-energy GTP ADP CO2 molecule succinyl-CoA. The energy or C 5 Another oxidative decarboxylation released is used to form GTP, which GDP O S CoA releases the last carbon of glucose as can be used to make ATP or used CO2. More NADH is formed for use by Succinyl-CoA + directly to supply energy to processes Pi an ETC, and the 4-carbon precursor such as translation. metabolite succinyl-CoA is formed. Figure 11.8 The Tricarboxylic Acid Cycle. The TCA cycle is linked to glycolysis by a connecting reaction catalyzed by the pyruvate dehydrogenase complex. The reaction decarboxylates pyruvate and generates acetyl-CoA. The TCA cycle may be divided into three stages based on the size of its intermediates. The three stages are separated from one another by two oxidative decarboxylation reactions. Precursor metabolites are shown in blue. NADH and FADH2 are shown in purple; they can transfer electrons to an electron transport chain (ETC). MICRO INQUIRY What reaction provides the energy to fuel the condensation (joining) of the 4-carbon oxaloacetate with the 2-carbon acetyl-CoA to form citrate? wil11886_ch11_228-264.indd 238 23/10/18 10:08 am