imported>Robert Badgett |
imported>David E. Volk |
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| |chapterurl=http://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=stryer.chapter.2369 | | |chapterurl=http://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=stryer.chapter.2369 |
| |edition= |language= |publisher=W.H. Freeman |location=San Francisco |year=2002 |origyear= |pages= |quote= |isbn=0-7167-3051-0 |oclc= |doi= |url=http://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=stryer |accessdate=}}</ref> In [[aerobic organism]]s, the citric acid cycle is involved in the chemical conversion of [[carbohydrate]]s, [[fat]]s and [[protein]]s into [[carbon dioxide]] and [[water]] to generate a form of usable energy. The citric acid cycle also provides precursors for many compounds such as certain [[amino acid]]s, and some of its reactions are therefore important even in cells performing [[fermentation (biochemistry)|fermentation]]. | | |edition= |language= |publisher=W.H. Freeman |location=San Francisco |year=2002 |origyear= |pages= |quote= |isbn=0-7167-3051-0 |oclc= |doi= |url=http://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=stryer |accessdate=}}</ref> In [[aerobic organism]]s, the citric acid cycle is involved in the chemical conversion of [[carbohydrate]]s, [[fat]]s and [[protein]]s into [[carbon dioxide]] and [[water]] to generate a form of usable energy. The citric acid cycle also provides precursors for many compounds such as certain [[amino acid]]s, and some of its reactions are therefore important even in cells performing [[fermentation (biochemistry)|fermentation]]. |
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| ==Reactions==
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| {| align="center" cellpadding="3" style="border-collapse: collapse; margin-top: 15px; margin-bottom: 15px; border: 1px solid black;"
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| ! Molecule
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| ! [[Enzyme]]
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| ! Reaction type
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| ! [[Reactant]]s/<br /> [[Coenzyme]]s
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| ! [[Product (chemistry)|Product]]s/<br /> Coenzymes
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| | I. [[Citric acid|Citrate]]
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| | 1. [[Aconitase]]
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| | [[Dehydration]]
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| | [[Water|H<sub>2</sub>O]]
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| | II. ''[[cis]]''-[[Aconitic acid|Aconitate]]
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| | 2. [[Aconitase]]
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| | [[Hydration]]
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| | H<sub>2</sub>O
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| | III. [[Isocitric acid|Isocitrate]]
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| | 3. [[Isocitrate dehydrogenase]]
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| | [[Oxidation]]
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| | [[Nicotinamide adenine dinucleotide|NAD<sup>+</sup>]]
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| | NADH + [[Hydronium|H<sup>+</sup>]]
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| | IV. [[Oxalosuccinic acid|Oxalosuccinate]]
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| | 4. [[Isocitrate dehydrogenase]]
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| | [[Decarboxylation]]
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| | V. α-[[Ketoglutaric acid|Ketoglutarate]]
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| | 5. [[Alpha-ketoglutarate dehydrogenase|α-Ketoglutarate<br /> dehydrogenase]]
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| | Oxidative<br />decarboxylation
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| | NAD<sup>+</sup> +<br />[[Coenzyme A|CoA-SH]]
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| | NADH + H<sup>+</sup><br />+ [[Carbon dioxide|CO<sub>2</sub>]]
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| | VI. [[Succinyl-CoA]]
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| | 6. [[Succinyl coenzyme A synthetase|Succinyl-CoA synthetase]]
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| | [[Hydrolysis]]
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| | [[Guanosine diphosphate|GDP]]<br />+ [[Inorganic phosphate|P<sub>i</sub>]]
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| | [[Guanosine triphosphate|GTP]] +<br />CoA-SH
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| | VII. [[Succinic acid|Succinate]]
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| | 7. [[Succinate dehydrogenase]]
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| | Oxidation
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| | [[FAD]]
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| | FADH<sub>2</sub>
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| | VIII. [[Fumarate]]
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| | 8. [[Fumarase]]
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| | Addition ([[Water|H<sub>2</sub>O]])
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| | H<sub>2</sub>O
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| | IX. ''L''-[[Malic acid|Malate]]
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| | 9. [[Malate dehydrogenase]]
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| | Oxidation
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| | NAD<sup>+</sup>
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| | NADH + H<sup>+</sup>
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| | X. [[Oxaloacetic acid|Oxaloacetate]]
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| | 10. [[Citrate synthase]]
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| | [[Condensation reaction|Condensation]]
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| |}
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| The sum of all reactions in the citric acid cycle is:
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| : Acetyl-CoA + 3 NAD<sup>+</sup> + FAD + GDP + P<sub>i</sub> + 3 H<sub>2</sub>O → <br> CoA-SH + 3 NADH + H<sup>+</sup> + FADH<sub>2</sub> + GTP + 2 CO<sub>2</sub> + 3 H<sup>+</sup>
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| Two carbon atoms are [[oxidation|oxidized]] to CO<sub>2</sub>, and the energy from these reactions is stored in [[Guanosine triphosphate|GTP]] , NADH and FADH<sub>2</sub>. NADH and FADH<sub>2</sub> are [[coenzyme]]s that accept the electrons released in [[oxidation]] reactions, and are utilized in [[oxidative phosphorylation]].
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| ===A simplified view of the process:===
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| * The process begins with the oxidation of pyruvate, producing one CO<sub>2</sub>, and one acetyl-CoA.
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| * Acetyl-CoA reacts with the four carbon carboxylic acid, oxaloacetate--to form the six carbon carboxylic acid, citrate.
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| * Through a series of reactions citrate is converted back to oxaloacetate. This cycle produces:
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| **2 CO<sub>2</sub>
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| **3 NADH and 3 H<sup>+</sup>.
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| ** one FADH<sub>2</sub>.
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| ** one GTP
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| == Regulation ==
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| Many of the enzymes in the TCA cycle are regulated by [[Enzyme#Metabolic pathways and allosteric enzymes|negative feedback]] from ATP when the [[energy charge]] of the cell is high. Such enzymes include the [[pyruvate dehydrogenase]] complex that synthesises the acetyl-CoA needed for the first reaction of the TCA cycle. Also the enzymes citrate synthase, isocitrate dehydrogenase and alpha-ketoglutarate dehydrogenase, that regulate the first three steps of the TCA cycle, are inhibited by high concentrations of ATP. This regulation ensures that the TCA cycle will not oxidise excessive amounts of pyruvate and acetyl-CoA when ATP in the cell is plentiful. This type of negative regulation by ATP is by an [[allosteric]] mechanism.
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| Several enzymes are also negatively regulated when the level of reducing equivalents in a cell are high (high ratio of NADH/NAD+). This mechanism for regulation is due to [[Enzyme#Competitive inhibition|substrate inhibition]] by NADH of the enzymes that use NAD+ as a substrate. This includes both the entry point enzymes pyruvate dehydrogenase and citrate synthase.
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| == Major metabolic pathways converging on the TCA cycle ==
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| Most of the body's [[catabolic]] pathways converge on the TCA cycle, as the diagram shows. Reactions that form intermediates of the cycle are called [[anaplerotic reactions]].
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| The citric acid cycle is the second step in [[carbohydrate catabolism]] (the breakdown of sugars). [[Glycolysis]] breaks [[glucose]] (a six-carbon-molecule) down into [[pyruvate]] (a three-carbon molecule). In [[eukaryote]]s, pyruvate moves into the [[mitochondrium|mitochondria]]. It is converted into acetyl-CoA and enters the citric acid cycle.
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| In [[protein catabolism]], [[protein]]s are broken down by [[protease]] [[enzyme]]s into their constituent amino acids. These [[amino acid]]s are brought into the cells and can be a source of energy by being funnelled into the citric acid cycle.
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| In [[fat catabolism]], [[triglyceride]]s are [[hydrolysis|hydrolyzed]] to break them into [[fatty acid]]s and [[glycerol]]. In the liver the glycerol can be converted into glucose via dihydroxyacetone phosphate and glyceraldehyde-3-phosphate by way of [[gluconeogenesis]]. In many tissues, especially heart tissue, fatty acids are broken down through a process known as [[beta oxidation]] which results in acetyl-CoA which can be used in the citric acid cycle. Sometimes beta oxidation can yield propionyl CoA which can result in further glucose production by [[gluconeogenesis]] in liver.
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| The citric acid cycle is always followed by [[oxidative phosphorylation]]. This process extracts the energy from NADH and FADH<sub>2</sub>, recreating NAD<sup>+</sup> and FAD, so that the cycle can continue. The citric acid cycle itself does not use oxygen, but oxidative phosphorylation does.
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| The total energy gained from the complete breakdown of one molecule of glucose by [[glycolysis]], the citric acid cycle and [[oxidative phosphorylation]] equals about 36 ATP molecules.
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| The citric acid cycle is called an [[amphibolic]] pathway because it participates in both [[catabolism]] and [[anabolism]].
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| ==See also==
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| *[[Oxidative decarboxylation]]
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| *[[Citric acid]]
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| *[[Reverse Krebs cycle| Reverse (Reductive) Krebs cycle]]
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| ==Reference(s)==
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| <references/>
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| *Campbell, Reece: ''Biology'' (seventh edition). Benjamin Cummings, 2005.
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| ==External links==
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| *[http://www.science.smith.edu/departments/Biology/Bio231/krebs.html An animation of the citric acid cycle]
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| *[http://www.johnkyrk.com/krebs.html A more detailed tutorial animation]
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| *[http://www.pitt.edu/AFShome/j/b/jbrodsky/public/html/1820/tca.htm A citric-acid cycle self quiz flash applet]
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| *[http://www2.ufp.pt/~pedros/bq/tca.htm The chemical logic behind the citric acid cycle]
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