Cellular Respiration: Harvesting Chemical Energy

Transcription

1 Chapter 9 Cellular Respiratin: Harvesting Chemical Energy Lecture Outline Overview: Life Is Wrk T perfrm their many tasks, living cells require energy frm utside surces. Energy enters mst ecsystems as sunlight and leaves as heat. In cntrast, the chemical elements essential fr life are recyled. Phtsynthesis generates xygen and rganic mlecules that the mitchndria f eukarytes (including plants and algae) use as fuel fr cellular respiratin. Cells harvest the chemical energy stred in rganic mlecules and use it t regenerate ATP, the mlecule that drives mst cellular wrk. Respiratin has three key pathways: glyclysis, the citric acid cycle, and xidative phsphrylatin. Cncept 9.1 Catablic pathways yield energy by xidizing rganic fuels. Catablic metablic pathways release the energy stred in cmplex rganic mlecules. Electrn transfer plays a majr rle in these pathways. The arrangement f atms f rganic mlecules represents ptential energy. Enzymes catalyze the systematic degradatin f rganic mlecules that are rich in energy t simpler waste prducts that have less energy. Sme f the released energy is used t d wrk; the rest is dissipated as heat. One type f catablic prcess, fermentatin, leads t the partial degradatin f sugars withut the use f xygen. A mre efficient and widespread catablic prcess, aerbic respiratin, cnsumes xygen as a reactant t cmplete the breakdwn f a variety f rganic mlecules. Mst eukarytic and many prkarytic rganisms can carry ut aerbic respiratin. Sme prkarytes use cmpunds ther than xygen as reactants in a similar prcess called anaerbic respiratin. Althugh cellular respiratin technically includes bth aerbic and anaerbic prcesses, the term is cmmnly used t refer nly t the aerbic prcess. Aerbic respiratin is similar in brad principle t the cmbustin f gasline in an autmbile engine after xygen is mixed with hydrcarbn fuel. Lecture Outline fr Campbell/Reece Bilgy, 8 th Editin, Pearsn Educatin, Inc. 9-1

2 Fd is the fuel fr respiratin. The exhaust is carbn dixide and water. The verall catablic prcess is: rganic cmpunds + O 2! CO 2 + H 2O + energy (ATP + heat). Carbhydrates, fats, and prteins can all be used as the fuel, but it is mst useful t cnsider glucse: C 6H 12O 6 + 6O 2! 6CO 2 + 6H 2O + energy (ATP + heat) The catablism f glucse is exergnic, with ΔG = 686 kcal per mle f glucse. Sme f this energy is used t prduce ATP, which can perfrm cellular wrk. Redx reactins release energy when electrns mve clser t electrnegative atms. Catablic pathways transfer the electrns stred in fd mlecules, releasing energy that is used t synthesize ATP. Reactins that result in the transfer f ne r mre electrns (e ) frm ne reactant t anther are xidatin-reductin reactins, r redx reactins. The lss f electrns frm a substance is called xidatin. The additin f electrns t anther substance is called reductin. Adding electrns is called reductin because negatively charged electrns added t an atm reduce the amunt f psitive charge f that atm. The frmatin f table salt frm sdium and chlride, Na + Cl! Na + + Cl, is a redx reactin. Sdium is xidized, and chlrine is reduced (its charge drps frm 0 t 1). Mre generally: Xe + Y! X + Ye. X, the electrn dnr, is the reducing agent and reduces Y by dnating an electrn t it. Y, the electrn recipient, is the xidizing agent and xidizes X by remving its electrn. Redx reactins require bth a dnr and an acceptr. Redx reactins als ccur when the transfer f electrns is nt cmplete but invlves a change in the degree f electrn sharing in cvalent bnds. In the cmbustin f methane t frm water and carbn dixide, the nnplar cvalent bnds f methane (C H) and xygen (O=O) are cnverted t plar cvalent bnds (C=O and O H). When methane reacts with xygen t frm carbn dixide, electrns end up farther away frm the carbn atm and clser t their new cvalent partners, the xygen atms, which are very electrnegative. In effect, the carbn atm has partially lst its shared electrns. Thus, methane has been xidized. The tw atms f the xygen mlecule (O 2) share their electrns equally. When xygen reacts with the hydrgen frm methane t frm water, the electrns f the cvalent bnds are drawn clser t the xygen. In effect, each xygen atm has partially gained electrns, and s the xygen mlecule has been reduced. Oxygen is very electrnegative and is ne f the mst ptent f all xidizing agents. Energy must be added t pull an electrn away frm an atm. The mre electrnegative the atm, the mre energy is required t take an electrn away frm it. Lecture Outline fr Campbell/Reece Bilgy, 8 th Editin, Pearsn Educatin, Inc. 9-2

3 An electrn lses ptential energy when it shifts frm a less electrnegative atm tward a mre electrnegative ne. A redx reactin that relcates electrns clser t xygen, such as the burning f methane, releases chemical energy that can d wrk. Organic fuel mlecules are xidized during cellular respiratin. Respiratin, the xidatin f glucse and ther mlecules in fd, is a redx prcess. In a series f reactins, glucse is xidized and xygen is reduced. The electrns lse ptential energy alng the way, and energy is released. Organic mlecules that cntain an abundance f hydrgen are excellent fuels. The bnds f these mlecules are a surce f hilltp electrns, whse energy may be released as the electrns fall dwn an energy gradient when they are transferred t xygen. As hydrgen is transferred frm glucse t xygen, the energy state f the electrn changes. In respiratin, the xidatin f glucse transfers electrns t a lwer energy state, releasing energy that becmes available fr ATP synthesis. The main energy fds, carbhydrates and fats, are reservirs f electrns assciated with hydrgen. These mlecules are stable because f the barrier f activatin energy. Withut this barrier, a fd mlecule like glucse wuld cmbine almst instantaneusly with O 2. If activatin energy is supplied by igniting glucse, it burns in air, releasing 686 kcal (2,870 kj) f heat per mle f glucse (abut 180 g). This reactin cannt happen at bdy temperatures. Instead, enzymes within cells lwer the barrier f activatin energy, allwing sugar t be xidized in a series f steps. The fall f electrns during respiratin is stepwise, via NAD + and an electrn transprt chain. Cellular respiratin des nt xidize glucse in a single step that transfers all the hydrgen in the fuel t xygen at ne time. Rather, glucse and ther fuels are brken dwn in a series f steps, each catalyzed by a specific enzyme. At key steps, electrns are stripped frm the glucse. In many xidatin reactins, the electrn is transferred with a prtn, as a hydrgen atm. The hydrgen atms are nt transferred directly t xygen but are passed first t a cenzyme called NAD + (nictinamide adenine dinucletide). As an electrn acceptr, NAD + functins as an xidizing agent during respiratin. Hw des NAD + trap electrns frm glucse? Dehydrgenase enzymes strip tw hydrgen atms frm the substrate (glucse), thus xidizing it. The enzyme passes tw electrns and ne prtn t NAD +. The ther prtn is released as H + t the surrunding slutin. By receiving tw electrns and nly ne prtn, NAD + has its charge neutralized when it is reduced t NADH. Lecture Outline fr Campbell/Reece Bilgy, 8 th Editin, Pearsn Educatin, Inc. 9-3

4 NAD + functins as the xidizing agent in many f the redx steps during the breakdwn f glucse. The electrns carried by NADH lse very little f their ptential energy in this prcess. Each NADH mlecule frmed during respiratin represents stred energy. This energy is tapped t synthesize ATP as electrns fall dwn an energy gradient frm NADH t xygen. Hw are electrns extracted frm glucse and stred in NADH finally transferred t xygen? Unlike the explsive release f heat energy that ccurs when H 2 and O 2 are cmbined (with a spark fr activatin energy), cellular respiratin uses an electrn transprt chain t break the fall f electrns t O 2 int several steps. The electrn transprt chain cnsists f several mlecules (primarily prteins) built int the inner membrane f a mitchndrin f eukarytic cells and the plasma membrane f aerbically respiring prkarytes. Electrns released frm fd are shuttled by NADH t the tp higher-energy end f the chain. At the bttm lwer-energy end, xygen captures the electrns alng with H + t frm water. Electrn transfer frm NADH t xygen is an exergnic reactin with a free-energy change f 53 kcal/ml. Electrns are passed t increasingly electrnegative mlecules in the chain until they reduce xygen, the mst electrnegative receptr. Each dwnhill carrier is mre electrnegative than, and thus capable f xidizing, its uphill neighbr, with xygen at the bttm f the chain. The electrns remved frm glucse by NAD + fall dwn an energy gradient in the electrn transprt chain t a far mre stable lcatin in the electrnegative xygen atm. In summary, during cellular respiratin, mst electrns travel the fllwing dwnhill rute: glucse! NADH! electrn transprt chain! xygen. The stages f cellular respiratin: a preview. Respiratin ccurs in three metablic stages: glyclysis, the citric acid cycle, and the electrn transprt chain and xidative phsphrylatin. Glyclysis ccurs in the cytsl. It begins catablism by breaking glucse int tw mlecules f pyruvate. The citric acid cycle ccurs in the mitchndrial matrix f eukarytic cells r in the cytplasm f prkarytes. It cmpletes the breakdwn f glucse by xidizing a derivative f pyruvate t carbn dixide. Several steps in glyclysis and the citric acid cycle are redx reactins in which dehydrgenase enzymes transfer electrns frm substrates t NAD +, frming NADH. In the third stage f respiratin, the electrn transprt chain accepts electrns frm the breakdwn prducts f the first tw stages (mst ften via NADH). In the electrn transprt chain, the electrns mve frm mlecule t mlecule until they cmbine with mlecular xygen and hydrgen ins t frm water. As the electrns are passed alng the chain, the energy released at each step in the chain is stred in a frm the mitchndrin (r prkarytic cell) can use t make ATP. Lecture Outline fr Campbell/Reece Bilgy, 8 th Editin, Pearsn Educatin, Inc. 9-4

5 This mde f ATP synthesis is called xidative phsphrylatin because it is pwered by the redx reactins f the electrn transprt chain. In eukarytic cells, the inner membrane f the mitchndrin is the site f electrn transprt and chemismsis, the prcesses that tgether cnstitute xidative phsphrylatin. In prkarytes, these prcesses take place in the plasma membrane. Oxidative phsphrylatin prduces almst 90% f the ATP generated by respiratin. Sme ATP is als frmed directly during glyclysis and the citric acid cycle by substrate-level phsphrylatin, in which an enzyme transfers a phsphate grup frm an rganic substrate mlecule t ADP, frming ATP. Fr each mlecule f glucse degraded t carbn dixide and water by respiratin, the cell makes as many as 38 ATP, each with 7.3 kcal/ml f free energy. Respiratin uses the small steps in the respiratry pathway t break the large denminatin f energy cntained in glucse int the small change f ATP. The quantity f energy in ATP is mre apprpriate fr the energy level f wrk required in the cell. Cncept 9.2 Glyclysis harvests chemical energy by xidizing glucse t pyruvate. During glyclysis, glucse, a six-carbn sugar, is split int tw three-carbn sugars. These smaller sugars are then xidized and rearranged t frm tw mlecules f pyruvate, the inized frm f pyruvic acid. Each f the ten steps in glyclysis is catalyzed by a specific enzyme. These steps can be divided int tw phases. 1. In the energy investment phase, the cell spends ATP. 2. In the energy payff phase, this investment is repaid with interest. ATP is prduced by substrate-level phsphrylatin, and NAD + is reduced t NADH by electrns released by the xidatin f glucse. The net yield frm glyclysis is 2 ATP and 2 NADH per glucse. N CO 2 is prduced during glyclysis. Glyclysis can ccur whether r nt O 2 is present. If O 2 is present, the chemical energy stred in pyruvate and NADH can be extracted by the citric acid cycle and xidative phsphrylatin. Cncept 9.3 The citric acid cycle cmpletes the energy-yielding xidatin f rganic mlecules. Mre than three-quarters f the riginal energy in glucse is still present in the tw mlecules f pyruvate. If mlecular xygen is present in eukarytic cells, pyruvate enters the mitchndrin, where enzymes f the citric acid cycle cmplete the xidatin f the rganic fuel t carbn dixide. In prkarytic cells, this prcess ccurs in the cytplasm. Lecture Outline fr Campbell/Reece Bilgy, 8 th Editin, Pearsn Educatin, Inc. 9-5

6 After pyruvate enters the mitchndrin via active transprt, it is cnverted t a cmpund called acetyl cenzyme A, r acetyl CA. This step, the junctin between glyclysis and the citric acid cycle, is accmplished by a multienzyme cmplex that catalyzes three reactins. 1. A carbxyl grup is remved as CO 2. The carbn dixide is fully xidized and thus has little chemical energy. 2. The remaining tw-carbn fragment is xidized t frm acetate. An enzyme transfers the pair f electrns t NAD + t frm NADH. 3. Acetate cmbines with cenzyme A t frm the very reactive mlecule acetyl CA. Due t the chemical nature f the CA grup, a sulfur-cntaining cmpund derived frm a B vitamin, acetyl CA has a high ptential energy. In ther wrds, the reactin f acetyl CA t yield lwer-energy prducts is highly exergnic. Acetyl CA is nw ready t feed its acetyl grup int the citric acid cycle fr further xidatin. The citric acid cycle is als called the tricarbxylic acid cycle r the Krebs cycle. The latter name hnrs Hans Krebs, wh was largely respnsible fr elucidating the cycle s pathways in the 1930s. The citric acid cycle xidizes rganic fuel derived frm pyruvate. Three CO 2 mlecules are released, including the ne released during the cnversin f pyruvate t acetyl CA. The cycle generates ne ATP per turn by substrate-level phsphrylatin. Mst f the chemical energy is transferred t NAD + and a related electrn carrier, the cenzyme FAD, during the redx reactins. The reduced cenzymes, NADH and FADH 2, transfer high-energy electrns t the electrn transprt chain. The citric acid cycle has eight steps, each catalyzed by a specific enzyme. The acetyl grup f acetyl CA jins the cycle by cmbining with the cmpund xalacetate, frming citrate. The next seven steps decmpse the citrate back t xalacetate. It is the regeneratin f xalacetate that makes this prcess a cycle. Fr each acetyl grup that enters the cycle, 3 NAD + are reduced t NADH. In ne step, electrns are transferred t FAD instead f NAD +. Then FAD accepts 2 electrns and 2 prtns t becme FADH 2. In the cells f plants, bacteria, and a few animal tissues, the citric acid cycle frms an ATP mlecule by substrate-level phsphrylatin. In mst animal tissue cells, guansine triphsphate (GTP) is frmed by the same prcess f substrate-level phsphrylatin. GTP may be used t synthesize an ATP r t directly pwer wrk in the cell. The utput frm this step is the nly ATP generated directly by the citric acid cycle. Mst f the ATP prduced by respiratin results frm xidative phsphrylatin, as the NADH and FADH 2 prduced by the citric acid cycle relay the electrns extracted frm fd t the electrn transprt chain. Lecture Outline fr Campbell/Reece Bilgy, 8 th Editin, Pearsn Educatin, Inc. 9-6

7 This prcess supplies the necessary energy fr the phsphrylatin f ADP t ATP. Cncept 9.4 During xidative phsphrylatin, chemismsis cuples electrn transprt t ATP synthesis. Only 4 f 38 ATP ultimately prduced by the respiratin f glucse are prduced by substratelevel phsphrylatin. Tw ATP are prduced during glyclysis, and 2 ATP are prduced during the citric acid cycle. NADH and FADH 2 accunt fr mst f the energy extracted frm glucse. These reduced cenzymes link glyclysis and the citric acid cycle t xidative phsphrylatin, which uses energy released by the electrn transprt chain t pwer ATP synthesis. The inner mitchndrial membrane cuples electrn transprt t ATP synthesis. The electrn transprt chain is a cllectin f mlecules embedded in the cristae, the flded inner membrane f the mitchndrin. In prkarytes, the electrn transprt chain is lcated in the plasma membrane. The flding f the inner membrane t frm cristae increases its surface area, prviding space fr thusands f cpies f the chain in each mitchndrin. Mst cmpnents f the chain are prteins that exist in multiprtein cmplexes numbered I IV. Tightly bund t these prteins are prsthetic grups, nnprtein cmpnents essential fr catalysis. Electrns drp in free energy as they pass dwn the electrn transprt chain. During electrn transprt alng the chain, electrn carriers alternate between reduced and xidized states as they accept and dnate electrns. Each cmpnent f the chain becmes reduced when it accepts electrns frm its uphill neighbr, which is less electrnegative. It then returns t its xidized frm as it passes electrns t its mre electrnegative dwnhill neighbr. Electrns carried by NADH are transferred t the first mlecule in the electrn transprt chain, a flavprtein. In the next redx reactin, the flavprtein returns t its xidized frm as it passes electrns t an irn-sulfur prtein. The irn-sulfur prtein then passes the electrns t a cmpund called ubiquinne, a small hydrphbic mlecule and the nly member f the electrn transprt chain that is nt a prtein. Mst f the remaining electrn carriers between ubiquinne and xygen are prteins called cytchrmes. The prsthetic grup f each cytchrme is a heme grup with an irn atm that accepts and dnates electrns. The last cytchrme f the chain, cyt a 3, passes its electrns t xygen, which is very electrnegative. Each xygen atm als picks up a pair f hydrgen ins frm the aqueus slutin t frm water. Lecture Outline fr Campbell/Reece Bilgy, 8 th Editin, Pearsn Educatin, Inc. 9-7

8 The electrns carried by FADH 2 have lwer free energy and are added at a lwer energy level than thse carried by NADH. The electrn transprt chain prvides abut ne-third less energy fr ATP synthesis when the electrn dnr is FADH 2 rather than NADH. The electrn transprt chain generates n ATP directly. Its functin is t break the large free-energy drp frm fd t xygen int a series f smaller steps that release energy in manageable amunts. Chemismsis cuples electrn transprt and energy release t ATP synthesis. A prtein cmplex in the cristae, ATP synthase, actually makes ATP frm ADP and P i. ATP synthase wrks like an in pump running in reverse. In pumps usually use ATP as an energy surce t transprt ins against their gradients. Enzymes can catalyze a reactin in either directin, depending n the ΔG fr the reactin, which is affected by the lcal cncentratins f reactants and prducts. Rather than hydrlyzing ATP t pump prtns against their cncentratin gradient, under the cnditins f cellular respiratin, ATP synthase uses the energy f an existing in gradient t pwer ATP synthesis. The pwer surce fr the ATP synthase is a difference in the cncentratins f H + n ppsite sides f the inner mitchndrial membrane. This is als a ph gradient. This prcess, in which energy stred in the frm f a hydrgen in gradient acrss a membrane is used t drive cellular wrk such as the synthesis f ATP, is called chemismsis. Here, smsis refers t the flw f H + acrss a membrane. Frm studying the structure f ATP synthase, scientists have learned hw the flw f H + thrugh this large enzyme pwers ATP generatin. ATP synthase is a multisubunit cmplex with fur main parts, each made up f multiple plypeptides. Prtns mve ne by ne int binding sites n ne f the parts (the rtr), causing it t spin in a way that catalyzes ATP prductin frm ADP and inrganic phsphate. ATP synthase is the smallest mlecular rtary mtr knwn in nature. Part f the cmplex actually spins arund in the membrane when the reactin prceeds in the directin f ATP hydrlysis. Bichemists assumed that the same rtatinal mechanism was respnsible fr ATP synthesis, but they lacked experimental evidence. In 2004, nantechnlgy techniques (invlving cntrl f matter n the mlecular scale) were used t demnstrate that the directin f rtatin f ne part f the cmplex in relatin t anther is slely respnsible fr either ATP synthesis r ATP hydrlysis by this enzyme. Hw des the inner mitchndrial membrane r the prkarytic plasma membrane generate and maintain the H + gradient that drives ATP synthesis in the ATP synthase prtein cmplex? Establishing the H + gradient is the functin f the electrn transprt chain. The chain is an energy cnverter that uses the exergnic flw f electrns t pump H + acrss the membrane frm the mitchndrial matrix int the intermembrane space. The H + has a tendency t diffuse dwn its gradient. The ATP synthase mlecules are the nly place where H + can diffuse back t the matrix. Lecture Outline fr Campbell/Reece Bilgy, 8 th Editin, Pearsn Educatin, Inc. 9-8

9 The exergnic flw f H + is used by the enzyme t generate ATP. This cupling f the redx reactins f the electrn transprt chain t ATP synthesis is an example f chemismsis. Hw des the electrn transprt chain pump prtns? Certain members f the electrn transprt chain accept and release H + alng with electrns. At certain steps alng the chain, electrn transfers cause H + t be taken up and released int the surrunding slutin. The electrn carriers are spatially arranged in the membrane in such a way that prtns are accepted frm the mitchndrial matrix and depsited in the intermembrane space. The H + gradient that results is the prtn-mtive frce, a gradient with the capacity t d wrk. The frce drives H + back acrss the membrane thrugh the specific H + channels prvided by ATP synthases. Chemismsis is an energy-cupling mechanism that uses energy stred in the frm f an H + gradient acrss a membrane t drive cellular wrk. In mitchndria, the energy fr prtn gradient frmatin cmes frm exergnic redx reactins, and ATP synthesis is the wrk perfrmed. Chemismsis in chlrplasts als generates ATP, but light drives the electrn flw dwn an electrn transprt chain and H + gradient frmatin. Prkarytes generate H + gradients acrss their plasma membrane. Prkarytes use the prtn-mtive frce nt nly t generate ATP but als t pump nutrients and waste prducts acrss the membrane and t rtate their flagella. Here is an accunting f ATP prductin by cellular respiratin. During cellular respiratin, mst energy flws as fllws: glucse! NADH! electrn transprt chain! prtn-mtive frce! ATP. Let s cnsider the prducts generated when cellular respiratin xidizes a mlecule f glucse t six mlecules f CO 2. Fur ATP mlecules are prduced by substrate-level phsphrylatin during glyclysis and the citric acid cycle. Many mre ATP mlecules are generated by xidative phsphrylatin. Each NADH frm the citric acid cycle and the cnversin f pyruvate cntributes enugh energy t the prtn-mtive frce t generate a maximum f 3 ATP. There are three reasns we cannt state an exact number f ATP mlecules generated by ne mlecule f glucse. 1. Phsphrylatin and the redx reactins are nt directly cupled t each ther, s the rati f the number f NADH t the number f ATP is nt a whle number. " One NADH results in 10 H + being transprted acrss the inner mitchndrial membrane. " Between 3 and 4 H + must reenter the mitchndrial matrix via ATP synthase t generate 1 ATP. " Therefre, 1 NADH generates enugh prtn-mtive frce fr the synthesis f ATP. " We rund ff and say that 1 NADH generates 3 ATP. Lecture Outline fr Campbell/Reece Bilgy, 8 th Editin, Pearsn Educatin, Inc. 9-9

10 " The citric acid cycle als supplies electrns t the electrn transprt chain via FADH 2, but because it enters later in the chain, each mlecule f this electrn carrier is respnsible fr the transprt f nly enugh H + fr the synthesis f ATP. " There is als a slight energetic cst f mving the ATP frmed in the mitchndrin ut int the eukarytic cytplasm where it will be used. 2. The ATP yield varies slightly depending n the type f shuttle used t transprt electrns frm the cytsl int the mitchndrin. " The mitchndrial inner membrane is impermeable t NADH, s the tw electrns f the NADH prduced in glyclysis must be cnveyed int the mitchndrin by ne f several electrn shuttle systems. " In sme shuttle systems, the electrns are passed t NAD +, which generates 3 ATP. In thers, the electrns are passed t FAD, which generates nly 2 ATP. 3. The prtn-mtive frce generated by the redx reactins f respiratin may drive ther kinds f wrk, such as mitchndrial uptake f pyruvate frm the cytsl. " If all the prtn-mtive frce generated by the electrn transprt chain were used t drive ATP synthesis, ne glucse mlecule culd generate a maximum f 34 ATP by xidative phsphrylatin plus 4 ATP (net) frm substrate-level phsphrylatin t give a ttal yield f ATP (depending n the efficiency f the shuttle). Hw efficient is respiratin in generating ATP? Cmplete xidatin f glucse releases 686 kcal/ml. Phsphrylatin f ADP t frm ATP requires at least 7.3 kcal/ml. Efficiency f respiratin is 7.3 kcal/ml times 38 ATP/glucse divided by 686 kcal/ml glucse, which equals 0.4, r 40%. Apprximately 60% f the energy frm glucse is lst as heat. Sme f that heat is used t maintain ur high bdy temperature (37 C). Cellular respiratin is remarkably efficient in energy cnversin. Fr example, the mst efficient autmbile cnverts nly abut 25% f the energy stred in gasline t energy that mves the car. Cncept 9.5 Fermentatin and anaerbic respiratin enable sme cells t prduce ATP withut the use f xygen. Withut electrnegative xygen t pull electrns dwn the transprt chain, xidative phsphrylatin ceases. Hwever, there are tw general mechanisms by which certain cells can xidize rganic fuel and generate ATP withut the use f xygen: fermentatin and anaerbic respiratin. An electrn transprt chain is present in aerbic respiratin but nt in fermentatin. Anaerbic respiratin takes place in rganisms that have an electrn transprt chain but d nt use xygen as a final electrn acceptr at the end f the chain. Sme sulfate-reducing marine bacteria, fr instance, use the electrnegative sulfate in (SO 4 2-) at the end f their respiratry chain. Operatin f the chain builds up a prtn-mtive frce used t prduce ATP, but H 2S (hydrgen sulfide) is prduced as a by-prduct rather than H 2O (water). Lecture Outline fr Campbell/Reece Bilgy, 8 th Editin, Pearsn Educatin, Inc. 9-10

11 Fermentatin prvides a mechanism by which sme cells can xidize rganic fuel and generate ATP withut the use f xygen r any electrn transprt chain (that is, withut cellular respiratin). In glyclysis, glucse is xidized t tw pyruvate mlecules with NAD + as the xidizing agent. Glyclysis is exergnic and prduces 2 ATP (net) by substrate-level phsphrylatin. If xygen is present, additinal ATP can be generated when NADH delivers its electrns t the electrn transprt chain. Hwever, glyclysis generates 2 ATP whether xygen is present (aerbic) r nt (anaerbic). Fermentatin can generate ATP frm glucse by substrate-level phsphrylatin as lng as there is a supply f NAD + t accept electrns during the xidatin step f glyclysis. If the NAD + pl is exhausted, glyclysis shuts dwn. Under aerbic cnditins, NADH transfers its electrns t the electrn transfer chain, recycling NAD +. Fermentatin pathways recycle NAD + by transferring electrns frm NADH t pyruvate r derivatives f pyruvate. In alchl fermentatin, pyruvate is cnverted t ethanl in tw steps. 1. Pyruvate is cnverted t a tw-carbn cmpund, acetaldehyde, by the remval f CO Acetaldehyde is reduced by NADH t ethanl. This prcess regenerates the supply f NAD + needed fr the cntinuatin f glyclysis. Alchl fermentatin by yeast is used in brewing, baking, and winemaking. During lactic acid fermentatin, pyruvate is reduced directly by NADH t frm lactate (the inized frm f lactic acid) withut the release f CO 2. Lactic acid fermentatin by sme fungi and bacteria is used t make cheese and ygurt. Human muscle cells switch frm aerbic respiratin t lactic acid fermentatin t generate ATP when O 2 is scarce. This may ccur in the early stages f strenuus exercise. The waste prduct, lactate, was previusly thught t cause muscle fatigue and pain, but recent research suggests instead that increased levels f ptassium ins (K + ) may be t blame; lactate appears t enhance muscle perfrmance. Excess lactate is gradually carried away by the bld t the liver, where it is cnverted back t pyruvate by liver cells. Fermentatin and cellular respiratin are cmpared. Fermentatin and cellular respiratin are anaerbic and aerbic alternatives, respectively, fr prducing ATP frm sugars. Bth use glyclysis t xidize sugars t pyruvate with a net prductin f 2 ATP by substrate-level phsphrylatin. Bth use NAD + as an xidizing agent t accept electrns frm fd during glyclysis. The tw prcesses differ in their mechanism fr xidizing NADH t NAD +, which is required t sustain glyclysis. In fermentatin, the electrns f NADH are passed t an rganic mlecule such as pyruvate (lactic acid fermentatin) r acetaldehyde (alchl fermentatin), in rder t regenerate NAD +. In cellular respiratin, the electrns f NADH are ultimately passed t O 2, generating ATP by xidative phsphrylatin. Lecture Outline fr Campbell/Reece Bilgy, 8 th Editin, Pearsn Educatin, Inc. 9-11

12 Mre ATP is generated frm the xidatin f pyruvate in the citric acid cycle. Withut xygen, the energy still stred in pyruvate is unavailable t the cell. Under aerbic respiratin, a mlecule f glucse yields 38 ATP, but the same mlecule f glucse yields nly 2 ATP under anaerbic respiratin. Organisms vary in the pathways available t them t break dwn sugars. Obligate anaerbes carry ut nly fermentatin r anaerbic respiratin and cannt survive in the presence f xygen. A few cell types, such as the cells f the vertebrate brain, can carry ut nly aerbic xidatin f pyruvate, nt fermentatin. Yeast and many bacteria are facultative anaerbes that can survive using either fermentatin r respiratin. At a cellular level, human muscle cells can behave as facultative anaerbes. Fr facultative anaerbes, pyruvate is a frk in the metablic rad that leads t tw alternative rutes. Under aerbic cnditins, pyruvate is cnverted t acetyl CA and xidatin cntinues in the citric acid cycle. Under anaerbic cnditins, pyruvate serves as an electrn acceptr t recycle NAD +. T make the same amunt f ATP, a facultative anaerbe must cnsume sugar at a much faster rate when fermenting than when respiring. The rle f glyclysis in bth fermentatin and respiratin has an evlutinary basis. Ancient prkarytes used glyclysis t make ATP lng befre xygen was present in Earth s atmsphere. The ldest bacterial fssils are mre than 3.5 billin years ld, appearing lng befre appreciable quantities f O 2 accumulated in the atmsphere abut 2.7 billin years ag. Cyanbacteria prduced this O 2 as a by-prduct f phtsynthesis. The first prkarytes may have generated ATP exclusively frm glyclysis, which des nt require xygen. The fact that glyclysis is a ubiquitus metablic pathway and ccurs in the cytsl withut membrane-enclsed rganelles suggests that this pathway evlved very early in the histry f life n Earth. Cncept 9.6 Glyclysis and the citric acid cycle cnnect t many ther metablic pathways. Glyclysis and the citric acid cycle are majr intersectins f varius catablic and anablic (bisynthetic) pathways. A variety f rganic mlecules can be used t make ATP. Glyclysis can accept a wide range f carbhydrates fr catablism. Plysaccharides like starch r glycgen can be hydrlyzed t glucse mnmers that enter glyclysis and the citric acid cycle. The digestin f disaccharides, including sucrse, prvides glucse and ther mnsaccharides as fuel fr respiratin. Lecture Outline fr Campbell/Reece Bilgy, 8 th Editin, Pearsn Educatin, Inc. 9-12

13 The ther tw majr fuels, prteins and fats, can als enter the respiratry pathways used by carbhydrates. Prteins must first be digested t individual amin acids. Many f the amin acids are used by the rganism t build new prteins. Amin acids that will be catablized must have their amin grups remved via deaminatin. The nitrgenus waste is excreted as ammnia, urea, r anther waste prduct. The carbn skeletns are mdified by enzymes and enter as intermediaries int glyclysis r the citric acid cycle, depending n their structure. Catablism can als harvest energy stred in fats btained frm fd r frm strage cells in the bdy. Fats must be digested t glycerl and fatty acids. Glycerl can be cnverted t glyceraldehyde phsphate, an intermediate f glyclysis. The rich energy f fatty acids is accessed as fatty acids are split int tw-carbn fragments via beta xidatin. These mlecules enter the citric acid cycle as acetyl CA. NADH and FADH 2 are als generated during beta xidatin; they can enter the electrn transprt chain, leading t further ATP prductin. A gram f fat xidized by respiratin generates twice as much ATP as a gram f carbhydrate. The metablic pathways f respiratin als play a rle in anablic pathways f the cell. In additin t calries, fd must prvide the carbn skeletns that cells require t make their wn mlecules. Sme rganic mnmers btained frm digestin can be used directly. Intermediaries in glyclysis and the citric acid cycle can be diverted t anablic pathways as precursrs frm which the cell can synthesize the mlecules it requires. Fr example, a human cell can synthesize abut half the 20 different amin acids by mdifying cmpunds frm the citric acid cycle. The rest are essential amin acids that must be btained in the diet. Glucse can be synthesized frm pyruvate; fatty acids can be synthesized frm acetyl CA. Anablic, r bisynthetic, pathways d nt generate ATP but instead cnsume it. Glyclysis and the citric acid cycle functin as metablic interchanges that enable cells t cnvert ne kind f mlecule t anther as needed. Fr example, excess carbhydrates and prteins can be cnverted t fats thrugh intermediaries f glyclysis and the citric acid cycle. If we eat mre fd than we need, we stre fat even if ur diet is fat-free. Metablism is remarkably versatile and adaptable. Feedback mechanisms cntrl cellular respiratin. Basic principles f supply and demand regulate the metablic ecnmy. If a cell has an excess f a certain amin acid, it typically uses feedback inhibitin t prevent the diversin f intermediary mlecules frm the citric acid cycle t the synthesis pathway f that amin acid. Lecture Outline fr Campbell/Reece Bilgy, 8 th Editin, Pearsn Educatin, Inc. 9-13

14 The rate f catablism is als regulated, typically by the level f ATP in the cell. If ATP levels drp, catablism speeds up t prduce mre ATP. When there is plenty f ATP t meet demand, respiratin slws dwn, sparing valuable rganic mlecules fr ther functins. Cntrl f catablism is based mainly n regulating the activity f enzymes at strategic pints in the catablic pathway. One strategic pint ccurs in the third step f glyclysis, catalyzed by phsphfructkinase, an enzyme that functins as the pacemaker f respiratin. Phsphfructkinase catalyzes the earliest step that irreversibly cmmits the substrate t glyclysis. Phsphfructkinase is an allsteric enzyme with receptr sites fr specific inhibitrs and activatrs. Phsphfructkinase is inhibited by ATP and stimulated by AMP (derived frm ADP). When ATP levels are high, inhibitin f this enzyme slws glyclysis. As ATP levels drp and ADP and AMP levels rise, the enzyme becmes active again and glyclysis speeds up. Citrate, the first prduct f the citric acid cycle, is als an inhibitr f phsphfructkinase. This synchrnizes the rate f glyclysis and the citric acid cycle. If intermediaries frm the citric acid cycle are diverted t ther uses (fr example, amin acid synthesis), glyclysis speeds up t replace these mlecules. Metablic balance is augmented by the cntrl f ther enzymes at ther key lcatins in glyclysis and the citric acid cycle. Cells are thrifty, expedient, and respnsive in their metablism. Cellular respiratin functins in the brad cntext f energy flw and chemical cycling in ecsystems. The energy that keeps us alive is released, nt prduced, by cellular respiratin. Lecture Outline fr Campbell/Reece Bilgy, 8 th Editin, Pearsn Educatin, Inc. 9-14