{"id":194,"date":"2019-04-11T04:53:34","date_gmt":"2019-04-11T04:53:34","guid":{"rendered":"http:\/\/biocp04.epgpbooks.inflibnet.ac.in\/?post_type=chapter&#038;p=194"},"modified":"2019-04-11T04:59:03","modified_gmt":"2019-04-11T04:59:03","slug":"stoichiometry-of-citric-acid-cycle","status":"publish","type":"chapter","link":"https:\/\/ebooks.inflibnet.ac.in\/biocp04\/chapter\/stoichiometry-of-citric-acid-cycle\/","title":{"rendered":"Stoichiometry of Citric Acid Cycle"},"content":{"raw":"<div><span style=\"float: right\"><a href=\"https:\/\/youtu.be\/26LjokJoAYA\" target=\"_blank\" rel=\"noopener\"><img src=\"http:\/\/epgpbooks.inflibnet.ac.in\/wp-content\/uploads\/2018\/11\/download.png\" alt=\"epgp books\" width=\"75px\" height=\"75px;\" \/><\/a>\r\n<\/span><\/div>\r\n<strong>\u00a0<\/strong>\r\n\r\n&nbsp;\r\n\r\n&nbsp;\r\n\r\n&nbsp;\r\n\r\n<strong>Stoichiometry of Citric Acid Cycle<\/strong>\r\n\r\n&nbsp;\r\n\r\n<strong>Objectives<\/strong>\r\n<ol>\r\n \t<li style=\"text-align: justify\">To understand the function of citric acid cycle in production of NADPH and FADH for synthesis of energy.<\/li>\r\n \t<li style=\"text-align: justify\">To examine energy yield for the complete oxidation of pyruvate.<\/li>\r\n<\/ol>\r\n<strong>\u00a0 \u00a0 Introduction<\/strong>\r\n<ul>\r\n \t<li style=\"text-align: justify\">The reactions of the tricarboxylic acid (TCA) cycle (also known as citric acid cycle) can be divided into two phases.<\/li>\r\n<\/ul>\r\n<p style=\"text-align: justify\">\u00a0 \u00a0 \u00a01) Citrate with \u2018two carbon atoms\u2019are oxidized to CO2, with the formation of \u2018four carbon compound\u2019 Succinyl-CoA, (Figure 1).<\/p>\r\n&nbsp;\r\n\r\n&nbsp;\r\n<p style=\"text-align: justify\">\u00a0 \u00a02) Later is further converted intooxaloacetate thus making it possible to begin the process again. In each cycle of the TCA, two carbons comes from acetyl-CoA and two carbons are oxidized into CO2. Thus, during each turn of the cycle there is no involvement of carbons from acetyl-CoA.<\/p>\r\n\r\n<ul>\r\n \t<li style=\"text-align: justify\">Acetyl-CoA is an \"activated\" two carbon compound, is a key molecule in numerous central metabolic pathways, like the Glyoxylate cycle, the TCA, fatty acid synthesis, fatty acid oxidation, amino sugar metabolism, isoprene metabolism, ketone body metabolism, and cholesterol biosynthesis.<\/li>\r\n<\/ul>\r\n<ul>\r\n \t<li style=\"text-align: justify\">The high energy thioester bond present in the molecule (DG0' of -7.53 kcal\/mol) is partially responsible for making molecule \u201cactivated\". The carbon dioxide released during TCA cycle comes from acetyl groups added in previous cycles instead Acetyl-CoA. Thus, it takes minimum two complete run of TCAcycle<span style=\"text-align: initial;font-size: 1em\"> in order to make the carbons available an acetyl-CoA to release as carbon dioxide.<\/span><\/li>\r\n<\/ul>\r\n<img class=\"aligncenter size-full wp-image-195\" src=\"http:\/\/biocp04.epgpbooks.inflibnet.ac.in\/wp-content\/uploads\/sites\/215\/2019\/04\/1-93.png\" alt=\"\" width=\"323\" height=\"363\" \/>\r\n<h2 style=\"text-align: center\"><strong>Figure \u2013 1 Stoichiometry of the TCA Cycle<\/strong><\/h2>\r\n<strong>\u00a0 \u00a0 \u00a0\u00a0Stoichiometry of the Cycle<\/strong>\r\n<ul>\r\n \t<li style=\"text-align: justify\">First two carbon atoms enter in the cycle by a condensation reaction which involvesan acetyl unit (from acetyl CoA) and oxaloacetate.<\/li>\r\n<\/ul>\r\n<ul>\r\n \t<li style=\"text-align: justify\">The isocitrate dehydrogenase and \u03b1-ketoglutarate dehydrogenase catalyses decarboxylation reaction involving removal of two carbon atomsasCO2. Theisotope-labelling studies implicated that the two carbon atoms that exit from cycle are distinct from which enter each cycle.<\/li>\r\n<\/ul>\r\n<ul>\r\n \t<li style=\"text-align: justify\">Through four oxidation reactions, four sets of hydrogen atoms leave the cycle. Two molecules of NAD+ reduced during oxidative decarboxylation of isocitrate and \u03b1-ketoglutarate. A molecule of FAD and NAD+ reduced by oxidation of succinateand malaterespectively.<\/li>\r\n<\/ul>\r\n<ul>\r\n \t<li style=\"text-align: justify\">The cleavage of the thioester linkage ofSuccinyl CoA generates high phosphoryl transfer potential GTP.<\/li>\r\n<\/ul>\r\n<ul>\r\n \t<li>In the TCA cycle we used two molecule of water<\/li>\r\n<\/ul>\r\n<p style=\"text-align: justify\">\u00a0 \u00a0 (i) It is used in formation of citrate from citryl CoAin a hydrolysis step<\/p>\r\n<p style=\"text-align: justify\">(ii) Fumarate hydration.<\/p>\r\n\r\n<ul>\r\n \t<li style=\"text-align: justify\">Acetyl CoA is formed from pyruvate with formation of NADH and reaction is catalysed by pyruvate dehydrogenase complex.<\/li>\r\n<\/ul>\r\n<ul>\r\n \t<li style=\"text-align: justify\">In short we get 2.5 ATP per NADH, and 1.5 ATP per FADH2 molecule. Nine high potential phosphoryl groups are produced by the oxidation of three molecules of NADH and a molecule of FADH2 and a high potential phosphoryl group is directly generatedfrom<span style=\"text-align: initial;font-size: 1em\"> each acetyl unit<\/span>.Hence<span style=\"text-align: initial;font-size: 1em\"> net output is 10 ATP molecules from each Acetyl CoA molecule.<\/span><\/li>\r\n<\/ul>\r\n&nbsp;\r\n\r\nFollowing reactions explains stoichiometric reactions involved in TCA cycles.\r\n<ul>\r\n \t<li>Stoichiometry for Pyruvate conversion to Acetyl-CoA:<\/li>\r\n<\/ul>\r\n<img class=\"aligncenter size-full wp-image-196\" src=\"http:\/\/biocp04.epgpbooks.inflibnet.ac.in\/wp-content\/uploads\/sites\/215\/2019\/04\/1-94.png\" alt=\"\" width=\"401\" height=\"34\" \/>\r\n<ul>\r\n \t<li>The stoichiometry of TCA cycle from Acetyl CoA:<\/li>\r\n<\/ul>\r\n<img class=\"aligncenter size-full wp-image-197\" src=\"http:\/\/biocp04.epgpbooks.inflibnet.ac.in\/wp-content\/uploads\/sites\/215\/2019\/04\/1-95.png\" alt=\"\" width=\"592\" height=\"39\" \/>\r\n<ul>\r\n \t<li>The stoichiometry of TCA cycle via Glycolysis:<\/li>\r\n<\/ul>\r\n<img class=\"aligncenter size-full wp-image-198\" src=\"http:\/\/biocp04.epgpbooks.inflibnet.ac.in\/wp-content\/uploads\/sites\/215\/2019\/04\/1-96.png\" alt=\"\" width=\"569\" height=\"40\" \/>\r\n<ul>\r\n \t<li>The net reaction of the TCA is:<\/li>\r\n<\/ul>\r\n<img class=\"aligncenter size-full wp-image-199\" src=\"http:\/\/biocp04.epgpbooks.inflibnet.ac.in\/wp-content\/uploads\/sites\/215\/2019\/04\/1-97.png\" alt=\"\" width=\"624\" height=\"33\" \/>\r\n\r\n&nbsp;\r\n<p style=\"text-align: justify\">ATP is formed from NADH and FADH2 molecules via electron transfer chain and we get 3 ATP molecules per NADH and 2 ATP molecules per FADH2. This way we get 38 ATPs from one molecule of glucose.<\/p>\r\n&nbsp;\r\n<ul>\r\n \t<li style=\"text-align: justify\">Energy calculation in kJ\/mol as 38 x 30.5 kJ\/mol = 1,160 kJ\/mol, or 40% of the theoretical maximum of 2,840 kJ\/mol available via complete oxidation of glucose.<\/li>\r\n<\/ul>\r\n<strong>Table 1. The stoichiometry of coenzyme reduction and ATP formation in the aerobic oxidation of a molecule of pyruvate by TCA cycle.<\/strong>\r\n\r\n&nbsp;\r\n\r\n<img class=\"aligncenter size-full wp-image-200\" src=\"http:\/\/biocp04.epgpbooks.inflibnet.ac.in\/wp-content\/uploads\/sites\/215\/2019\/04\/1-98.png\" alt=\"\" width=\"603\" height=\"396\" \/>\r\n\r\n<strong>\u00a0 \u00a0 \u00a0 \u00a0 \u00a0 \u00a0 \u00a0 \u00a0 \u00a0 \u00a0 \u00a0 \u00a0 \u00a0 \u00a0 \u00a0 *This is calculated as 3 ATP per NADH and 2 ATP per FADH<\/strong><strong>2<\/strong><strong>.<\/strong>\r\n\r\n&nbsp;\r\n\r\n&nbsp;\r\n\r\n<strong>Reactions of Stoichiometry:<\/strong>\r\n\r\nEnergetic involved\r\n\r\n&nbsp;\r\n\r\n3 NADH+3H+ are formed during one turn of each cycle\r\n\r\n&nbsp;\r\n<p style=\"text-align: justify\">Around 3 ATP formed per NADH+H+ by electron transport and oxidative phosphorylation 1 FADH2 formed during one turn of TCA cycle<\/p>\r\n&nbsp;\r\n\r\n2 ATP formed per FADH2 by electron transport and oxidative phosphorylation\r\n\r\n&nbsp;\r\n<p style=\"text-align: justify\">1 GTP are formed per turn (equivalent to 1 ATP) (during succinate thiokinase step) Total equivalent of 12 ATP formed during each turn of TCA cycle<\/p>\r\n&nbsp;\r\n\r\n2 turns required for 2 acetyl-CoA's results in an equivalent of 24 ATP\/2 acetyl-CoA\r\n\r\n&nbsp;\r\n\r\n&nbsp;\r\n\r\n&nbsp;\r\n\r\n<strong>Table 2. Stoichiometry of TCA by che mical equation, enzyme responsible for it and free energy release or gain in kJ\/mol.<\/strong>\r\n\r\n&nbsp;\r\n\r\n<img class=\"aligncenter size-full wp-image-201\" src=\"http:\/\/biocp04.epgpbooks.inflibnet.ac.in\/wp-content\/uploads\/sites\/215\/2019\/04\/1-99.png\" alt=\"\" width=\"617\" height=\"527\" \/>\r\n<ul>\r\n \t<li style=\"text-align: justify\">Moreover, organic\u00a0 substrates\u00a0 serves\u00a0 as\u00a0 source\u00a0 for\u00a0 reducing\u00a0 hydrogens\u00a0 in\u00a0 the mitochondria. Pyruvic acid is completely oxidizedwith<span style=\"text-align: initial;font-size: 1em\"> production of 10 reducing hydrogen ions (4 NADH\/H \u00f7 and 1 FADH2), is able to reduce 2.5 O2 with <\/span>formation<span style=\"text-align: initial;font-size: 1em\"> of 5 H20. In <\/span>theoretically ,<span style=\"text-align: initial;font-size: 1em\"> the equation for pyruvic acid oxidation looks nonstoichiometric with 6 H missing<\/span><\/li>\r\n<\/ul>\r\n<img class=\"aligncenter size-full wp-image-202\" src=\"http:\/\/biocp04.epgpbooks.inflibnet.ac.in\/wp-content\/uploads\/sites\/215\/2019\/04\/1-100.png\" alt=\"\" width=\"363\" height=\"26\" \/>\r\n<ul>\r\n \t<li style=\"text-align: justify\">Pyruvic acid containing only 4 H with,task will be to identify the entries for the missing hydrogen and also 3 oxygen in the form of X. However, entry<span style=\"text-align: initial;font-size: 1em\"> of three water (H2O)in the cycle would satisfy the stoichiometry.<\/span><\/li>\r\n<\/ul>\r\n<ul style=\"text-align: justify\">\r\n \t<li>Moreover, at physiological pH, pyruvate exist in anionic form. During the decarboxylation reaction catalysed by pyruvate dehydrogenase complex, pyruvate gets one proton from product in the form of hydroxyethyl.<\/li>\r\n<\/ul>\r\n<ul>\r\n \t<li style=\"text-align: justify\">Hence, pyruvate contributes for \u201ceffective number\u201dof 4H like pyruvic acid. Referring only to the cycle, the correct stoichiometry of acetyl CoA oxidation will be as follows:<\/li>\r\n<\/ul>\r\n<img class=\"aligncenter size-full wp-image-203\" src=\"http:\/\/biocp04.epgpbooks.inflibnet.ac.in\/wp-content\/uploads\/sites\/215\/2019\/04\/1-101.png\" alt=\"\" width=\"453\" height=\"29\" \/>\r\n<ul>\r\n \t<li>Since the process yields 8 reducing equivalents (3 NADH\/ H + + 1 FADH2).<\/li>\r\n<\/ul>\r\n<ul>\r\n \t<li style=\"text-align: justify\">According to Lenhinger, the net reaction of stoichiometry of TCAwould involve anaccess of 7 H and anwithdrawal of 9 H:<\/li>\r\n<\/ul>\r\n<img class=\"aligncenter size-full wp-image-204\" src=\"http:\/\/biocp04.epgpbooks.inflibnet.ac.in\/wp-content\/uploads\/sites\/215\/2019\/04\/1-102.png\" alt=\"\" width=\"615\" height=\"51\" \/>\r\n<ul>\r\n \t<li style=\"text-align: justify\">H2O molecules involved in the reaction catalysed by citrate synthetase (aldol bond formation) and Fumarase (addition of H2O to form malate) serves as source for additional stoichiometric 4H hydrogens in pyruvate oxidation.<\/li>\r\n<\/ul>\r\n<ul>\r\n \t<li style=\"text-align: justify\">In fact, this H2O enters indirectly via the cleavage of Succinyl-CoA thioester equivalent to a hydrolysis reaction without the intervention of molecular H2O.<\/li>\r\n<\/ul>\r\n<ul>\r\n \t<li style=\"text-align: justify\">The cleavage of the thioester occurs through a phospholysis of a H2O equivalent from of orthophosphate. This step offersthe<span style=\"text-align: initial;font-size: 1em\"> drop of free energy needed for the ATP phosphorylation. This is equivalent to removal of H2Oinvolved in <\/span>ATPsynthesis<span style=\"text-align: initial;font-size: 1em\"> during oxidative phosphorylation.<\/span><\/li>\r\n<\/ul>\r\n<ul>\r\n \t<li>Thus, this extra H2O entering the Krebs cycle is carried by phosphate.<\/li>\r\n<\/ul>\r\n&nbsp;\r\n\r\n&nbsp;\r\n<p style=\"text-align: justify\"><strong>Table 3.Represent stoichiometry of TCA by a requirement of Prosthetic group, type of reaction and energy release or gain in kcal\/mol and kJ\/mol (Adapted from - Biochemistry 5th edition by Berg JM, Tymoczko JL<\/strong>, <strong>Stryer L)<\/strong><\/p>\r\n&nbsp;\r\n\r\n<img class=\"aligncenter size-full wp-image-205\" src=\"http:\/\/biocp04.epgpbooks.inflibnet.ac.in\/wp-content\/uploads\/sites\/215\/2019\/04\/1-103.png\" alt=\"\" width=\"554\" height=\"541\" \/>\r\n\r\n&nbsp;\r\n\r\n<strong>Regulation of stoichiometry of the TCA<\/strong>\r\n<ul>\r\n \t<li style=\"text-align: justify\">The TCA must be optimally regulated by the cell. The uncontrolled TCA could led toproduction of very big amount of metabolic energy and wastage in form of ATP.<\/li>\r\n<\/ul>\r\n<ul>\r\n \t<li style=\"text-align: justify\">If the TCA cycle go slowly then the formation of ATP also too slow which help the cell to sustain. There are three irreversible reactions catalysed<span style=\"text-align: initial;font-size: 1em\"> by citrate synthase, isocitrate dehydrogenase and \u03b1-ketoglutarate dehydrogenase function <\/span>withhigher<span style=\"text-align: initial;font-size: 1em\"> -D G\u00a0<\/span>value<span style=\"text-align: initial;font-size: 1em\"> in <\/span>mitochondrial<span style=\"text-align: initial;font-size: 1em\"> matrix at high concentrations of products and reactants. The <\/span>TCAcycle<span style=\"text-align: initial;font-size: 1em\"> is linked to oxygen consumption for the regeneration of NAD+<\/span>,TCA<span style=\"text-align: initial;font-size: 1em\"> cycle is regulated by feedback inhibition.<\/span><\/li>\r\n<\/ul>\r\n<ul>\r\n \t<li>The TCA is regulated by three simple mechanisms.<\/li>\r\n<\/ul>\r\n<p style=\"text-align: justify\">\u00a0 \u00a0 (i) Availability of substrate<\/p>\r\n<p style=\"text-align: justify\">(ii) Inhibition by end product formed<\/p>\r\n&nbsp;\r\n<ul>\r\n \t<li style=\"text-align: justify\">Competitive feedback inhibition. Molecules such as acetyl-CoA, Succinyl-CoA, ATP, ADP, AMP, NAD+ and NADH serve as the allosteric effectors<\/li>\r\n<\/ul>\r\n<ul style=\"text-align: justify\">\r\n \t<li>In the TCA cycle all regulatory enzymes also include pyruvate dehydrogenase are allosterically inhibited by NADH and ATP.<\/li>\r\n<\/ul>\r\n<ul>\r\n \t<li style=\"text-align: justify\">The TCA\u00a0 cycle operated\u00a0 based\u00a0 on signal of\u00a0 high ratios\u00a0 of either\u00a0 ADP\/ATP\u00a0 or NAD+\/NADH which based on requirement<span style=\"text-align: initial;font-size: 1em\"> of <\/span>concentration<span style=\"text-align: initial;font-size: 1em\"> of NADH or ATP in the cell.<\/span><\/li>\r\n<\/ul>\r\n&nbsp;\r\n<table>\r\n<tbody>\r\n<tr>\r\n<td><strong>you can view video on Stoichiometry of Citric Acid Cycle<\/strong><\/td>\r\n<td><a href=\"https:\/\/youtu.be\/26LjokJoAYAe\" target=\"_blank\" rel=\"noopener\"><img class=\"alignnone wp-image-120\" src=\"http:\/\/epgpbooks.inflibnet.ac.in\/wp-content\/uploads\/2018\/11\/download.png\" alt=\"\" width=\"36\" height=\"36\" \/><\/a><\/td>\r\n<\/tr>\r\n<\/tbody>\r\n<\/table>\r\n&nbsp;\r\n\r\n&nbsp;\r\n<div class=\"textbox learning-objectives\">\r\n<h3>References<\/h3>\r\n<ul>\r\n \t<li style=\"text-align: justify\">Koivunen P, Hirsil\u00e4 M, Remes AM, Hassinen IE, Kivirikko KI, Myllyharju J (February 2007). \"Inhibition of hypoxia-inducible factor (HIF) hydroxylases by citric acid cycle intermediates: possible links between cell metabolism and stabilization of HIF\". J. Biol. Chem. 282 (7): 4524\u201332. doi:10.1074\/jbc.M610415200. PMID 17182618<\/li>\r\n \t<li style=\"text-align: justify\">Madeira, V. M. C. (1988), Stoichiometry of reducing equivalents and splitting of water in the citric acid cycle. Biochemical Education, 16: 94\u201396.<\/li>\r\n \t<li style=\"text-align: justify\">H.A. Krebs and W.A. Johnson. 1937. The role of citric acid in intermediate metabolism in animal tissues <em>Enzymologia<\/em>4:148-156.<\/li>\r\n \t<li style=\"text-align: justify\">H.A. Krebs. 1970. The history of the tricarboxylic acid cycle <em>Perspect. Biol. Med.<\/em> 14: 154-170. (PubMed)<\/li>\r\n \t<li style=\"text-align: justify\">Krebs, H. A., and Martin, A., 1981. <em>Reminiscences and Reflections.<\/em> Clarendon Press.<\/li>\r\n<\/ul>\r\n&nbsp;\r\n\r\n<strong>Web site<\/strong>\r\n<ul>\r\n \t<li><a href=\"http:\/\/www.ncbi.nlm.nih.gov\/books\/NBK22427\/\">http:\/\/www.ncbi.nlm.nih.gov\/books\/NBK22427\/<\/a><\/li>\r\n \t<li><a href=\"http:\/\/oregonstate.edu\/dept\/biochem\/hhmi\/hhmiclasses\/bb451\/lectnoteskga\/citricacidcycle.html\">http:\/\/oregonstate.edu\/dept\/biochem\/hhmi\/hhmiclasses\/bb451\/lectnoteskga\/citric<\/a><a style=\"text-align: initial;text-indent: 1em;font-size: 1em\" href=\"http:\/\/oregonstate.edu\/dept\/biochem\/hhmi\/hhmiclasses\/bb451\/lectnoteskga\/citricacidcycle.html\">acidcycle.html<\/a><\/li>\r\n \t<li><a href=\"http:\/\/web.campbell.edu\/faculty\/nemecz\/323_lect\/citric_acid\/stoichiometry.html\">http:\/\/web.campbell.edu\/faculty\/nemecz\/323_lect\/citric_acid\/stoichiometry.html<\/a><\/li>\r\n \t<li><a href=\"https:\/\/www.tamu.edu\/faculty\/bmiles\/lectures\/regulationtca.pdf\">https:\/\/www.tamu.edu\/faculty\/bmiles\/lectures\/regulationtca.pdf<\/a><\/li>\r\n<\/ul>\r\n&nbsp;\r\n\r\n<strong>Books<\/strong>\r\n<ul>\r\n \t<li style=\"text-align: justify\">Harper\u2019sIllustrated Biochemistry by Robert K.. Murray, Daryl K. Granner, Peter A. Mayes, 26th Edition (2003)<\/li>\r\n \t<li style=\"text-align: justify\">Lehninger\u2019S Principle of Biochemistry David L. Nelson and Michael M. Cox,5th Edition (2008)<\/li>\r\n \t<li style=\"text-align: justify\">Biochemisty by Berg JM,TymoczkoJL,Stryer L, 5th edition. Publisher New York: W H Freeman; 2002.<\/li>\r\n<\/ul>\r\n<\/div>\r\n&nbsp;","rendered":"<div><span style=\"float: right\"><a href=\"https:\/\/youtu.be\/26LjokJoAYA\" target=\"_blank\" rel=\"noopener\"><img decoding=\"async\" src=\"http:\/\/epgpbooks.inflibnet.ac.in\/wp-content\/uploads\/2018\/11\/download.png\" alt=\"epgp books\" width=\"75px\" height=\"75px;\" \/><\/a><br \/>\n<\/span><\/div>\n<p><strong>\u00a0<\/strong><\/p>\n<p>&nbsp;<\/p>\n<p>&nbsp;<\/p>\n<p>&nbsp;<\/p>\n<p><strong>Stoichiometry of Citric Acid Cycle<\/strong><\/p>\n<p>&nbsp;<\/p>\n<p><strong>Objectives<\/strong><\/p>\n<ol>\n<li style=\"text-align: justify\">To understand the function of citric acid cycle in production of NADPH and FADH for synthesis of energy.<\/li>\n<li style=\"text-align: justify\">To examine energy yield for the complete oxidation of pyruvate.<\/li>\n<\/ol>\n<p><strong>\u00a0 \u00a0 Introduction<\/strong><\/p>\n<ul>\n<li style=\"text-align: justify\">The reactions of the tricarboxylic acid (TCA) cycle (also known as citric acid cycle) can be divided into two phases.<\/li>\n<\/ul>\n<p style=\"text-align: justify\">\u00a0 \u00a0 \u00a01) Citrate with \u2018two carbon atoms\u2019are oxidized to CO2, with the formation of \u2018four carbon compound\u2019 Succinyl-CoA, (Figure 1).<\/p>\n<p>&nbsp;<\/p>\n<p>&nbsp;<\/p>\n<p style=\"text-align: justify\">\u00a0 \u00a02) Later is further converted intooxaloacetate thus making it possible to begin the process again. In each cycle of the TCA, two carbons comes from acetyl-CoA and two carbons are oxidized into CO2. Thus, during each turn of the cycle there is no involvement of carbons from acetyl-CoA.<\/p>\n<ul>\n<li style=\"text-align: justify\">Acetyl-CoA is an &#8220;activated&#8221; two carbon compound, is a key molecule in numerous central metabolic pathways, like the Glyoxylate cycle, the TCA, fatty acid synthesis, fatty acid oxidation, amino sugar metabolism, isoprene metabolism, ketone body metabolism, and cholesterol biosynthesis.<\/li>\n<\/ul>\n<ul>\n<li style=\"text-align: justify\">The high energy thioester bond present in the molecule (DG0&#8242; of -7.53 kcal\/mol) is partially responsible for making molecule \u201cactivated&#8221;. The carbon dioxide released during TCA cycle comes from acetyl groups added in previous cycles instead Acetyl-CoA. Thus, it takes minimum two complete run of TCAcycle<span style=\"text-align: initial;font-size: 1em\"> in order to make the carbons available an acetyl-CoA to release as carbon dioxide.<\/span><\/li>\n<\/ul>\n<p><img loading=\"lazy\" decoding=\"async\" class=\"aligncenter size-full wp-image-195\" src=\"http:\/\/biocp04.epgpbooks.inflibnet.ac.in\/wp-content\/uploads\/sites\/215\/2019\/04\/1-93.png\" alt=\"\" width=\"323\" height=\"363\" srcset=\"https:\/\/ebooks.inflibnet.ac.in\/biocp04\/wp-content\/uploads\/sites\/215\/2019\/04\/1-93.png 323w, https:\/\/ebooks.inflibnet.ac.in\/biocp04\/wp-content\/uploads\/sites\/215\/2019\/04\/1-93-267x300.png 267w, https:\/\/ebooks.inflibnet.ac.in\/biocp04\/wp-content\/uploads\/sites\/215\/2019\/04\/1-93-65x73.png 65w, https:\/\/ebooks.inflibnet.ac.in\/biocp04\/wp-content\/uploads\/sites\/215\/2019\/04\/1-93-225x253.png 225w\" sizes=\"auto, (max-width: 323px) 100vw, 323px\" \/><\/p>\n<h2 style=\"text-align: center\"><strong>Figure \u2013 1 Stoichiometry of the TCA Cycle<\/strong><\/h2>\n<p><strong>\u00a0 \u00a0 \u00a0\u00a0Stoichiometry of the Cycle<\/strong><\/p>\n<ul>\n<li style=\"text-align: justify\">First two carbon atoms enter in the cycle by a condensation reaction which involvesan acetyl unit (from acetyl CoA) and oxaloacetate.<\/li>\n<\/ul>\n<ul>\n<li style=\"text-align: justify\">The isocitrate dehydrogenase and \u03b1-ketoglutarate dehydrogenase catalyses decarboxylation reaction involving removal of two carbon atomsasCO2. Theisotope-labelling studies implicated that the two carbon atoms that exit from cycle are distinct from which enter each cycle.<\/li>\n<\/ul>\n<ul>\n<li style=\"text-align: justify\">Through four oxidation reactions, four sets of hydrogen atoms leave the cycle. Two molecules of NAD+ reduced during oxidative decarboxylation of isocitrate and \u03b1-ketoglutarate. A molecule of FAD and NAD+ reduced by oxidation of succinateand malaterespectively.<\/li>\n<\/ul>\n<ul>\n<li style=\"text-align: justify\">The cleavage of the thioester linkage ofSuccinyl CoA generates high phosphoryl transfer potential GTP.<\/li>\n<\/ul>\n<ul>\n<li>In the TCA cycle we used two molecule of water<\/li>\n<\/ul>\n<p style=\"text-align: justify\">\u00a0 \u00a0 (i) It is used in formation of citrate from citryl CoAin a hydrolysis step<\/p>\n<p style=\"text-align: justify\">(ii) Fumarate hydration.<\/p>\n<ul>\n<li style=\"text-align: justify\">Acetyl CoA is formed from pyruvate with formation of NADH and reaction is catalysed by pyruvate dehydrogenase complex.<\/li>\n<\/ul>\n<ul>\n<li style=\"text-align: justify\">In short we get 2.5 ATP per NADH, and 1.5 ATP per FADH2 molecule. Nine high potential phosphoryl groups are produced by the oxidation of three molecules of NADH and a molecule of FADH2 and a high potential phosphoryl group is directly generatedfrom<span style=\"text-align: initial;font-size: 1em\"> each acetyl unit<\/span>.Hence<span style=\"text-align: initial;font-size: 1em\"> net output is 10 ATP molecules from each Acetyl CoA molecule.<\/span><\/li>\n<\/ul>\n<p>&nbsp;<\/p>\n<p>Following reactions explains stoichiometric reactions involved in TCA cycles.<\/p>\n<ul>\n<li>Stoichiometry for Pyruvate conversion to Acetyl-CoA:<\/li>\n<\/ul>\n<p><img loading=\"lazy\" decoding=\"async\" class=\"aligncenter size-full wp-image-196\" src=\"http:\/\/biocp04.epgpbooks.inflibnet.ac.in\/wp-content\/uploads\/sites\/215\/2019\/04\/1-94.png\" alt=\"\" width=\"401\" height=\"34\" srcset=\"https:\/\/ebooks.inflibnet.ac.in\/biocp04\/wp-content\/uploads\/sites\/215\/2019\/04\/1-94.png 401w, https:\/\/ebooks.inflibnet.ac.in\/biocp04\/wp-content\/uploads\/sites\/215\/2019\/04\/1-94-300x25.png 300w, https:\/\/ebooks.inflibnet.ac.in\/biocp04\/wp-content\/uploads\/sites\/215\/2019\/04\/1-94-65x6.png 65w, https:\/\/ebooks.inflibnet.ac.in\/biocp04\/wp-content\/uploads\/sites\/215\/2019\/04\/1-94-225x19.png 225w, https:\/\/ebooks.inflibnet.ac.in\/biocp04\/wp-content\/uploads\/sites\/215\/2019\/04\/1-94-350x30.png 350w\" sizes=\"auto, (max-width: 401px) 100vw, 401px\" \/><\/p>\n<ul>\n<li>The stoichiometry of TCA cycle from Acetyl CoA:<\/li>\n<\/ul>\n<p><img loading=\"lazy\" decoding=\"async\" class=\"aligncenter size-full wp-image-197\" src=\"http:\/\/biocp04.epgpbooks.inflibnet.ac.in\/wp-content\/uploads\/sites\/215\/2019\/04\/1-95.png\" alt=\"\" width=\"592\" height=\"39\" srcset=\"https:\/\/ebooks.inflibnet.ac.in\/biocp04\/wp-content\/uploads\/sites\/215\/2019\/04\/1-95.png 592w, https:\/\/ebooks.inflibnet.ac.in\/biocp04\/wp-content\/uploads\/sites\/215\/2019\/04\/1-95-300x20.png 300w, https:\/\/ebooks.inflibnet.ac.in\/biocp04\/wp-content\/uploads\/sites\/215\/2019\/04\/1-95-65x4.png 65w, https:\/\/ebooks.inflibnet.ac.in\/biocp04\/wp-content\/uploads\/sites\/215\/2019\/04\/1-95-225x15.png 225w, https:\/\/ebooks.inflibnet.ac.in\/biocp04\/wp-content\/uploads\/sites\/215\/2019\/04\/1-95-350x23.png 350w\" sizes=\"auto, (max-width: 592px) 100vw, 592px\" \/><\/p>\n<ul>\n<li>The stoichiometry of TCA cycle via Glycolysis:<\/li>\n<\/ul>\n<p><img loading=\"lazy\" decoding=\"async\" class=\"aligncenter size-full wp-image-198\" src=\"http:\/\/biocp04.epgpbooks.inflibnet.ac.in\/wp-content\/uploads\/sites\/215\/2019\/04\/1-96.png\" alt=\"\" width=\"569\" height=\"40\" srcset=\"https:\/\/ebooks.inflibnet.ac.in\/biocp04\/wp-content\/uploads\/sites\/215\/2019\/04\/1-96.png 569w, https:\/\/ebooks.inflibnet.ac.in\/biocp04\/wp-content\/uploads\/sites\/215\/2019\/04\/1-96-300x21.png 300w, https:\/\/ebooks.inflibnet.ac.in\/biocp04\/wp-content\/uploads\/sites\/215\/2019\/04\/1-96-65x5.png 65w, https:\/\/ebooks.inflibnet.ac.in\/biocp04\/wp-content\/uploads\/sites\/215\/2019\/04\/1-96-225x16.png 225w, https:\/\/ebooks.inflibnet.ac.in\/biocp04\/wp-content\/uploads\/sites\/215\/2019\/04\/1-96-350x25.png 350w\" sizes=\"auto, (max-width: 569px) 100vw, 569px\" \/><\/p>\n<ul>\n<li>The net reaction of the TCA is:<\/li>\n<\/ul>\n<p><img loading=\"lazy\" decoding=\"async\" class=\"aligncenter size-full wp-image-199\" src=\"http:\/\/biocp04.epgpbooks.inflibnet.ac.in\/wp-content\/uploads\/sites\/215\/2019\/04\/1-97.png\" alt=\"\" width=\"624\" height=\"33\" srcset=\"https:\/\/ebooks.inflibnet.ac.in\/biocp04\/wp-content\/uploads\/sites\/215\/2019\/04\/1-97.png 624w, https:\/\/ebooks.inflibnet.ac.in\/biocp04\/wp-content\/uploads\/sites\/215\/2019\/04\/1-97-300x16.png 300w, https:\/\/ebooks.inflibnet.ac.in\/biocp04\/wp-content\/uploads\/sites\/215\/2019\/04\/1-97-65x3.png 65w, https:\/\/ebooks.inflibnet.ac.in\/biocp04\/wp-content\/uploads\/sites\/215\/2019\/04\/1-97-225x12.png 225w, https:\/\/ebooks.inflibnet.ac.in\/biocp04\/wp-content\/uploads\/sites\/215\/2019\/04\/1-97-350x19.png 350w\" sizes=\"auto, (max-width: 624px) 100vw, 624px\" \/><\/p>\n<p>&nbsp;<\/p>\n<p style=\"text-align: justify\">ATP is formed from NADH and FADH2 molecules via electron transfer chain and we get 3 ATP molecules per NADH and 2 ATP molecules per FADH2. This way we get 38 ATPs from one molecule of glucose.<\/p>\n<p>&nbsp;<\/p>\n<ul>\n<li style=\"text-align: justify\">Energy calculation in kJ\/mol as 38 x 30.5 kJ\/mol = 1,160 kJ\/mol, or 40% of the theoretical maximum of 2,840 kJ\/mol available via complete oxidation of glucose.<\/li>\n<\/ul>\n<p><strong>Table 1. The stoichiometry of coenzyme reduction and ATP formation in the aerobic oxidation of a molecule of pyruvate by TCA cycle.<\/strong><\/p>\n<p>&nbsp;<\/p>\n<p><img loading=\"lazy\" decoding=\"async\" class=\"aligncenter size-full wp-image-200\" src=\"http:\/\/biocp04.epgpbooks.inflibnet.ac.in\/wp-content\/uploads\/sites\/215\/2019\/04\/1-98.png\" alt=\"\" width=\"603\" height=\"396\" srcset=\"https:\/\/ebooks.inflibnet.ac.in\/biocp04\/wp-content\/uploads\/sites\/215\/2019\/04\/1-98.png 603w, https:\/\/ebooks.inflibnet.ac.in\/biocp04\/wp-content\/uploads\/sites\/215\/2019\/04\/1-98-300x197.png 300w, https:\/\/ebooks.inflibnet.ac.in\/biocp04\/wp-content\/uploads\/sites\/215\/2019\/04\/1-98-65x43.png 65w, https:\/\/ebooks.inflibnet.ac.in\/biocp04\/wp-content\/uploads\/sites\/215\/2019\/04\/1-98-225x148.png 225w, https:\/\/ebooks.inflibnet.ac.in\/biocp04\/wp-content\/uploads\/sites\/215\/2019\/04\/1-98-350x230.png 350w\" sizes=\"auto, (max-width: 603px) 100vw, 603px\" \/><\/p>\n<p><strong>\u00a0 \u00a0 \u00a0 \u00a0 \u00a0 \u00a0 \u00a0 \u00a0 \u00a0 \u00a0 \u00a0 \u00a0 \u00a0 \u00a0 \u00a0 *This is calculated as 3 ATP per NADH and 2 ATP per FADH<\/strong><strong>2<\/strong><strong>.<\/strong><\/p>\n<p>&nbsp;<\/p>\n<p>&nbsp;<\/p>\n<p><strong>Reactions of Stoichiometry:<\/strong><\/p>\n<p>Energetic involved<\/p>\n<p>&nbsp;<\/p>\n<p>3 NADH+3H+ are formed during one turn of each cycle<\/p>\n<p>&nbsp;<\/p>\n<p style=\"text-align: justify\">Around 3 ATP formed per NADH+H+ by electron transport and oxidative phosphorylation 1 FADH2 formed during one turn of TCA cycle<\/p>\n<p>&nbsp;<\/p>\n<p>2 ATP formed per FADH2 by electron transport and oxidative phosphorylation<\/p>\n<p>&nbsp;<\/p>\n<p style=\"text-align: justify\">1 GTP are formed per turn (equivalent to 1 ATP) (during succinate thiokinase step) Total equivalent of 12 ATP formed during each turn of TCA cycle<\/p>\n<p>&nbsp;<\/p>\n<p>2 turns required for 2 acetyl-CoA&#8217;s results in an equivalent of 24 ATP\/2 acetyl-CoA<\/p>\n<p>&nbsp;<\/p>\n<p>&nbsp;<\/p>\n<p>&nbsp;<\/p>\n<p><strong>Table 2. Stoichiometry of TCA by che mical equation, enzyme responsible for it and free energy release or gain in kJ\/mol.<\/strong><\/p>\n<p>&nbsp;<\/p>\n<p><img loading=\"lazy\" decoding=\"async\" class=\"aligncenter size-full wp-image-201\" src=\"http:\/\/biocp04.epgpbooks.inflibnet.ac.in\/wp-content\/uploads\/sites\/215\/2019\/04\/1-99.png\" alt=\"\" width=\"617\" height=\"527\" srcset=\"https:\/\/ebooks.inflibnet.ac.in\/biocp04\/wp-content\/uploads\/sites\/215\/2019\/04\/1-99.png 617w, https:\/\/ebooks.inflibnet.ac.in\/biocp04\/wp-content\/uploads\/sites\/215\/2019\/04\/1-99-300x256.png 300w, https:\/\/ebooks.inflibnet.ac.in\/biocp04\/wp-content\/uploads\/sites\/215\/2019\/04\/1-99-65x56.png 65w, https:\/\/ebooks.inflibnet.ac.in\/biocp04\/wp-content\/uploads\/sites\/215\/2019\/04\/1-99-225x192.png 225w, https:\/\/ebooks.inflibnet.ac.in\/biocp04\/wp-content\/uploads\/sites\/215\/2019\/04\/1-99-350x299.png 350w\" sizes=\"auto, (max-width: 617px) 100vw, 617px\" \/><\/p>\n<ul>\n<li style=\"text-align: justify\">Moreover, organic\u00a0 substrates\u00a0 serves\u00a0 as\u00a0 source\u00a0 for\u00a0 reducing\u00a0 hydrogens\u00a0 in\u00a0 the mitochondria. Pyruvic acid is completely oxidizedwith<span style=\"text-align: initial;font-size: 1em\"> production of 10 reducing hydrogen ions (4 NADH\/H \u00f7 and 1 FADH2), is able to reduce 2.5 O2 with <\/span>formation<span style=\"text-align: initial;font-size: 1em\"> of 5 H20. In <\/span>theoretically ,<span style=\"text-align: initial;font-size: 1em\"> the equation for pyruvic acid oxidation looks nonstoichiometric with 6 H missing<\/span><\/li>\n<\/ul>\n<p><img loading=\"lazy\" decoding=\"async\" class=\"aligncenter size-full wp-image-202\" src=\"http:\/\/biocp04.epgpbooks.inflibnet.ac.in\/wp-content\/uploads\/sites\/215\/2019\/04\/1-100.png\" alt=\"\" width=\"363\" height=\"26\" srcset=\"https:\/\/ebooks.inflibnet.ac.in\/biocp04\/wp-content\/uploads\/sites\/215\/2019\/04\/1-100.png 363w, https:\/\/ebooks.inflibnet.ac.in\/biocp04\/wp-content\/uploads\/sites\/215\/2019\/04\/1-100-300x21.png 300w, https:\/\/ebooks.inflibnet.ac.in\/biocp04\/wp-content\/uploads\/sites\/215\/2019\/04\/1-100-65x5.png 65w, https:\/\/ebooks.inflibnet.ac.in\/biocp04\/wp-content\/uploads\/sites\/215\/2019\/04\/1-100-225x16.png 225w, https:\/\/ebooks.inflibnet.ac.in\/biocp04\/wp-content\/uploads\/sites\/215\/2019\/04\/1-100-350x25.png 350w\" sizes=\"auto, (max-width: 363px) 100vw, 363px\" \/><\/p>\n<ul>\n<li style=\"text-align: justify\">Pyruvic acid containing only 4 H with,task will be to identify the entries for the missing hydrogen and also 3 oxygen in the form of X. However, entry<span style=\"text-align: initial;font-size: 1em\"> of three water (H2O)in the cycle would satisfy the stoichiometry.<\/span><\/li>\n<\/ul>\n<ul style=\"text-align: justify\">\n<li>Moreover, at physiological pH, pyruvate exist in anionic form. During the decarboxylation reaction catalysed by pyruvate dehydrogenase complex, pyruvate gets one proton from product in the form of hydroxyethyl.<\/li>\n<\/ul>\n<ul>\n<li style=\"text-align: justify\">Hence, pyruvate contributes for \u201ceffective number\u201dof 4H like pyruvic acid. Referring only to the cycle, the correct stoichiometry of acetyl CoA oxidation will be as follows:<\/li>\n<\/ul>\n<p><img loading=\"lazy\" decoding=\"async\" class=\"aligncenter size-full wp-image-203\" src=\"http:\/\/biocp04.epgpbooks.inflibnet.ac.in\/wp-content\/uploads\/sites\/215\/2019\/04\/1-101.png\" alt=\"\" width=\"453\" height=\"29\" srcset=\"https:\/\/ebooks.inflibnet.ac.in\/biocp04\/wp-content\/uploads\/sites\/215\/2019\/04\/1-101.png 453w, https:\/\/ebooks.inflibnet.ac.in\/biocp04\/wp-content\/uploads\/sites\/215\/2019\/04\/1-101-300x19.png 300w, https:\/\/ebooks.inflibnet.ac.in\/biocp04\/wp-content\/uploads\/sites\/215\/2019\/04\/1-101-65x4.png 65w, https:\/\/ebooks.inflibnet.ac.in\/biocp04\/wp-content\/uploads\/sites\/215\/2019\/04\/1-101-225x14.png 225w, https:\/\/ebooks.inflibnet.ac.in\/biocp04\/wp-content\/uploads\/sites\/215\/2019\/04\/1-101-350x22.png 350w\" sizes=\"auto, (max-width: 453px) 100vw, 453px\" \/><\/p>\n<ul>\n<li>Since the process yields 8 reducing equivalents (3 NADH\/ H + + 1 FADH2).<\/li>\n<\/ul>\n<ul>\n<li style=\"text-align: justify\">According to Lenhinger, the net reaction of stoichiometry of TCAwould involve anaccess of 7 H and anwithdrawal of 9 H:<\/li>\n<\/ul>\n<p><img loading=\"lazy\" decoding=\"async\" class=\"aligncenter size-full wp-image-204\" src=\"http:\/\/biocp04.epgpbooks.inflibnet.ac.in\/wp-content\/uploads\/sites\/215\/2019\/04\/1-102.png\" alt=\"\" width=\"615\" height=\"51\" srcset=\"https:\/\/ebooks.inflibnet.ac.in\/biocp04\/wp-content\/uploads\/sites\/215\/2019\/04\/1-102.png 615w, https:\/\/ebooks.inflibnet.ac.in\/biocp04\/wp-content\/uploads\/sites\/215\/2019\/04\/1-102-300x25.png 300w, https:\/\/ebooks.inflibnet.ac.in\/biocp04\/wp-content\/uploads\/sites\/215\/2019\/04\/1-102-65x5.png 65w, https:\/\/ebooks.inflibnet.ac.in\/biocp04\/wp-content\/uploads\/sites\/215\/2019\/04\/1-102-225x19.png 225w, https:\/\/ebooks.inflibnet.ac.in\/biocp04\/wp-content\/uploads\/sites\/215\/2019\/04\/1-102-350x29.png 350w\" sizes=\"auto, (max-width: 615px) 100vw, 615px\" \/><\/p>\n<ul>\n<li style=\"text-align: justify\">H2O molecules involved in the reaction catalysed by citrate synthetase (aldol bond formation) and Fumarase (addition of H2O to form malate) serves as source for additional stoichiometric 4H hydrogens in pyruvate oxidation.<\/li>\n<\/ul>\n<ul>\n<li style=\"text-align: justify\">In fact, this H2O enters indirectly via the cleavage of Succinyl-CoA thioester equivalent to a hydrolysis reaction without the intervention of molecular H2O.<\/li>\n<\/ul>\n<ul>\n<li style=\"text-align: justify\">The cleavage of the thioester occurs through a phospholysis of a H2O equivalent from of orthophosphate. This step offersthe<span style=\"text-align: initial;font-size: 1em\"> drop of free energy needed for the ATP phosphorylation. This is equivalent to removal of H2Oinvolved in <\/span>ATPsynthesis<span style=\"text-align: initial;font-size: 1em\"> during oxidative phosphorylation.<\/span><\/li>\n<\/ul>\n<ul>\n<li>Thus, this extra H2O entering the Krebs cycle is carried by phosphate.<\/li>\n<\/ul>\n<p>&nbsp;<\/p>\n<p>&nbsp;<\/p>\n<p style=\"text-align: justify\"><strong>Table 3.Represent stoichiometry of TCA by a requirement of Prosthetic group, type of reaction and energy release or gain in kcal\/mol and kJ\/mol (Adapted from &#8211; Biochemistry 5th edition by Berg JM, Tymoczko JL<\/strong>, <strong>Stryer L)<\/strong><\/p>\n<p>&nbsp;<\/p>\n<p><img loading=\"lazy\" decoding=\"async\" class=\"aligncenter size-full wp-image-205\" src=\"http:\/\/biocp04.epgpbooks.inflibnet.ac.in\/wp-content\/uploads\/sites\/215\/2019\/04\/1-103.png\" alt=\"\" width=\"554\" height=\"541\" srcset=\"https:\/\/ebooks.inflibnet.ac.in\/biocp04\/wp-content\/uploads\/sites\/215\/2019\/04\/1-103.png 554w, https:\/\/ebooks.inflibnet.ac.in\/biocp04\/wp-content\/uploads\/sites\/215\/2019\/04\/1-103-300x293.png 300w, https:\/\/ebooks.inflibnet.ac.in\/biocp04\/wp-content\/uploads\/sites\/215\/2019\/04\/1-103-65x63.png 65w, https:\/\/ebooks.inflibnet.ac.in\/biocp04\/wp-content\/uploads\/sites\/215\/2019\/04\/1-103-225x220.png 225w, https:\/\/ebooks.inflibnet.ac.in\/biocp04\/wp-content\/uploads\/sites\/215\/2019\/04\/1-103-350x342.png 350w\" sizes=\"auto, (max-width: 554px) 100vw, 554px\" \/><\/p>\n<p>&nbsp;<\/p>\n<p><strong>Regulation of stoichiometry of the TCA<\/strong><\/p>\n<ul>\n<li style=\"text-align: justify\">The TCA must be optimally regulated by the cell. The uncontrolled TCA could led toproduction of very big amount of metabolic energy and wastage in form of ATP.<\/li>\n<\/ul>\n<ul>\n<li style=\"text-align: justify\">If the TCA cycle go slowly then the formation of ATP also too slow which help the cell to sustain. There are three irreversible reactions catalysed<span style=\"text-align: initial;font-size: 1em\"> by citrate synthase, isocitrate dehydrogenase and \u03b1-ketoglutarate dehydrogenase function <\/span>withhigher<span style=\"text-align: initial;font-size: 1em\"> -D G\u00a0<\/span>value<span style=\"text-align: initial;font-size: 1em\"> in <\/span>mitochondrial<span style=\"text-align: initial;font-size: 1em\"> matrix at high concentrations of products and reactants. The <\/span>TCAcycle<span style=\"text-align: initial;font-size: 1em\"> is linked to oxygen consumption for the regeneration of NAD+<\/span>,TCA<span style=\"text-align: initial;font-size: 1em\"> cycle is regulated by feedback inhibition.<\/span><\/li>\n<\/ul>\n<ul>\n<li>The TCA is regulated by three simple mechanisms.<\/li>\n<\/ul>\n<p style=\"text-align: justify\">\u00a0 \u00a0 (i) Availability of substrate<\/p>\n<p style=\"text-align: justify\">(ii) Inhibition by end product formed<\/p>\n<p>&nbsp;<\/p>\n<ul>\n<li style=\"text-align: justify\">Competitive feedback inhibition. Molecules such as acetyl-CoA, Succinyl-CoA, ATP, ADP, AMP, NAD+ and NADH serve as the allosteric effectors<\/li>\n<\/ul>\n<ul style=\"text-align: justify\">\n<li>In the TCA cycle all regulatory enzymes also include pyruvate dehydrogenase are allosterically inhibited by NADH and ATP.<\/li>\n<\/ul>\n<ul>\n<li style=\"text-align: justify\">The TCA\u00a0 cycle operated\u00a0 based\u00a0 on signal of\u00a0 high ratios\u00a0 of either\u00a0 ADP\/ATP\u00a0 or NAD+\/NADH which based on requirement<span style=\"text-align: initial;font-size: 1em\"> of <\/span>concentration<span style=\"text-align: initial;font-size: 1em\"> of NADH or ATP in the cell.<\/span><\/li>\n<\/ul>\n<p>&nbsp;<\/p>\n<table>\n<tbody>\n<tr>\n<td><strong>you can view video on Stoichiometry of Citric Acid Cycle<\/strong><\/td>\n<td><a href=\"https:\/\/youtu.be\/26LjokJoAYAe\" target=\"_blank\" rel=\"noopener\"><img loading=\"lazy\" decoding=\"async\" class=\"alignnone wp-image-120\" src=\"http:\/\/epgpbooks.inflibnet.ac.in\/wp-content\/uploads\/2018\/11\/download.png\" alt=\"\" width=\"36\" height=\"36\" \/><\/a><\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n<p>&nbsp;<\/p>\n<p>&nbsp;<\/p>\n<div class=\"textbox learning-objectives\">\n<h3>References<\/h3>\n<ul>\n<li style=\"text-align: justify\">Koivunen P, Hirsil\u00e4 M, Remes AM, Hassinen IE, Kivirikko KI, Myllyharju J (February 2007). &#8220;Inhibition of hypoxia-inducible factor (HIF) hydroxylases by citric acid cycle intermediates: possible links between cell metabolism and stabilization of HIF&#8221;. J. Biol. Chem. 282 (7): 4524\u201332. doi:10.1074\/jbc.M610415200. PMID 17182618<\/li>\n<li style=\"text-align: justify\">Madeira, V. M. C. (1988), Stoichiometry of reducing equivalents and splitting of water in the citric acid cycle. Biochemical Education, 16: 94\u201396.<\/li>\n<li style=\"text-align: justify\">H.A. Krebs and W.A. Johnson. 1937. The role of citric acid in intermediate metabolism in animal tissues <em>Enzymologia<\/em>4:148-156.<\/li>\n<li style=\"text-align: justify\">H.A. Krebs. 1970. The history of the tricarboxylic acid cycle <em>Perspect. Biol. Med.<\/em> 14: 154-170. (PubMed)<\/li>\n<li style=\"text-align: justify\">Krebs, H. A., and Martin, A., 1981. <em>Reminiscences and Reflections.<\/em> Clarendon Press.<\/li>\n<\/ul>\n<p>&nbsp;<\/p>\n<p><strong>Web site<\/strong><\/p>\n<ul>\n<li><a href=\"http:\/\/www.ncbi.nlm.nih.gov\/books\/NBK22427\/\">http:\/\/www.ncbi.nlm.nih.gov\/books\/NBK22427\/<\/a><\/li>\n<li><a href=\"http:\/\/oregonstate.edu\/dept\/biochem\/hhmi\/hhmiclasses\/bb451\/lectnoteskga\/citricacidcycle.html\">http:\/\/oregonstate.edu\/dept\/biochem\/hhmi\/hhmiclasses\/bb451\/lectnoteskga\/citric<\/a><a style=\"text-align: initial;text-indent: 1em;font-size: 1em\" href=\"http:\/\/oregonstate.edu\/dept\/biochem\/hhmi\/hhmiclasses\/bb451\/lectnoteskga\/citricacidcycle.html\">acidcycle.html<\/a><\/li>\n<li><a href=\"http:\/\/web.campbell.edu\/faculty\/nemecz\/323_lect\/citric_acid\/stoichiometry.html\">http:\/\/web.campbell.edu\/faculty\/nemecz\/323_lect\/citric_acid\/stoichiometry.html<\/a><\/li>\n<li><a href=\"https:\/\/www.tamu.edu\/faculty\/bmiles\/lectures\/regulationtca.pdf\">https:\/\/www.tamu.edu\/faculty\/bmiles\/lectures\/regulationtca.pdf<\/a><\/li>\n<\/ul>\n<p>&nbsp;<\/p>\n<p><strong>Books<\/strong><\/p>\n<ul>\n<li style=\"text-align: justify\">Harper\u2019sIllustrated Biochemistry by Robert K.. Murray, Daryl K. Granner, Peter A. Mayes, 26th Edition (2003)<\/li>\n<li style=\"text-align: justify\">Lehninger\u2019S Principle of Biochemistry David L. Nelson and Michael M. Cox,5th Edition (2008)<\/li>\n<li style=\"text-align: justify\">Biochemisty by Berg JM,TymoczkoJL,Stryer L, 5th edition. Publisher New York: W H Freeman; 2002.<\/li>\n<\/ul>\n<\/div>\n<p>&nbsp;<\/p>\n","protected":false},"author":3,"menu_order":12,"template":"","meta":{"pb_show_title":"on","pb_short_title":"","pb_subtitle":"","pb_authors":["dr-padma-ambalam"],"pb_section_license":""},"chapter-type":[],"contributor":[60],"license":[],"class_list":["post-194","chapter","type-chapter","status-publish","hentry","contributor-dr-padma-ambalam"],"part":3,"_links":{"self":[{"href":"https:\/\/ebooks.inflibnet.ac.in\/biocp04\/wp-json\/pressbooks\/v2\/chapters\/194","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/ebooks.inflibnet.ac.in\/biocp04\/wp-json\/pressbooks\/v2\/chapters"}],"about":[{"href":"https:\/\/ebooks.inflibnet.ac.in\/biocp04\/wp-json\/wp\/v2\/types\/chapter"}],"author":[{"embeddable":true,"href":"https:\/\/ebooks.inflibnet.ac.in\/biocp04\/wp-json\/wp\/v2\/users\/3"}],"version-history":[{"count":5,"href":"https:\/\/ebooks.inflibnet.ac.in\/biocp04\/wp-json\/pressbooks\/v2\/chapters\/194\/revisions"}],"predecessor-version":[{"id":210,"href":"https:\/\/ebooks.inflibnet.ac.in\/biocp04\/wp-json\/pressbooks\/v2\/chapters\/194\/revisions\/210"}],"part":[{"href":"https:\/\/ebooks.inflibnet.ac.in\/biocp04\/wp-json\/pressbooks\/v2\/parts\/3"}],"metadata":[{"href":"https:\/\/ebooks.inflibnet.ac.in\/biocp04\/wp-json\/pressbooks\/v2\/chapters\/194\/metadata\/"}],"wp:attachment":[{"href":"https:\/\/ebooks.inflibnet.ac.in\/biocp04\/wp-json\/wp\/v2\/media?parent=194"}],"wp:term":[{"taxonomy":"chapter-type","embeddable":true,"href":"https:\/\/ebooks.inflibnet.ac.in\/biocp04\/wp-json\/pressbooks\/v2\/chapter-type?post=194"},{"taxonomy":"contributor","embeddable":true,"href":"https:\/\/ebooks.inflibnet.ac.in\/biocp04\/wp-json\/wp\/v2\/contributor?post=194"},{"taxonomy":"license","embeddable":true,"href":"https:\/\/ebooks.inflibnet.ac.in\/biocp04\/wp-json\/wp\/v2\/license?post=194"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}