Chapter 9

Cellular Respiration: Harvesting Chemical Energy

Lecture Outline
Overview: Life Is Work
To perform their many tasks, living cells require energy from outside sources. Energy enters most ecosystems as sunlight and leaves as heat. In contrast, the chemical elements essential for life are recyled. Photosynthesis generates oxygen and organic molecules that the mitochondria of eukaryotes (including plants and algae) use as fuel for cellular respiration. ells harvest the chemical energy stored in organic molecules and use it to regenerate !TP, the molecule that drives most cellular "ork. #espiration has three key path"ays$ glycolysis, the citric acid cycle, and oxidative phosphorylation.

Concept 9 ! Cata"olic pathways yiel# energy "y o$i#i%ing organic fuels

ata%olic meta%olic path"ays release the energy stored in complex organic molecules. Electron transfer plays a ma&or role in these path"ays. The arrangement of atoms of organic molecules represents potential energy. En'ymes cataly'e the systematic degradation of organic molecules that are rich in energy to simpler "aste products that have less energy. (ome of the released energy is used to do "ork) the rest is dissipated as heat. *ne type of cata%olic process, fermentation, leads to the partial degradation of sugars "ithout the use of oxygen. ! more efficient and "idespread cata%olic process, aero"ic respiration& consumes oxygen as a reactant to complete the %reakdo"n of a variety of organic molecules. o +ost eukaryotic and many prokaryotic organisms can carry out aero%ic respiration. o o (ome prokaryotes use compounds other than oxygen as reactants in a similar process called anaerobic respiration. !lthough cellular respiration technically includes %oth aero%ic and anaero%ic processes, the term is commonly used to refer only to the aero%ic process.

!ero%ic respiration is similar in %road principle to the com%ustion of gasoline in an automo%ile engine after oxygen is mixed "ith hydrocar%on fuel.
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Lecture Outline for Campbell/Reece Biology, 8th Edition, Pearson Education, Inc.

,ood is the fuel for respiration. The exhaust is car%on dioxide and "ater.

The overall cata%olic process is$ organic compounds - *. *. - /.* - energy (!TP heat). ar%ohydrates, fats, and proteins can all %e used as the fuel, %ut it is most useful to consider glucose$ 0/1.*0 - 0*. 0 *. - 0/.* - energy (!TP - heat) The cata%olism of glucose is exergonic, "ith G 2 030 kcal per mole of glucose. (ome of this energy is used to produce !TP, "hich can perform cellular "ork. ata%olic path"ays transfer the electrons stored in food molecules, releasing energy that is used to synthesi'e !TP. #eactions that result in the transfer of one or more electrons ( e) from one reactant to another are oxidation4reduction reactions, or re#o$ reactions. o The loss of electrons from a su%stance is called o$i#ation. o The addition of electrons to another su%stance is called re#uction. o Adding electrons is called reduction %ecause negatively charged electrons added to an atom reduce the amount of positive charge of that atom. The formation of ta%le salt from sodium and chloride, 5a - l 5a- - l, is a redox reaction. o (odium is oxidi'ed, and chlorine is reduced (its charge drops from 6 to 1). +ore generally$ 7e - 8 7 - 8e. o 7, the electron donor, is the re#ucing agent and reduces 8 %y donating an electron to it. o 8, the electron recipient, is the o$i#i%ing agent and oxidi'es 7 %y removing its electron. #edox reactions require %oth a donor and an acceptor. #edox reactions also occur "hen the transfer of electrons is not complete %ut involves a change in the degree of electron sharing in covalent %onds. In the com%ustion of methane to form "ater and car%on dioxide, the nonpolar covalent %onds of methane ( 9/) and oxygen (*2*) are converted to polar covalent %onds ( 2* and *9 /). :hen methane reacts "ith oxygen to form car%on dioxide, electrons end up farther a"ay from the car%on atom and closer to their ne" covalent partners, the oxygen atoms, "hich are very electronegative. o In effect, the car%on atom has partially ;lost< its shared electrons. Thus, methane has %een oxidi'ed. The t"o atoms of the oxygen molecule (*.) share their electrons equally. :hen oxygen reacts "ith the hydrogen from methane to form "ater, the electrons of the covalent %onds are dra"n closer to the oxygen. o In effect, each oxygen atom has partially ;gained< electrons, and so the oxygen molecule has %een reduced. o *xygen is very electronegative and is one of the most potent of all oxidi'ing agents. Energy must %e added to pull an electron a"ay from an atom. The more electronegative the atom, the more energy is required to take an electron a"ay from
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Redox reactions release energy when electrons move closer to electronegative atoms.

Lecture Outline for Campbell/Reece Biology, 8th Edition, Pearson Education, Inc.

it. !n electron loses potential energy "hen it shifts from a less electronegative atom to"ard a more electronegative one. ! redox reaction that relocates electrons closer to oxygen, such as the %urning of methane, releases chemical energy that can do "ork. Organic fuel molecules are oxidized during cellular respiration. #espiration, the oxidation of glucose and other molecules in food, is a redox process. In a series of reactions, glucose is oxidi'ed and oxygen is reduced. The electrons lose potential energy along the "ay, and energy is released. *rganic molecules that contain an a%undance of hydrogen are excellent fuels. The %onds of these molecules are a source of ;hilltop< electrons, "hose energy may %e released as the electrons ;fall< do"n an energy gradient "hen they are transferred to oxygen. !s hydrogen is transferred from glucose to oxygen, the energy state of the electron changes. In respiration, the oxidation of glucose transfers electrons to a lo"er energy state, releasing energy that %ecomes availa%le for !TP synthesis. The main energy foods, car%ohydrates and fats, are reservoirs of electrons associated "ith hydrogen. These molecules are sta%le %ecause of the %arrier of activation energy. o :ithout this %arrier, a food molecule like glucose "ould com%ine almost instantaneously "ith *.. o o o If activation energy is supplied %y igniting glucose, it %urns in air, releasing 030 kcal (.,3=6 k>) of heat per mole of glucose (a%out 136 g). This reaction cannot happen at %ody temperatures. Instead, en'ymes "ithin cells lo"er the %arrier of activation energy, allo"ing sugar to %e oxidi'ed in a series of steps.

The fall of electrons during respiration is stepwise, via !" # and an electron transport chain. ellular respiration does not oxidi'e glucose in a single step that transfers all the hydrogen in the fuel to oxygen at one time. #ather, glucose and other fuels are %roken do"n in a series of steps, each cataly'ed %y a specific en'yme. !t key steps, electrons are stripped from the glucose. In many oxidation reactions, the electron is transferred "ith a proton, as a hydrogen atom. The hydrogen atoms are not transferred directly to oxygen %ut are passed first to a coen'yme called '()* (nicotinamide adenine dinucleotide). !s an electron acceptor, 5!?- functions as an oxidi'ing agent during respiration. /o" does 5!?- trap electrons from glucose@ o ?ehydrogenase en'ymes strip t"o hydrogen atoms from the su%strate (glucose), thus oxidi'ing it. o The en'yme passes t"o electrons and one proton to 5!?-. o The other proton is released as /- to the surrounding solution.

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Ay receiving t"o electrons and only one proton, 5!? - has its charge neutrali'ed "hen it is reduced to 5!?/. o 5!?- functions as the oxidi'ing agent in many of the redox steps during the %reakdo"n of glucose. The electrons carried %y 5!?/ lose very little of their potential energy in this process. Each 5!?/ molecule formed during respiration represents stored energy. This energy is tapped to synthesi'e !TP as electrons ;fall< do"n an energy gradient from 5!?/ to oxygen. /o" are electrons extracted from glucose and stored in 5!?/ finally transferred to oxygen@ Bnlike the explosive release of heat energy that occurs "hen / . and *. are com%ined ("ith a spark for activation energy), cellular respiration uses an electron transport chain to %reak the fall of electrons to *. into several steps. The electron transport chain consists of several molecules (primarily proteins) %uilt into the inner mem%rane of a mitochondrion of eukaryotic cells and the plasma mem%rane of aero%ically respiring prokaryotes. Electrons released from food are shuttled %y 5!?/ to the ;top< higher4energy end of the chain. !t the ;%ottom< lo"er4energy end, oxygen captures the electrons along "ith / - to form "ater. Electron transfer from 5!?/ to oxygen is an exergonic reaction "ith a free4energy change of CD kcalEmol. Electrons are passed to increasingly electronegative molecules in the chain until they reduce oxygen, the most electronegative receptor. Each ;do"nhill< carrier is more electronegative than, and thus capa%le of oxidi'ing, its ;uphill< neigh%or, "ith oxygen at the %ottom of the chain. The electrons removed from glucose %y 5!? - fall do"n an energy gradient in the electron transport chain to a far more sta%le location in the electronegative oxygen atom. In summary, during cellular respiration, most electrons travel the follo"ing ;do"nhill< route$ glucose 5!?/ electron transport chain oxygen. #espiration occurs in three meta%olic stages$ glycolysis, the citric acid cycle, and the electron transport chain and oxidative phosphorylation. +lycolysis occurs in the cytosol. It %egins cata%olism %y %reaking glucose into t"o molecules of pyruvate. The citric aci# cycle occurs in the mitochondrial matrix of eukaryotic cells or in the cytoplasm of prokaryotes. It completes the %reakdo"n of glucose %y oxidi'ing a derivative of pyruvate to car%on dioxide. (everal steps in glycolysis and the citric acid cycle are redox reactions in "hich dehydrogenase en'ymes transfer electrons from su%strates to 5!? -, forming 5!?/. In the third stage of respiration, the electron transport chain accepts electrons from the %reakdo"n products of the first t"o stages (most often via 5!?/). In the electron transport chain, the electrons move from molecule to molecule until they com%ine "ith molecular oxygen and hydrogen ions to form "ater.
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The stages of cellular respiration$ a preview.

Lecture Outline for Campbell/Reece Biology, 8th Edition, Pearson Education, Inc.

!s the electrons are passed along the chain, the energy released at each step in the chain is stored in a form the mitochondrion (or prokaryotic cell) can use to make !TP. This mode of !TP synthesis is called o$i#ative phosphorylation %ecause it is po"ered %y the redox reactions of the electron transport chain. In eukaryotic cells, the inner mem%rane of the mitochondrion is the site of electron transport and chemiosmosis, the processes that together constitute oxidative phosphorylation. In prokaryotes, these processes take place in the plasma mem%rane. *xidative phosphorylation produces almost F6G of the !TP generated %y respiration. (ome !TP is also formed directly during glycolysis and the citric acid cycle %y su"strate, level phosphorylation, in "hich an en'yme transfers a phosphate group from an organic su%strate molecule to !?P, forming !TP. ,or each molecule of glucose degraded to car%on dioxide and "ater %y respiration, the cell makes as many as D3 !TP, each "ith =.D kcalEmol of free energy. #espiration uses the small steps in the respiratory path"ay to %reak the large denomination of energy contained in glucose into the small change of !TP. o The quantity of energy in !TP is more appropriate for the energy level of "ork required in the cell.

Concept 9 - +lycolysis harvests chemical energy "y o$i#i%ing glucose to pyruvate

?uring glycolysis, glucose, a six4car%on sugar, is split into t"o three4car%on sugars. These smaller sugars are then oxidi'ed and rearranged to form t"o molecules of pyruvate, the ioni'ed form of pyruvic acid. Each of the ten steps in glycolysis is cataly'ed %y a specific en'yme. These steps can %e divided into t"o phases. 1. In the energy investment phase, the cell spends !TP. .. In the energy payoff phase, this investment is repaid "ith interest. !TP is produced %y su%strate4level phosphorylation, and 5!?- is reduced to 5!?/ %y electrons released %y the oxidation of glucose. The net yield from glycolysis is . !TP and . 5!?/ per glucose. o 5o *. is produced during glycolysis. Hlycolysis can occur "hether or not *. is present. If *. is present, the chemical energy stored in pyruvate and 5!?/ can %e extracted %y the citric acid cycle and oxidative phosphorylation.

Concept 9 . /he citric aci# cycle completes the energy,yiel#ing o$i#ation of organic molecules
+ore than three4quarters of the original energy in glucose is still present in the t"o molecules of pyruvate. If molecular oxygen is present in eukaryotic cells, pyruvate enters the mitochondrion, "here en'ymes of the citric acid cycle complete the oxidation of the organic fuel to car%on dioxide.
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Lecture Outline for Campbell/Reece Biology, 8th Edition, Pearson Education, Inc.

In prokaryotic cells, this process occurs in the cytoplasm.

!fter pyruvate enters the mitochondrion via active transport, it is converted to a compound called acetyl coen'yme !, or acetyl Co(. This step, the &unction %et"een glycolysis and the citric acid cycle, is accomplished %y a multien'yme complex that cataly'es three reactions. 1. ! car%oxyl group is removed as *.. The car%on dioxide is fully oxidi'ed and thus has little chemical energy. 2. The remaining t"o4car%on fragment is oxidi'ed to form acetate. !n en'yme transfers the pair of electrons to 5!? - to form 5!?/. 3. !cetate com%ines "ith coen'yme ! to form the very reactive molecule acetyl o!. ?ue to the chemical nature of the o! group, a sulfur4containing compound derived from a A vitamin, acetyl o! has a high potential energy. o In other "ords, the reaction of acetyl o! to yield lo"er4energy products is highly exergonic. !cetyl o! is no" ready to feed its acetyl group into the citric acid cycle for further oxidation. The citric acid cycle is also called the tricar%oxylic acid cycle or the Ire%s cycle. o The latter name honors /ans Ire%s, "ho "as largely responsi%le for elucidating the cycleJs path"ays in the 1FD6s. The citric acid cycle oxidi'es organic fuel derived from pyruvate. Three *. molecules are released, including the one released during the conversion of pyruvate to acetyl o!. The cycle generates one !TP per turn %y su%strate4level phosphorylation. +ost of the chemical energy is transferred to 5!? - and a related electron carrier, the coen'yme ,!?, during the redox reactions. The reduced coen'ymes, 5!?/ and ,!?/., transfer high4energy electrons to the electron transport chain. The citric acid cycle has eight steps, each cataly'ed %y a specific en'yme. o The acetyl group of acetyl o! &oins the cycle %y com%ining "ith the compound oxaloacetate, forming citrate. o The next seven steps decompose the citrate %ack to oxaloacetate. o It is the regeneration of oxaloacetate that makes this process a cycle. ,or each acetyl group that enters the cycle, D 5!? - are reduced to 5!?/. In one step, electrons are transferred to ,!? instead of 5!? -. Then ,!? accepts . electrons and . protons to %ecome ,!?/ .. In the cells of plants, %acteria, and a fe" animal tissues, the citric acid cycle forms an !TP molecule %y su%strate4level phosphorylation. In most animal tissue cells, guanosine triphosphate (HTP) is formed %y the same process of su%strate4level phosphorylation. HTP may %e used to synthesi'e an !TP or to directly po"er "ork in the cell. The output from this step is the only !TP generated directly %y the citric acid cycle.
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Lecture Outline for Campbell/Reece Biology, 8th Edition, Pearson Education, Inc.

+ost of the !TP produced %y respiration results from oxidative phosphorylation, as the 5!?/ and ,!?/. produced %y the citric acid cycle relay the electrons extracted from food to the electron transport chain. This process supplies the necessary energy for the phosphorylation of !?P to !TP.

Concept 9 0 )uring o$i#ative phosphorylation& chemiosmosis couples electron transport to (/1 synthesis
*nly K of D3 !TP ultimately produced %y the respiration of glucose are produced %y su%strate4level phosphorylation. o T"o !TP are produced during glycolysis, and . !TP are produced during the citric acid cycle. 5!?/ and ,!?/. account for most of the energy extracted from glucose. These reduced coen'ymes link glycolysis and the citric acid cycle to oxidative phosphorylation, "hich uses energy released %y the electron transport chain to po"er !TP synthesis. The electron transport chain is a collection of molecules em%edded in the cristae, the folded inner mem%rane of the mitochondrion. o In prokaryotes, the electron transport chain is located in the plasma mem%rane. The folding of the inner mem%rane to form cristae increases its surface area, providing space for thousands of copies of the chain in each mitochondrion. +ost components of the chain are proteins that exist in multiprotein complexes num%ered IL IM. Tightly %ound to these proteins are prosthetic groups, nonprotein components essential for catalysis. Electrons drop in free energy as they pass do"n the electron transport chain. ?uring electron transport along the chain, electron carriers alternate %et"een reduced and oxidi'ed states as they accept and donate electrons. o Each component of the chain %ecomes reduced "hen it accepts electrons from its ;uphill< neigh%or, "hich is less electronegative. o It then returns to its oxidi'ed form as it passes electrons to its more electronegative ;do"nhill< neigh%or. Electrons carried %y 5!?/ are transferred to the first molecule in the electron transport chain, a flavoprotein. In the next redox reaction, the flavoprotein returns to its oxidi'ed form as it passes electrons to an iron4sulfur protein. The iron4sulfur protein then passes the electrons to a compound called u%iquinone, a small hydropho%ic molecule and the only mem%er of the electron transport chain that is not a protein. +ost of the remaining electron carriers %et"een u%iquinone and oxygen are proteins called cytochromes o The prosthetic group of each cytochrome is a heme group "ith an iron atom that accepts and donates electrons.

The inner mitochondrial mem%rane couples electron transport to !T& synthesis.

Lecture Outline for Campbell/Reece Biology, 8th Edition, Pearson Education, Inc.

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The last cytochrome of the chain, cyt aD, passes its electrons to oxygen, "hich is very electronegative. Each oxygen atom also picks up a pair of hydrogen ions from the aqueous solution to form "ater. The electrons carried %y ,!?/. have lo"er free energy and are added at a lo"er energy level than those carried %y 5!?/. o The electron transport chain provides a%out one4third less energy for !TP synthesis "hen the electron donor is ,!?/. rather than 5!?/. The electron transport chain generates no !TP directly. Its function is to %reak the large free4energy drop from food to oxygen into a series of smaller steps that release energy in managea%le amounts. 'hemiosmosis couples electron transport and energy release to !T& synthesis. ! protein complex in the cristae, (/1 synthase, actually makes !TP from !?P and Pi. !TP synthase "orks like an ion pump running in reverse. o Ion pumps usually use !TP as an energy source to transport ions against their gradients. o En'ymes can cataly'e a reaction in either direction, depending on the G for the reaction, "hich is affected %y the local concentrations of reactants and products. o #ather than hydroly'ing !TP to pump protons against their concentration gradient, under the conditions of cellular respiration, !TP synthase uses the energy of an existing ion gradient to po"er !TP synthesis. The po"er source for the !TP synthase is a difference in the concentrations of / - on opposite sides of the inner mitochondrial mem%rane. o This is also a p/ gradient. This process, in "hich energy stored in the form of a hydrogen ion gradient across a mem%rane is used to drive cellular "ork such as the synthesis of !TP, is called chemiosmosis. o /ere, osmosis refers to the flo" of /- across a mem%rane. ,rom studying the structure of !TP synthase, scientists have learned ho" the flo" of / through this large en'yme po"ers !TP generation. !TP synthase is a multisu%unit complex "ith four main parts, each made up of multiple polypeptides. Protons move one %y one into %inding sites on one of the parts (the rotor), causing it to spin in a "ay that cataly'es !TP production from !?P and inorganic phosphate. o !TP synthase is the smallest molecular rotary motor kno"n in nature. Part of the complex actually spins around in the mem%rane "hen the reaction proceeds in the direction of !TP hydrolysis. Aiochemists assumed that the same rotational mechanism "as responsi%le for !TP synthesis, %ut they lacked experimental evidence. In .66K, nanotechnology techniques (involving control of matter on the molecular scale) "ere used to demonstrate that the direction of rotation of one part of the complex in relation to another is solely responsi%le for either !TP synthesis or !TP hydrolysis %y this en'yme. /o" does the inner mitochondrial mem%rane or the prokaryotic plasma mem%rane generate and maintain the /- gradient that drives !TP synthesis in the !TP synthase protein complex@

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o o o

Esta%lishing the /- gradient is the function of the electron transport chain. The chain is an energy converter that uses the exergonic flo" of electrons to pump / across the mem%rane from the mitochondrial matrix into the intermem%rane space. The /- has a tendency to diffuse do"n its gradient.

The !TP synthase molecules are the only place "here /- can diffuse %ack to the matrix. The exergonic flo" of /- is used %y the en'yme to generate !TP. This coupling of the redox reactions of the electron transport chain to !TP synthesis is an example of chemiosmosis. /o" does the electron transport chain pump protons@ o ertain mem%ers of the electron transport chain accept and release / - along "ith electrons. o !t certain steps along the chain, electron transfers cause / - to %e taken up and released into the surrounding solution. o o o The electron carriers are spatially arranged in the mem%rane in such a "ay that protons are accepted from the mitochondrial matrix and deposited in the intermem%rane space. The /- gradient that results is the proton,motive force, a gradient "ith the capacity to do "ork. The force drives /- %ack across the mem%rane through the specific / - channels provided %y !TP synthases.

Chemiosmosis is an energy-coupling mechanism that uses energy stored in the form of an H + gradient across a membrane to drive cellular work. In mitochondria, the energy for proton gradient formation comes from exergonic redox reactions, and !TP synthesis is the "ork performed. hemiosmosis in chloroplasts also generates !TP, %ut light drives the electron flo" do"n an electron transport chain and /- gradient formation. Prokaryotes generate /- gradients across their plasma mem%rane. Prokaryotes use the proton4motive force not only to generate !TP %ut also to pump nutrients and "aste products across the mem%rane and to rotate their flagella. ?uring cellular respiration, most energy flo"s as follo"s$ glucose 5!?/ electron transport chain proton4motive force !TP. NetJs consider the products generated "hen cellular respiration oxidi'es a molecule of glucose to six molecules of *.. ,our !TP molecules are produced %y su%strate4level phosphorylation during glycolysis and the citric acid cycle. +any more !TP molecules are generated %y oxidative phosphorylation. Each 5!?/ from the citric acid cycle and the conversion of pyruvate contri%utes enough energy to the proton4motive force to generate a maximum of D !TP. There are three reasons "e cannot state an exact num%er of !TP molecules generated %y one molecule of glucose. 1. Phosphorylation and the redox reactions are not directly coupled to each other, so the ratio of the num%er of 5!?/ to the num%er of !TP is not a "hole num%er.
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(ere is an accounting of !T& production %y cellular respiration.

Lecture Outline for Campbell/Reece Biology, 8th Edition, Pearson Education, Inc.

*ne 5!?/ results in 16 /- %eing transported across the inner mitochondrial mem%rane. Aet"een D and K /- must reenter the mitochondrial matrix via !TP synthase to generate 1 !TP. Therefore, 1 5!?/ generates enough proton4motive force for the synthesis of ..CL D.D !TP. :e round off and say that 1 5!?/ generates D !TP. The citric acid cycle also supplies electrons to the electron transport chain via ,!?/., %ut %ecause it enters later in the chain, each molecule of this electron carrier is responsi%le for the transport of only enough / - for the synthesis of 1.CL. !TP. There is also a slight energetic cost of moving the !TP formed in the mitochondrion out into the eukaryotic cytoplasm "here it "ill %e used. 2. The !TP yield varies slightly depending on the type of shuttle used to transport electrons from the cytosol into the mitochondrion. The mitochondrial inner mem%rane is impermea%le to 5!?/, so the t"o electrons of the 5!?/ produced in glycolysis must %e conveyed into the mitochondrion %y one of several electron shuttle systems. In some shuttle systems, the electrons are passed to 5!? -, "hich generates D !TP. In others, the electrons are passed to ,!?, "hich generates only . !TP. 3. The proton4motive force generated %y the redox reactions of respiration may drive other kinds of "ork, such as mitochondrial uptake of pyruvate from the cytosol. If all the proton4motive force generated %y the electron transport chain "ere used to drive !TP synthesis, one glucose molecule could generate a maximum of DK !TP %y oxidative phosphorylation plus K !TP (net) from su%strate4level phosphorylation to give a total yield of D0LD3 !TP (depending on the efficiency of the shuttle). /o" efficient is respiration in generating !TP@ o omplete oxidation of glucose releases 030 kcalEmol. o Phosphorylation of !?P to form !TP requires at least =.D kcalEmol. o Efficiency of respiration is =.D kcalEmol times D3 !TPEglucose divided %y 030 kcalEmol glucose, "hich equals 6.K, or K6G. o !pproximately 06G of the energy from glucose is lost as heat. o (ome of that heat is used to maintain our high %ody temperature (D=O ). ellular respiration is remarka%ly efficient in energy conversion. o ,or example, the most efficient automo%ile converts only a%out .CG of the energy stored in gasoline to energy that moves the car.

Concept 9 2 3ermentation an# anaero"ic respiration ena"le some cells to pro#uce (/1 without the use of o$ygen
:ithout electronegative oxygen to pull electrons do"n the transport chain, oxidative phosphorylation ceases. /o"ever, there are t"o general mechanisms %y "hich certain cells can oxidi'e organic fuel and generate !TP without the use of oxygen$ fermentation and anaero%ic respiration. o !n electron transport chain is present in aero%ic respiration %ut not in fermentation. !naero%ic respiration takes place in organisms that have an electron transport chain %ut do
9 !(

Lecture Outline for Campbell/Reece Biology, 8th Edition, Pearson Education, Inc.

not use oxygen as a final electron acceptor at the end of the chain. o (ome ;sulfate4reducing< marine %acteria, for instance, use the electronegative sulfate ion ((*K.4) at the end of their respiratory chain. o *peration of the chain %uilds up a proton4motive force used to produce !TP, %ut / .( (hydrogen sulfide) is produced as a %y4product rather than / .* ("ater). ,ermentation provides a mechanism %y "hich some cells can oxidi'e organic fuel and generate !TP "ithout the use of oxygen or any electron transport chain (that is, "ithout cellular respiration). o In glycolysis, glucose is oxidi'ed to t"o pyruvate molecules "ith 5!? - as the oxidi'ing agent. o Hlycolysis is exergonic and produces . !TP (net) %y su%strate4level phosphorylation. If oxygen is present, additional !TP can %e generated "hen 5!?/ delivers its electrons to the electron transport chain. /o"ever, glycolysis generates . !TP "hether oxygen is present 4aero"ic5 or not 4anaero"ic5. ,ermentation can generate !TP from glucose %y su%strate4level phosphorylation as long as there is a supply of 5!?- to accept electrons during the oxidation step of glycolysis. o If the 5!?- pool is exhausted, glycolysis shuts do"n. Bnder aero%ic conditions, 5!?/ transfers its electrons to the electron transfer chain, recycling 5!?-. )ermentation pathways recycle !"# %y transferring electrons from !"( to pyruvate or derivatives of pyruvate. In alcohol fermentation, pyruvate is converted to ethanol in t"o steps. 1. Pyruvate is converted to a t"o4car%on compound, acetaldehyde, %y the removal of * .. .. !cetaldehyde is reduced %y 5!?/ to ethanol. This process regenerates the supply of 5!? - needed for the continuation of glycolysis. o !lcohol fermentation %y yeast is used in %re"ing, %aking, and "inemaking. ?uring lactic aci# fermentation, pyruvate is reduced directly %y 5!?/ to form lactate (the ioni'ed form of lactic acid) "ithout the release of * .. o Nactic acid fermentation %y some fungi and %acteria is used to make cheese and yogurt. /uman muscle cells s"itch from aero%ic respiration to lactic acid fermentation to generate !TP "hen *. is scarce. This may occur in the early stages of strenuous exercise. o The "aste product, lactate, "as previously thought to cause muscle fatigue and pain, %ut recent research suggests instead that increased levels of potassium ions (I -) may %e to %lame) lactate appears to enhance muscle performance. o Excess lactate is gradually carried a"ay %y the %lood to the liver, "here it is converted %ack to pyruvate %y liver cells. )ermentation and cellular respiration are compared. ,ermentation and cellular respiration are anaero%ic and aero%ic alternatives, respectively, for producing !TP from sugars. o Aoth use glycolysis to oxidi'e sugars to pyruvate "ith a net production of . !TP %y su%strate4level phosphorylation. o Aoth use 5!?- as an oxidi'ing agent to accept electrons from food during glycolysis.

Lecture Outline for Campbell/Reece Biology, 8th Edition, Pearson Education, Inc.

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The t"o processes differ in their mechanism for oxidi'ing 5!?/ to 5!? -, "hich is required to sustain glycolysis. o In fermentation, the electrons of 5!?/ are passed to an organic molecule such as pyruvate (lactic acid fermentation) or acetaldehyde (alcohol fermentation), in order to regenerate 5!?-. o In cellular respiration, the electrons of 5!?/ are ultimately passed to * ., generating !TP %y oxidative phosphorylation. +ore !TP is generated from the oxidation of pyruvate in the citric acid cycle. o :ithout oxygen, the energy still stored in pyruvate is unavaila%le to the cell. o Bnder aero%ic respiration, a molecule of glucose yields D3 !TP, %ut the same molecule of glucose yields only . !TP under anaero%ic respiration. Organisms vary in the pathways availa%le to them to %rea* down sugars. O"ligate anaero"es carry out only fermentation or anaero%ic respiration and cannot survive in the presence of oxygen. ! fe" cell types, such as the cells of the verte%rate %rain, can carry out only aero%ic oxidation of pyruvate, not fermentation. 8east and many %acteria are facultative anaero"es that can survive using either fermentation or respiration. o !t a cellular level, human muscle cells can %ehave as facultative anaero%es. ,or facultative anaero%es, pyruvate is a fork in the meta%olic road that leads to t"o alternative routes. o Bnder aero%ic conditions, pyruvate is converted to acetyl o! and oxidation continues in the citric acid cycle. o Bnder anaero%ic conditions, pyruvate serves as an electron acceptor to recycle 5!? -. To make the same amount of !TP, a facultative anaero%e must consume sugar at a much faster rate "hen fermenting than "hen respiring. The role of glycolysis in %oth fermentation and respiration has an evolutionary %asis. !ncient prokaryotes used glycolysis to make !TP long %efore oxygen "as present in EarthJs atmosphere. The oldest %acterial fossils are more than D.C %illion years old, appearing long %efore apprecia%le quantities of *. accumulated in the atmosphere a%out ..= %illion years ago. o yano%acteria produced this *. as a %y4product of photosynthesis. The first prokaryotes may have generated !TP exclusively from glycolysis, "hich does not require oxygen. The fact that glycolysis is a u%iquitous meta%olic path"ay and occurs in the cytosol "ithout mem%rane4enclosed organelles suggests that this path"ay evolved very early in the history of life on Earth.

Concept 9 6 +lycolysis an# the citric aci# cycle connect to many other meta"olic pathways
Hlycolysis and the citric acid cycle are ma&or intersections of various cata%olic and ana%olic (%iosynthetic) path"ays.
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Lecture Outline for Campbell/Reece Biology, 8th Edition, Pearson Education, Inc.

! variety of organic molecules can %e used to ma*e !T&. Hlycolysis can accept a "ide range of car%ohydrates for cata%olism. o Polysaccharides like starch or glycogen can %e hydroly'ed to glucose monomers that enter glycolysis and the citric acid cycle. o The digestion of disaccharides, including sucrose, provides glucose and other monosaccharides as fuel for respiration. The other t"o ma&or fuels, proteins and fats, can also enter the respiratory path"ays used %y car%ohydrates. Proteins must first %e digested to individual amino acids. o +any of the amino acids are used %y the organism to %uild ne" proteins. o !mino acids that "ill %e cata%oli'ed must have their amino groups removed via deamination. o The nitrogenous "aste is excreted as ammonia, urea, or another "aste product. o The car%on skeletons are modified %y en'ymes and enter as intermediaries into glycolysis or the citric acid cycle, depending on their structure. ata%olism can also harvest energy stored in fats o%tained from food or from storage cells in the %ody. ,ats must %e digested to glycerol and fatty acids. o Hlycerol can %e converted to glyceraldehyde phosphate, an intermediate of glycolysis. The rich energy of fatty acids is accessed as fatty acids are split into t"o4car%on fragments via "eta o$i#ation. These molecules enter the citric acid cycle as acetyl o!. 5!?/ and ,!?/. are also generated during %eta oxidation) they can enter the electron transport chain, leading to further !TP production. ! gram of fat oxidi'ed %y respiration generates t"ice as much !TP as a gram of car%ohydrate. The meta%olic pathways of respiration also play a role in ana%olic pathways of the cell. In addition to calories, food must provide the car%on skeletons that cells require to make their o"n molecules. (ome organic monomers o%tained from digestion can %e used directly. Intermediaries in glycolysis and the citric acid cycle can %e diverted to ana%olic path"ays as precursors from "hich the cell can synthesi'e the molecules it requires. o ,or example, a human cell can synthesi'e a%out half the .6 different amino acids %y modifying compounds from the citric acid cycle. The rest are ;essential amino acids< that must %e o%tained in the diet. o Hlucose can %e synthesi'ed from pyruvate) fatty acids can %e synthesi'ed from acetyl o!. !na%olic, or %iosynthetic, path"ays do not generate !TP %ut instead consume it. Hlycolysis and the citric acid cycle function as meta%olic interchanges that ena%le cells to convert one kind of molecule to another as needed. o ,or example, excess car%ohydrates and proteins can %e converted to fats through intermediaries of glycolysis and the citric acid cycle.

Lecture Outline for Campbell/Reece Biology, 8th Edition, Pearson Education, Inc.

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If "e eat more food than "e need, "e store fat even if our diet is fat4free.

+eta%olism is remarka%ly versatile and adapta%le. Aasic principles of supply and demand regulate the meta%olic economy. If a cell has an excess of a certain amino acid, it typically uses feed%ack inhi%ition to prevent the diversion of intermediary molecules from the citric acid cycle to the synthesis path"ay of that amino acid. The rate of cata%olism is also regulated, typically %y the level of !TP in the cell. o If !TP levels drop, cata%olism speeds up to produce more !TP. o :hen there is plenty of !TP to meet demand, respiration slo"s do"n, sparing valua%le organic molecules for other functions. ontrol of cata%olism is %ased mainly on regulating the activity of en'ymes at strategic points in the cata%olic path"ay. *ne strategic point occurs in the third step of glycolysis, cataly'ed %y phosphofructokinase, an en'yme that functions as the pacemaker of respiration. Phosphofructokinase cataly'es the earliest step that irreversi%ly commits the su%strate to glycolysis. Phosphofructokinase is an allosteric en'yme "ith receptor sites for specific inhi%itors and activators. Phosphofructokinase is inhi%ited %y !TP and stimulated %y !+P (derived from !?P). o :hen !TP levels are high, inhi%ition of this en'yme slo"s glycolysis. o !s !TP levels drop and !?P and !+P levels rise, the en'yme %ecomes active again and glycolysis speeds up. itrate, the first product of the citric acid cycle, is also an inhi%itor of phosphofructokinase. o This synchroni'es the rate of glycolysis and the citric acid cycle. If intermediaries from the citric acid cycle are diverted to other uses (for example, amino acid synthesis), glycolysis speeds up to replace these molecules. +eta%olic %alance is augmented %y the control of other en'ymes at other key locations in glycolysis and the citric acid cycle. ells are thrifty, expedient, and responsive in their meta%olism. ellular respiration functions in the %road context of energy flo" and chemical cycling in ecosystems. The energy that keeps us alive is released, not produced, %y cellular respiration.

)eed%ac* mechanisms control cellular respiration.

Lecture Outline for Campbell/Reece Biology, 8th Edition, Pearson Education, Inc.

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