Editing Cellular respiration (section)

== 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 |last=Chaudhry |first=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 |last=Haddad |first=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 |last=Deshpande |first=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>