Editing Cellular respiration

{{Short description|Process to convert glucose to ATP in cells}}
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[[Image:CellRespiration.svg|thumb|upright=2.5|Typical [[eukaryote|eukaryotic cell]]]]
'''Cellular respiration''' is the process of [[Oxidation state|oxidizing]] biological fuels using an [[Electron acceptor|inorganic electron acceptor]], such as [[oxygen]], to drive production of [[Adenosine triphosphate|adenosine triphosphate (ATP)]], which stores chemical energy in a biologically accessible form. Cellular respiration may be described as a set of [[metabolism|metabolic]] reactions and processes that take place in the [[cell (biology)|cell]]s of [[organism]]s to transfer [[Energy#Energy and life|chemical energy]] from [[nutrient]]s to ATP, with the flow of electrons to an electron acceptor, and then release [[waste products]].<ref>{{cite web|last=Bailey|first=Regina|title=Cellular Respiration|url=http://biology.about.com/od/cellularprocesses/a/cellrespiration.htm|url-status=live|archive-url=https://web.archive.org/web/20120505043947/http://biology.about.com/od/cellularprocesses/a/cellrespiration.htm|archive-date=2012-05-05}}</ref>

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.<ref>{{Cite web |title=Metabolism Without Oxygen - OpenStax Biology 2E|url=https://openstax.org/books/biology-2e/pages/7-5-metabolism-without-oxygen |access-date=2025-03-21 |website=openstax.org|date=28 March 2018 }}</ref>

The reactions involved in respiration are [[catabolism|catabolic 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 are [[redox]] reactions. Although cellular respiration is technically a [[combustion 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 include [[sugar]], [[amino acids]] and [[fatty acids]], and the most common [[oxidizing agent]] is molecular [[oxygen]] (O<sub>2</sub>). 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, including [[biosynthesis]], [[motion (physics)#Cells|locomotion]] or transportation of molecules across [[cell membrane]]s.

== Aerobic respiration ==
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'''Aerobic respiration''' requires [[oxygen]] (O<sub>2</sub>) in order to create [[Adenosine triphosphate|ATP]]. Although [[carbohydrates]], [[fat]]s and [[proteins]] are consumed as [[reactants]], aerobic respiration is the preferred method of [[pyruvate]] production in [[glycolysis]], and requires pyruvate be transported by the [[mitochondria]] in order to be [[oxidized]] by the [[citric acid cycle]]. The products of this process are carbon dioxide and water, and the energy transferred is used to make bonds between ADP and a third phosphate group to form ATP ([[adenosine triphosphate]]), by [[substrate-level phosphorylation]], [[NADH dehydrogenase (ubiquinone)|NADH]] and [[FADH2|FADH<sub>2</sub>]].{{Citation needed|date=December 2023}}
{|
| rowspan = 1 | '''Mass balance of the global reaction:'''
| C<sub>6</sub>H<sub>12</sub>O<sub>6</sub> (s) + 6 O<sub>2</sub> (g) → 6 CO<sub>2</sub> (g) + 6 H<sub>2</sub>O (l) + energy
|-
| ||ΔG = −2880 kJ per mol of C<sub>6</sub>H<sub>12</sub>O<sub>6</sub>
|}

The negative ΔG indicates that the reaction is [[Exothermic process|exothermic]] ([[Exergonic reaction|exergonic]]) and can occur spontaneously.<ref>{{cite web|url=https://signalduo.com/post/how-much-atp-is-produced-in-aerobic-respiration |title=How much ATP is produced in aerobic respiration }}</ref>

The potential of NADH and FADH<sub>2</sub> is converted to more ATP through an [[electron transport chain]] with oxygen and protons (hydrogen ions) as the "[[terminal electron acceptor]]s". Most of the ATP produced by aerobic cellular respiration is made by [[oxidative phosphorylation]]. The energy released is used to create a [[chemiosmotic potential]] by pumping [[proton]]s across a membrane. This potential is then used to drive [[ATP synthase]] and produce ATP from [[adenosine diphosphate|ADP]] 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 the [[Citric acid cycle|Krebs cycle]], and about 34 from the electron transport system).<ref name=Rich>{{Cite journal| first = P. R. | title = The molecular machinery of Keilin's respiratory chain | journal = Biochemical Society Transactions | volume = 31| issue = Pt 6 | pages = 1095–1105 | year = 2003| pmid = 14641005| last = Rich | doi = 10.1042/BST0311095| url = https://www.researchgate.net/publication/8988933}}</ref> However, this maximum yield is never quite reached because of losses due to [[leaky 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.<ref name=Rich/>

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 as [[methanogen]]s are able to continue with [[anaerobic 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 of [[glycolysis]] but aerobic metabolism continues with the Krebs cycle and oxidative phosphorylation. The post-glycolytic reactions take place in the mitochondria in [[eukaryote|eukaryotic cell]]s, and in the [[cytoplasm]] in [[prokaryote|prokaryotic cell]]s.<ref>{{Cite web |last=Buckley |first=Gabe |date=2017-01-12 |title=Krebs Cycle - Definition, Products and Location |url=https://biologydictionary.net/krebs-cycle/ |access-date=2025-01-31 |website=Biology Dictionary |language=en-US}}</ref>

Although plants are net [[consumer]]s of carbon dioxide and producers of oxygen via [[photosynthesis]], plant respiration accounts for about half of the CO<sub>2</sub> generated annually by [[terrestrial ecosystem]]s.<ref>{{cite book |doi=10.1002/9780470015902.a0001301.pub3 |chapter=Plant Respiration |title=eLS |year=2016 |last1=O'Leary |first1=Brendan M. |last2=Plaxton |first2=William C. |pages=1–11 |isbn=9780470016176 }}</ref><ref name=Mannion>{{cite book |isbn=978-1-4020-3956-0 |title=Carbon and Its Domestication |last1=Mannion |first1=A. M. |date=12 January 2006 |publisher=Springer }}</ref>{{rp|87}}

===Glycolysis===
[[File:Respiration diagram.png|thumb|Out of the cytoplasm it goes into the Krebs cycle with the acetyl CoA. It then mixes with CO<sub>2</sub> 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<sup>+</sup> 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.]]
{{Main|Glycolysis}}
[[Glycolysis]] is a [[metabolic pathway]] that takes place in the [[cytosol]] of cells in all living organisms. Glycolysis can be literally translated as "sugar splitting",<ref>{{Cite book|title=Campbell Biology Ninth Edition|last1=Reece |last2=Urry |last3=Cain |last4=Wasserman |last5=Minorsky |last6=Jackson |first1=Jane |first2=Lisa |first3=Michael |first4=Steven|first5=Peter |first6=Robert|publisher=Pearson Education, Inc.|year=2010|pages=168}}</ref> and occurs regardless of oxygen's presence or absence. The process converts one molecule of [[glucose]] into two molecules of [[pyruvate]] (pyruvic acid), generating energy in the form of two net molecules of [[Adenosine triphosphate|ATP]]. Four molecules of ATP per glucose are actually produced, but two are consumed as part of the [[Glycolysis#Preparatory phase|preparatory phase]]. The initial [[phosphorylation]] of glucose is required to increase the reactivity (decrease its stability) in order for the molecule to be cleaved into two [[pyruvate]] molecules by the enzyme [[aldolase]]. During the [[Glycolysis#Pay-off phase|pay-off phase]] of glycolysis, four [[phosphate]] groups are transferred to four ADP by [[substrate-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:<ref>{{Citation |last1=Chaudhry |first1=Raheel |title=Biochemistry, Glycolysis |date=2025 |work=StatPearls |url=https://www.ncbi.nlm.nih.gov/books/NBK482303/ |access-date=2025-01-31 |place=Treasure Island (FL) |publisher=StatPearls Publishing |pmid=29493928 |last2=Varacallo |first2=Matthew A.}}</ref>

:Glucose + 2 NAD<sup>+</sup> + 2 P<sub>i</sub> + 2 ADP → 2 [[pyruvate]] + 2 NADH + 2 ATP + 2 H<sup>+</sup> + 2 H<sub>2</sub>O + energy

Starting with glucose, 1 ATP is used to donate a phosphate to glucose to produce [[glucose 6-phosphate]]. Glycogen can be converted into glucose 6-phosphate as well with the help of [[glycogen phosphorylase]]. During energy metabolism, glucose 6-phosphate becomes [[fructose 6-phosphate]]. An additional ATP is used to phosphorylate fructose 6-phosphate into [[fructose 1,6-bisphosphate]] by the help of [[phosphofructokinase]]. Fructose 1,6-biphosphate then splits into two phosphorylated molecules with three carbon chains which later degrades into pyruvate.<ref name=Mannion/>{{rp|88–90}}

===Oxidative decarboxylation of pyruvate===
{{Main|Pyruvate decarboxylation}}
Pyruvate is oxidized to [[acetyl-CoA]] and CO<sub>2</sub> by the [[pyruvate dehydrogenase complex]] (PDC). The PDC contains multiple copies of three enzymes and is located in the [[mitochondrial matrix|mitochondria]] of eukaryotic cells and in the [[cytosol]] of prokaryotes. In the conversion of pyruvate to acetyl-CoA, one molecule of NADH and one molecule of CO<sub>2</sub> is formed.<ref>{{Cite web |last=Sapkota |first=Anupama |date=2024-10-17 |title=Krebs Cycle: Steps, Enzymes, Products & Diagram |url=https://microbenotes.com/krebs-cycle/ |access-date=2025-02-01 |website=microbenotes.com |language=en-US}}</ref>

===Citric acid cycle===
{{Main|Citric acid cycle}}
The [[citric acid cycle]] is also called the ''Krebs cycle'' or the ''tricarboxylic acid cycle''. When oxygen is present, [[acetyl-CoA]] is produced from the pyruvate molecules created from glycolysis. Once [[acetyl-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 to [[Carbon dioxide|CO<sub>2</sub>]] while at the same time reducing [[Nicotinamide adenine dinucleotide|NAD]] to [[NADH]]. NADH can be used by the [[electron transport chain]] to create further [[Adenosine triphosphate|ATP]] 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-energy [[cellular waste product|waste products]], H<sub>2</sub>O and CO<sub>2</sub>, are created during this cycle.<ref name="Caspi three">{{cite web |url=https://biocyc.org/META/NEW-IMAGE?type=PATHWAY&object=PWY66-398 |title=Pathway: TCA cycle III (animals) |author=R. Caspi |publisher=MetaCyc Metabolic Pathway Database |date=2012-11-14 |access-date=2022-06-20 }}</ref><ref name="Caspi one">{{cite web |url=https://biocyc.org/META/NEW-IMAGE?type=PATHWAY&object=TCA |title=Pathway: TCA cycle I (prokaryotic) |author=R. Caspi |publisher=MetaCyc Metabolic Pathway Database |date=2011-12-19 |access-date=2022-06-20 }}</ref>

The citric acid cycle is an 8-step process involving 18 different enzymes and co-enzymes. During the cycle, acetyl-CoA (2 carbons) + [[Oxaloacetic acid|oxaloacetate]] (4 carbons) yields [[citrate]] (6 carbons), which is rearranged to a more reactive form called [[isocitrate]] (6 carbons). Isocitrate is modified to become [[Α-Ketoglutaric acid|α-ketoglutarate]] (5 carbons), [[succinyl-CoA]], [[Succinic acid|succinate]], [[fumarate]], [[malate]] and, finally, [[oxaloacetate]].<ref>{{Citation |last1=Haddad |first1=Aida |title=Biochemistry, Citric Acid Cycle |date=2025 |work=StatPearls |url=https://www.ncbi.nlm.nih.gov/books/NBK541072/ |access-date=2025-02-01 |place=Treasure Island (FL) |publisher=StatPearls Publishing |pmid=31082116 |last2=Mohiuddin |first2=Shamim S.}}</ref>

The net gain from one cycle is 3 NADH and 1 FADH<sub>2</sub> as hydrogen (proton plus electron) carrying compounds and 1 high-energy [[Guanosine triphosphate|GTP]], which may subsequently be used to produce ATP. Thus, the total yield from 1 glucose molecule (2 pyruvate molecules) is 6 NADH, 2 FADH<sub>2</sub>, and 2 ATP.<ref name="Caspi three"/><ref name="Caspi one"/><ref name=Mannion/>{{rp|90–91}}

===Oxidative phosphorylation===
{{Main|Oxidative phosphorylation|Electron transport chain|Electrochemical gradient|ATP synthase}}
[[File:Oxidative phosphorylation.svg|thumb|Diagram of oxidative phosphorylation]]
In eukaryotes, oxidative phosphorylation occurs in the mitochondrial [[crista]]e. It comprises the electron transport chain that establishes a [[proton 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 to [[exogenous]] oxygen and, with the addition of two protons, water is formed.<ref>{{Citation |last1=Deshpande |first1=Ojas A. |title=Biochemistry, Oxidative Phosphorylation |date=2025 |work=StatPearls |url=https://www.ncbi.nlm.nih.gov/books/NBK553192/ |access-date=2025-02-01 |place=Treasure Island (FL) |publisher=StatPearls Publishing |pmid=31985985 |last2=Mohiuddin |first2=Shamim S.}}</ref>

==Efficiency of ATP production==
The table below describes the reactions involved when one glucose molecule is fully oxidized into carbon dioxide. It is assumed that all the [[reduction (chemistry)|reduced]] [[coenzyme]]s are oxidized by the electron transport chain and used for oxidative phosphorylation.
{| class="wikitable"
|-
!Step
!coenzyme yield
!ATP yield
!Source of ATP
|-
| style="border-top:solid 3px #aaa;"|Glycolysis preparatory phase
| style="border-top:solid 3px #aaa;"|
| style="border-top:solid 3px #aaa; text-align:center;"| −2
| style="border-top:solid 3px #aaa;"|Phosphorylation of glucose and fructose 6-phosphate uses two ATP from the cytoplasm.
|-
|rowspan="2"|Glycolysis pay-off phase
|
| style="text-align:center;"|4
|Substrate-level phosphorylation
|-
| style="text-align:center;"|2 NADH
| style="text-align:center;"|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
| style="text-align:center;"| 2 NADH
| style="text-align:center;"| 5
|Oxidative phosphorylation
|-
|rowspan="3"|Krebs cycle
|
| style="text-align:center;"|2
|Substrate-level phosphorylation
|-
| style="text-align:center;"|6 NADH
| style="text-align:center;"|15
| Oxidative phosphorylation
|-
| style="text-align:center;"|2 FADH<sub>2</sub>
| style="text-align:center;"|3
| Oxidative phosphorylation
|-
| colspan="2" style="border-top:solid 3px #aaa; text-align:center;"|'''Total yield'''
| style="border-top:solid 3px #aaa; text-align:center;"|'''30 or 32 ATP'''
| style="border-top:solid 3px #aaa;"|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 proton [[electrochemical gradient]].{{cn|date=May 2025}}
* Pyruvate is taken up by a specific, low ''K''<sub>m</sub> transporter to bring it into the mitochondrial matrix for oxidation by the pyruvate dehydrogenase complex.
* The '''[[SLC25A3|phosphate carrier]]''' (PiC) mediates the electroneutral exchange ([[Antiporter|antiport]]) of phosphate ({{chem2|H2PO4-}}; P<sub>i</sub>) for OH<sup>−</sup> or [[Symporter|symport]] of phosphate and protons (H<sup>+</sup>) across the inner membrane, and the driving force for moving phosphate ions into the mitochondria is the [[Chemiosmosis#Proton-motive force|proton motive force]].
* The '''[[ATP-ADP translocase]]''' (also called [[Adenine nucleotide translocator|adenine nucleotide translocase, ANT]]) is an [[antiporter]] and exchanges ADP and ATP across the [[Inner nuclear membrane|inner 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<sup>+</sup> 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.<ref name=Rich/> In practice the efficiency may be even lower because the inner membrane of the mitochondria is slightly leaky to protons.<ref>{{Cite journal
| pmid = 7654171
| date = 1 September 1995
| title = Mitochondrial proton conductance and H<sup>+</sup>/O ratio are independent of electron transport rate in isolated hepatocytes
| volume = 310 | first2 = M.
| issue =  Pt 2
| last2 = Brand
| last1 = Porter
| pages = 379–382
| issn = 0264-6021
| pmc = 1135905 | first1 = R.
| journal = The Biochemical Journal
| type = Free full text
 | doi=10.1042/bj3100379}}</ref> Other factors may also dissipate the proton gradient creating an apparently leaky mitochondria. An uncoupling protein known as [[thermogenin]] 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 the [[electron transport chain]] and [[ATP synthase|ATP synthesis]]. The potential energy from the proton gradient is not used to make ATP but generates heat. This is particularly important in [[Brown adipose tissue|brown fat]] thermogenesis of newborn and hibernating mammals.{{cn|date=May 2025}}

[[File:Cellular respiration.gif|thumb|[[Stoichiometry]] of [[aerobic respiration]] and most known [[Fermentation (biochemistry)|fermentation]] types in [[Eucaryota|eucaryotic]] cell. {{r|Stryer95}} Numbers in circles indicate counts of carbon atoms in molecules, C6 is [[glucose]] C<sub>6</sub>H<sub>12</sub>O<sub>6</sub>, C1 [[carbon dioxide]] CO<sub>2</sub>. [[Mitochondrion|Mitochondrial]] outer membrane is omitted.]]
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 {{r|Stryer95}}, because:
* ATP : NADH+H<sup>+</sup> and ATP : FADH<sub>2</sub> ratios during the [[oxidative phosphorylation]] appear to be not 3 and 2, but 2.5 and 1.5 respectively. Unlike in the [[substrate-level phosphorylation]], the [[stoichiometry]] here is difficult to establish.
** [[ATP synthase]] produces 1 ATP / 3 H<sup>+</sup>. However the exchange of matrix ATP for cytosolic ADP and Pi (antiport with OH<sup>−</sup> or symport with H<sup>+</sup>) mediated by [[ATP–ADP translocase]] and [[SLC25A3|phosphate carrier]] consumes 1 H<sup>+</sup> / 1 ATP as a result of regeneration of the transmembrane potential changed during this transfer, so the net ratio is 1 ATP : 4 H<sup>+</sup>.
** The mitochondrial [[electron transport chain]] [[proton pump]] transfers across the inner membrane 10 H<sup>+</sup> / 1 NADH+H<sup>+</sup> (4 + 2 + 4) or 6 H<sup>+</sup> / 1 FADH<sub>2</sub> (2 + 4).
:So the final stoichiometry is
:1 NADH+H<sup>+</sup> : 10 H<sup>+</sup> : 10/4 ATP = 1 NADH+H<sup>+</sup> : 2.5 ATP
:1 FADH<sub>2</sub> : 6 H<sup>+</sup> : 6/4 ATP = 1 FADH<sub>2</sub> : 1.5 ATP
* ATP : NADH+H<sup>+</sup> coming from glycolysis ratio during the oxidative phosphorylation is
** 1.5, as for FADH<sub>2</sub>, if hydrogen atoms (2H<sup>+</sup>+2e<sup>−</sup>) are transferred from cytosolic NADH+H<sup>+</sup> to mitochondrial FAD by the [[glycerol phosphate shuttle]] located in the inner mitochondrial membrane.
** 2.5 in case of [[malate-aspartate shuttle]] transferring hydrogen atoms from cytosolic NADH+H<sup>+</sup> to mitochondrial NAD<sup>+</sup>

So finally we have, per molecule of glucose
* [[Substrate-level phosphorylation]]: 2 ATP from [[glycolysis]] + 2 ATP (directly GTP) from [[Krebs cycle]]
* [[Oxidative phosphorylation]]
** 2 NADH+H<sup>+</sup> from glycolysis: 2 × 1.5 ATP (if glycerol phosphate shuttle transfers hydrogen atoms) or 2 × 2.5 ATP (malate-aspartate shuttle)
** 2 NADH+H<sup>+</sup> from the [[Pyruvate decarboxylation|oxidative decarboxylation of pyruvate]] and 6 from Krebs cycle: 8 × 2.5 ATP
** 2 FADH<sub>2</sub> from the Krebs cycle: 2 × 1.5 ATP
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<sup>+</sup> / 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 the [[ATP synthase#FO region|Fo c-ring]], and it is now known that this is 10 in yeast Fo<ref>{{cite journal |title=Molecular architecture of the rotary motor in ATP synthase |journal=Science| volume = 286| pages = 1700–5 | year = 1999|issue= 5445| pmid =10576729| doi=10.1126/science.286.5445.1700|last1=Stock |first1=Daniela |last2=Leslie |first2=Andrew G. W. |last3=Walker |first3=John E. }}</ref> and 8 for vertebrates.<ref>{{cite journal |title=Bioenergetic Cost of Making an Adenosine Triphosphate Molecule in Animal Mitochondria |journal=Proc. Natl. Acad. Sci. USA| volume = 107| pages = 16823–16827 | year = 2010|issue=39 | pmid = 20847295 | doi=10.1073/pnas.1011099107 | pmc=2947889|doi-access=free |last1=Watt |first1=Ian N. |last2=Montgomery |first2=Martin G. |last3=Runswick |first3=Michael J. |last4=Leslie |first4=Andrew G. W. |last5=Walker |first5=John E. |bibcode=2010PNAS..10716823W }}</ref> Including one H<sup>+</sup> for the transport reactions, this means that synthesis of one ATP requires {{nowrap|1 + 10/3 {{=}} 4.33}} protons in [[yeast]] and {{nowrap|1 + 8/3 {{=}} 3.67}} in [[vertebrate]]s. 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.<ref>{{cite journal |title= P/O ratios of mitochondrial oxidative phosphorylation|author =P.Hinkle|journal =Biochimica et Biophysica Acta (BBA) - Bioenergetics| volume = 1706| pages = 1–11 | year = 2005|issue =1–2| pmid = 15620362| doi=10.1016/j.bbabio.2004.09.004| doi-access = }}</ref>

The total ATP yield in ethanol or lactic acid [[Fermentation (biochemistry)|fermentation]] is only 2 molecules coming from [[glycolysis]], because pyruvate is not transferred to the [[mitochondrion]] and finally oxidized to the carbon dioxide (CO<sub>2</sub>), but reduced to [[Ethanol fermentation|ethanol]] or [[Lactic acid fermentation|lactic acid]] in the [[cytoplasm]].<ref name="Stryer95">{{cite book |last=Stryer |first=Lubert |year=1995 |title=Biochemistry |publisher=W. H. Freeman and Company |location=New York – Basingstoke |edition=fourth |isbn=978-0716720096 }}</ref>

==Fermentation==
{{Main|Fermentation}}
Without oxygen, pyruvate ([[pyruvic acid]]) is not [[Metabolism|metabolized]] by cellular respiration but undergoes a process of [[fermentation]]. The pyruvate is not transported into the mitochondrion but remains in the cytoplasm, where it is converted to [[cellular waste product|waste 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<sup>+</sup> 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<sup>+</sup> for glycolysis.  This waste product varies depending on the organism. In skeletal muscles, the waste product is [[lactic acid]]. This type of fermentation is called [[lactic 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<sup>+</sup> 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<sup>+</sup> attaches to hydrogen from lactate to form ATP. In yeast, the waste products are [[ethanol]] and [[carbon dioxide]]. This type of fermentation is known as alcoholic or [[ethanol fermentation]]. The ATP generated in this process is made by [[substrate-level phosphorylation]], which does not require oxygen.{{cn|date=May 2025}}

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. For [[prokaryote]]s 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 as [[Sprint (running)|sprinting]].{{cn|date=May 2025}}

==Anaerobic respiration==
{{Main|Anaerobic respiration}}
[[File:Anaerobic Respiration.jpg|thumb|Anaerobic Respiration is a proccess where glucose goes through glycolsis and fermentation to either produce Ethanol in yeast and some bacteria or Lactate in us humans to overall keep producing ATP.]]
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.{{cn|date=May 2025}}

'''Anaerobic respiration''' is used by microorganisms, either [[bacteria]] or [[archaea]], in which neither oxygen (aerobic respiration) nor pyruvate derivatives (fermentation) is the final electron acceptor.  Rather, an inorganic acceptor such as [[sulfate]] ({{chem2|SO4(2-)}}), [[nitrate]] ({{chem2|NO3-}}), or [[sulfur]] (S) is used.<ref>{{cite web|url= https://courses.lumenlearning.com/boundless-microbiology/chapter/anaerobic-respiration/|title=Anaerobic Respiration-Electron Donors and Acceptors in Anaerobic Respiration |author=Lumen Boundless Microbiology|website=courses.lumenlearning.org |publisher=Boundless.com |access-date=November 19, 2020 |quote="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 ({{chem2|SO4(2-)}}), nitrate ({{chem2|NO3-}}), or sulfur (S) are used as electron acceptors"}}</ref> Such organisms could be found in unusual places such as underwater caves or near [[hydrothermal vents]] at the bottom of the ocean.,<ref name=Mannion/>{{rp|66–68}} as well as in anoxic soils or sediment in wetland ecosystems.

In July 2019, a scientific study of [[Kidd Mine]] in Canada discovered [[sulfur-breathing organisms]] which live {{convert|7900|ft|m|comma=5|abbr=off|sp=us}} below the surface. These organisms are also remarkable because they consume minerals such as [[pyrite]] as their food source.<ref>{{cite journal|doi=10.1080/01490451.2019.1641770 | volume=36 | title='Follow the Water': Hydrogeochemical Constraints on Microbial Investigations 2.4 km Below Surface at the Kidd Creek Deep Fluid and Deep Life Observatory | year=2019 | journal=Geomicrobiology Journal | pages=859–872 | last1 = Lollar | first1 = Garnet S. | last2 = Warr | first2 = Oliver | last3 = Telling | first3 = Jon | last4 = Osburn | first4 = Magdalena R. | last5 = Sherwood Lollar | first5 = Barbara| issue=10 | bibcode=2019GmbJ...36..859L | s2cid=199636268 }}</ref><ref>[https://deepcarbon.net/worlds-oldest-groundwater-supports-life-through-water-rock-chemistry World's Oldest Groundwater Supports Life Through Water-Rock Chemistry] {{Webarchive|url=https://web.archive.org/web/20190910013319/https://deepcarbon.net/worlds-oldest-groundwater-supports-life-through-water-rock-chemistry |date=2019-09-10 }}, July 29, 2019, deepcarbon.net.</ref><ref>[https://www.nbcnews.com/mach/science/strange-life-forms-found-deep-mine-point-vast-underground-galapagos-ncna1050906 Strange life-forms found deep in a mine point to vast 'underground Galapagos'] {{Webarchive|url=https://web.archive.org/web/20190909104558/https://www.nbcnews.com/mach/science/strange-life-forms-found-deep-mine-point-vast-underground-galapagos-ncna1050906 |date=2019-09-09 }}, By Corey S. Powell, Sept. 7, 2019, nbcnews.com.</ref>

==See also==
* [[Maintenance respiration]]: maintenance as a functional component of cellular respiration
* [[Microphysiometry]]
* [[Pasteur point]]
* [[Respirometry]]: research tool to explore cellular respiration
* [[Tetrazolium chloride]]: cellular respiration indicator
* [[NADH dehydrogenase (ubiquinone)|Complex 1]]: NADH:ubiquinone oxidoreductes

==References==
{{Reflist}}

==External links==
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* [https://web.archive.org/web/20080917123419/http://www2.ufp.pt/~pedros/bq/respi.htm A detailed description of respiration vs. fermentation]
* [https://web.archive.org/web/20110806221826/http://users.rcn.com/jkimball.ma.ultranet/BiologyPages/C/CellularRespiration.html Kimball's online resource for cellular respiration]
* [https://web.archive.org/web/20070123180940/http://biology.clc.uc.edu/Courses/bio104/cellresp.htm Cellular Respiration and Fermentation] at Clermont College

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[[Category:Cellular respiration| ]]
[[Category:Metabolism]]
[[Category:Plant physiology]]