If the electron acceptor is oxygen, the process is more specifically known as aerobic cellular respiration. If the electron acceptor is a molecule other than oxygen, this is anaerobic cellular respiration.Fermentation, which is also an anaerobic process, is not respiration, as no external electron acceptor is involved.[2]
The reactions involved in respiration arecatabolic reactions, which break large molecules into smaller ones, producing large amounts of energy (ATP). Respiration is one of the key ways a cell releases chemical energy to fuel cellular activity. The overall reaction occurs in a series of biochemical steps, some of which areredox reactions. Although cellular respiration is technically acombustion reaction, it is an unusual one because of the slow, controlled release of energy from the series of reactions.
Nutrients that are commonly used by animal and plant cells in respiration includesugar,amino acids andfatty acids, and the most commonoxidizing agent is molecularoxygen (O2). The chemical energy stored in ATP (the bond of its third phosphate group to the rest of the molecule can be broken allowing more stable products to form, thereby releasing energy for use by the cell) can then be used to drive processes requiring energy, includingbiosynthesis,locomotion or transportation of molecules acrosscell membranes.
C6H12O6 (s) + 6 O2 (g) → 6 CO2 (g) + 6 H2O (l) + energy
ΔG = −2880 kJ per mol of C6H12O6
The negative ΔG indicates that the reaction isexothermic (exergonic) and can occur spontaneously.[3]
The potential of NADH and FADH2 is converted to more ATP through anelectron transport chain with oxygen and protons (hydrogen ions) as the "terminal electron acceptors". Most of the ATP produced by aerobic cellular respiration is made byoxidative phosphorylation. The energy released is used to create achemiosmotic potential by pumpingprotons across a membrane. This potential is then used to driveATP synthase and produce ATP fromADP and a phosphate group. Biology textbooks often state that 38 ATP molecules can be made per oxidized glucose molecule during cellular respiration (2 from glycolysis, 2 from theKrebs cycle, and about 34 from the electron transport system).[4] However, this maximum yield is never quite reached because of losses due toleaky membranes as well as the cost of moving pyruvate and ADP into the mitochondrial matrix, and current estimates range around 29 to 30 ATP per glucose.[4]
Aerobic metabolism is up to 15 times more efficient than anaerobic metabolism (which yields 2 molecules of ATP per 1 molecule of glucose). However, some anaerobic organisms, such asmethanogens are able to continue withanaerobic respiration, yielding more ATP by using inorganic molecules other than oxygen as final electron acceptors in the electron transport chain. They share the initial pathway ofglycolysis but aerobic metabolism continues with the Krebs cycle and oxidative phosphorylation. The post-glycolytic reactions take place in the mitochondria ineukaryotic cells, and in thecytoplasm inprokaryotic cells.[5]
Out of the cytoplasm it goes into the Krebs cycle with the acetyl CoA. It then mixes with CO2 and makes 2 ATP, NADH, and FADH. From there the NADH and FADH go into the NADH reductase, which produces the enzyme. The NADH pulls the enzyme's electrons to send through the electron transport chain. The electron transport chain pulls H+ ions through the chain. From the electron transport chain, the released hydrogen ions make ADP for an result of 32 ATP. Lastly, ATP leaves through the ATP channel and out of the mitochondria.
Glycolysis is ametabolic pathway that takes place in thecytosol of cells in all living organisms. Glycolysis can be literally translated as "sugar splitting",[8] and occurs regardless of oxygen's presence or absence. The process converts one molecule ofglucose into two molecules ofpyruvate (pyruvic acid), generating energy in the form of two net molecules ofATP. Four molecules of ATP per glucose are actually produced, but two are consumed as part of thepreparatory phase. The initialphosphorylation of glucose is required to increase the reactivity (decrease its stability) in order for the molecule to be cleaved into twopyruvate molecules by the enzymealdolase. During thepay-off phase of glycolysis, fourphosphate groups are transferred to four ADP bysubstrate-level phosphorylation to make four ATP, and two NADH are also produced during the pay-off phase. The overall reaction can be expressed this way:[9]
Glucose + 2 NAD+ + 2 Pi + 2 ADP → 2pyruvate + 2 NADH + 2 ATP + 2 H+ + 2 H2O + energy
Starting with glucose, 1 ATP is used to donate a phosphate to glucose to produceglucose 6-phosphate. Glycogen can be converted into glucose 6-phosphate as well with the help ofglycogen phosphorylase. During energy metabolism, glucose 6-phosphate becomesfructose 6-phosphate. An additional ATP is used to phosphorylate fructose 6-phosphate intofructose 1,6-bisphosphate by the help ofphosphofructokinase. Fructose 1,6-biphosphate then splits into two phosphorylated molecules with three carbon chains which later degrades into pyruvate.[7]: 88–90
Pyruvate is oxidized toacetyl-CoA and CO2 by thepyruvate dehydrogenase complex (PDC). The PDC contains multiple copies of three enzymes and is located in themitochondria of eukaryotic cells and in thecytosol of prokaryotes. In the conversion of pyruvate to acetyl-CoA, one molecule of NADH and one molecule of CO2 is formed.[10]
Thecitric acid cycle is also called theKrebs cycle or thetricarboxylic acid cycle. When oxygen is present,acetyl-CoA is produced from the pyruvate molecules created from glycolysis. Onceacetyl-CoA is formed, aerobic or anaerobic respiration can occur. When oxygen is present, the mitochondria will undergo aerobic respiration which leads to the Krebs cycle. However, if oxygen is not present,fermentation of the pyruvate molecule will occur. In the presence of oxygen, when acetyl-CoA is produced, the molecule then enters the citric acid cycle (Krebs cycle) inside the mitochondrial matrix, and is oxidized toCO2 while at the same time reducingNAD toNADH. NADH can be used by theelectron transport chain to create furtherATP as part of oxidative phosphorylation. To fully oxidize the equivalent of one glucose molecule, two acetyl-CoA must be metabolized by the Krebs cycle. Two low-energywaste products, H2O and CO2, are created during this cycle.[11][12]
The citric acid cycle is an 8-step process involving 18 different enzymes and co-enzymes. During the cycle, acetyl-CoA (2 carbons) +oxaloacetate (4 carbons) yieldscitrate (6 carbons), which is rearranged to a more reactive form calledisocitrate (6 carbons). Isocitrate is modified to becomeα-ketoglutarate (5 carbons),succinyl-CoA,succinate,fumarate,malate and, finally,oxaloacetate.[13]
The net gain from one cycle is 3 NADH and 1 FADH2 as hydrogen (proton plus electron) carrying compounds and 1 high-energyGTP, which may subsequently be used to produce ATP. Thus, the total yield from 1 glucose molecule (2 pyruvate molecules) is 6 NADH, 2 FADH2, and 2 ATP.[11][12][7]: 90–91
In eukaryotes, oxidative phosphorylation occurs in the mitochondrialcristae. It comprises the electron transport chain that establishes aproton gradient (chemiosmotic potential) across the boundary of the inner membrane by oxidizing the NADH produced from the Krebs cycle. ATP is synthesized by the ATP synthase enzyme when the chemiosmotic gradient is used to drive the phosphorylation of ADP. The electrons are finally transferred toexogenous oxygen and, with the addition of two protons, water is formed.[14]
The table below describes the reactions involved when one glucose molecule is fully oxidized into carbon dioxide. It is assumed that all thereducedcoenzymes are oxidized by the electron transport chain and used for oxidative phosphorylation.
Step
coenzyme yield
ATP yield
Source of ATP
Glycolysis preparatory phase
−2
Phosphorylation of glucose and fructose 6-phosphate uses two ATP from the cytoplasm.
Glycolysis pay-off phase
4
Substrate-level phosphorylation
2 NADH
3 or 5
Oxidative phosphorylation: Each NADH produces net 1.5 ATP (instead of usual 2.5) due to NADH transport over the mitochondrial membrane
Oxidative decarboxylation of pyruvate
2 NADH
5
Oxidative phosphorylation
Krebs cycle
2
Substrate-level phosphorylation
6 NADH
15
Oxidative phosphorylation
2 FADH2
3
Oxidative phosphorylation
Total yield
30 or 32 ATP
From the complete oxidation of one glucose molecule to carbon dioxide and oxidation of all the reduced coenzymes.
Although there is a theoretical yield of 38 ATP molecules per glucose during cellular respiration, such conditions are generally not realized because of losses such as the cost of moving pyruvate (from glycolysis), phosphate, and ADP (substrates for ATP synthesis) into the mitochondria. All are actively transported using carriers that utilize the stored energy in the protonelectrochemical gradient.
Pyruvate is taken up by a specific, lowKm transporter to bring it into the mitochondrial matrix for oxidation by the pyruvate dehydrogenase complex.
Thephosphate carrier (PiC) mediates the electroneutral exchange (antiport) of phosphate (H2PO−4; Pi) for OH− orsymport of phosphate and protons (H+) across the inner membrane, and the driving force for moving phosphate ions into the mitochondria is theproton motive force.
TheATP-ADP translocase (also calledadenine nucleotide translocase, ANT) is anantiporter and exchanges ADP and ATP across theinner membrane. The driving force is due to the ATP (−4) having a more negative charge than the ADP (−3), and thus it dissipates some of the electrical component of the proton electrochemical gradient.
The outcome of these transport processes using the proton electrochemical gradient is that more than 3 H+ are needed to make 1 ATP. Obviously, this reduces the theoretical efficiency of the whole process and the likely maximum is closer to 28–30 ATP molecules.[4] In practice the efficiency may be even lower because the inner membrane of the mitochondria is slightly leaky to protons.[15] Other factors may also dissipate the proton gradient creating an apparently leaky mitochondria. An uncoupling protein known asthermogenin is expressed in some cell types and is a channel that can transport protons. When this protein is active in the inner membrane it short circuits the coupling between theelectron transport chain andATP synthesis. The potential energy from the proton gradient is not used to make ATP but generates heat. This is particularly important inbrown fat thermogenesis of newborn and hibernating mammals.
According to some newer sources, the ATP yield during aerobic respiration is not 36–38, but only about 30–32 ATP molecules / 1 molecule of glucose[16], because:
ATP synthase produces 1 ATP / 3 H+. However the exchange of matrix ATP for cytosolic ADP and Pi (antiport with OH− or symport with H+) mediated byATP–ADP translocase andphosphate carrier consumes 1 H+ / 1 ATP as a result of regeneration of the transmembrane potential changed during this transfer, so the net ratio is 1 ATP : 4 H+.
The mitochondrialelectron transport chainproton pump transfers across the inner membrane 10 H+ / 1 NADH+H+ (4 + 2 + 4) or 6 H+ / 1 FADH2 (2 + 4).
So the final stoichiometry is
1 NADH+H+ : 10 H+ : 10/4 ATP = 1 NADH+H+ : 2.5 ATP
1 FADH2 : 6 H+ : 6/4 ATP = 1 FADH2 : 1.5 ATP
ATP : NADH+H+ coming from glycolysis ratio during the oxidative phosphorylation is
1.5, as for FADH2, if hydrogen atoms (2H++2e−) are transferred from cytosolic NADH+H+ to mitochondrial FAD by theglycerol phosphate shuttle located in the inner mitochondrial membrane.
2.5 in case ofmalate-aspartate shuttle transferring hydrogen atoms from cytosolic NADH+H+ to mitochondrial NAD+
Altogether this gives 4 + 3 (or 5) + 20 + 3 = 30 (or 32) ATP per molecule of glucose
These figures may still require further tweaking as new structural details become available. The above value of 3 H+ / ATP for the synthase assumes that the synthase translocates 9 protons, and produces 3 ATP, per rotation. The number of protons depends on the number of c subunits in theFo c-ring, and it is now known that this is 10 in yeast Fo[17] and 8 for vertebrates.[18] Including one H+ for the transport reactions, this means that synthesis of one ATP requires1 + 10/3 = 4.33 protons inyeast and1 + 8/3 = 3.67 invertebrates. This would imply that in human mitochondria the 10 protons from oxidizing NADH would produce 2.72 ATP (instead of 2.5) and the 6 protons from oxidizing succinate or ubiquinol would produce 1.64 ATP (instead of 1.5). This is consistent with experimental results within the margin of error described in a recent review.[19]
Without oxygen, pyruvate (pyruvic acid) is notmetabolized by cellular respiration but undergoes a process offermentation. The pyruvate is not transported into the mitochondrion but remains in the cytoplasm, where it is converted towaste products that may be removed from the cell. This serves the purpose of oxidizing the electron carriers so that they can perform glycolysis again and removing the excess pyruvate. Fermentation oxidizes NADH to NAD+ so it can be re-used in glycolysis. In the absence of oxygen, fermentation prevents the buildup of NADH in the cytoplasm and provides NAD+ for glycolysis. This waste product varies depending on the organism. In skeletal muscles, the waste product islactic acid. This type of fermentation is calledlactic acid fermentation. In strenuous exercise, when energy demands exceed energy supply, the respiratory chain cannot process all of the hydrogen atoms joined by NADH. During anaerobic glycolysis, NAD+ regenerates when pairs of hydrogen combine with pyruvate to form lactate. Lactate formation is catalyzed by lactate dehydrogenase in a reversible reaction. Lactate can also be used as an indirect precursor for liver glycogen. During recovery, when oxygen becomes available, NAD+ attaches to hydrogen from lactate to form ATP. In yeast, the waste products areethanol andcarbon dioxide. This type of fermentation is known as alcoholic orethanol fermentation. The ATP generated in this process is made bysubstrate-level phosphorylation, which does not require oxygen.
Fermentation is less efficient at using the energy from glucose: only 2 ATP are produced per glucose, compared to the 38 ATP per glucose nominally produced by aerobic respiration. Glycolytic ATP, however, is produced more quickly. Forprokaryotes to continue a rapid growth rate when they are shifted from an aerobic environment to an anaerobic environment, they must increase the rate of the glycolytic reactions. For multicellular organisms, during short bursts of strenuous activity, muscle cells use fermentation to supplement the ATP production from the slower aerobic respiration, so fermentation may be used by a cell even before the oxygen levels are depleted, as is the case in sports that do not require athletes to pace themselves, such assprinting.
Cellular respiration is the process by which biological fuels are oxidised in the presence of an inorganic electron acceptor, such as oxygen, to produce large amounts of energy and drive the bulk production of ATP.
Anaerobic respiration is used by microorganisms, eitherbacteria orarchaea, in which neither oxygen (aerobic respiration) nor pyruvate derivatives (fermentation) is the final electron acceptor. Rather, an inorganic acceptor such assulfate (SO2−4),nitrate (NO−3), orsulfur (S) is used.[20] Such organisms could be found in unusual places such as underwater caves or nearhydrothermal vents at the bottom of the ocean.,[7]: 66–68 as well as in anoxic soils or sediment in wetland ecosystems.
In July 2019, a scientific study ofKidd Mine in Canada discoveredsulfur-breathing organisms which live 7900 feet (2400 meters) below the surface. These organisms are also remarkable because they consume minerals such aspyrite as their food source.[21][22][23]
^Reece, Jane; Urry, Lisa; Cain, Michael; Wasserman, Steven; Minorsky, Peter; Jackson, Robert (2010).Campbell Biology Ninth Edition. Pearson Education, Inc. p. 168.
^Chaudhry, Raheel; Varacallo, Matthew A. (2025),"Biochemistry, Glycolysis",StatPearls, Treasure Island (FL): StatPearls Publishing,PMID29493928, retrieved2025-01-31
^abcStryer, Lubert (1995).Biochemistry (fourth ed.). New York – Basingstoke: W. H. Freeman and Company.ISBN978-0716720096.
^Stock, Daniela; Leslie, Andrew G. W.; Walker, John E. (1999). "Molecular architecture of the rotary motor in ATP synthase".Science.286 (5445):1700–5.doi:10.1126/science.286.5445.1700.PMID10576729.
^P.Hinkle (2005). "P/O ratios of mitochondrial oxidative phosphorylation".Biochimica et Biophysica Acta (BBA) - Bioenergetics.1706 (1–2):1–11.doi:10.1016/j.bbabio.2004.09.004.PMID15620362.
^Lumen Boundless Microbiology."Anaerobic Respiration-Electron Donors and Acceptors in Anaerobic Respiration".courses.lumenlearning.org. Boundless.com. RetrievedNovember 19, 2020.Anaerobic respiration is the formation of ATP without oxygen. This method still incorporates the respiratory electron transport chain, but without using oxygen as the terminal electron acceptor. Instead, molecules such as sulfate (SO2−4), nitrate (NO−3), or sulfur (S) are used as electron acceptors
^Lollar, Garnet S.; Warr, Oliver; Telling, Jon; Osburn, Magdalena R.; Sherwood Lollar, Barbara (2019). "'Follow the Water': Hydrogeochemical Constraints on Microbial Investigations 2.4 km Below Surface at the Kidd Creek Deep Fluid and Deep Life Observatory".Geomicrobiology Journal.36 (10):859–872.Bibcode:2019GmbJ...36..859L.doi:10.1080/01490451.2019.1641770.S2CID199636268.
