Citric acid

Citric acid is a weak organic acid that has the chemical formula C
6
H
8
O
7
. It occurs naturally in citrus fruits. In biochemistry, it is an intermediate in the citric acid cycle, which occurs in the metabolism of all aerobic organisms.

More than a million tons of citric acid are manufactured every year. It is used widely as an acidifier, as a flavoring and chelating agent.[7]

A citrate is a derivative of citric acid; that is, the salts, esters, and the polyatomic anion found in solution. An example of the former, a salt is trisodium citrate; an ester is triethyl citrate. When part of a salt, the formula of the citrate ion is written as C
6
H
5
O3−
7
or C
3
H
5
O(COO)3−
3
.

Citric acid
Zitronensäure - Citric acid
Citric-acid-3D-balls
Zitronensäure Kristallzucht
Names
Preferred IUPAC name
2-Hydroxypropane-1,2,3-tricarboxylic acid
Other names
Citric acid
Identifiers
3D model (JSmol)
ChEBI
ChEMBL
ChemSpider
DrugBank
ECHA InfoCard 100.000.973
EC Number 201-069-1
E number E330 (antioxidants, ...)
KEGG
RTECS number GE7350000
UNII
Properties
C6H8O7
Molar mass 192.123 g/mol (anhydrous), 210.038 g/mol (monohydrate)CID 22230 from PubChem
Appearance crystalline white solid
Odor odorless
Density 1.665 g/cm3 (anhydrous)
1.542 g/cm3 (18 °C, monohydrate)
Melting point 156 °C (313 °F; 429 K)
Boiling point 310 °C (590 °F; 583 K) decomposes from 175 °C[1]
117.43 g/100 mL (10 °C)
147.76 g/100 mL (20 °C)
180.89 g/100 mL (30 °C)
220.19 g/100 mL (40 °C)
382.48 g/100 mL (80 °C)
547.79 g/100 mL (100 °C)[2]
Solubility soluble in acetone, alcohol, ether, ethyl acetate, DMSO
insoluble in C
6
H
6
, CHCl3, CS2, toluene[1]
Solubility in ethanol 62 g/100 g (25 °C)[1]
Solubility in amyl acetate 4.41 g/100 g (25 °C)[1]
Solubility in diethyl ether 1.05 g/100 g (25 °C)[1]
Solubility in 1,4-Dioxane 35.9 g/100 g (25 °C)[1]
log P −1.64
Acidity (pKa) pKa1 = 3.13[3]
pKa2 = 4.76[3]
pKa3 = 6.39,[4] 6.40[5]
1.493–1.509 (20 °C)[2]
1.46 (150 °C)[1]
Viscosity 6.5 cP (50% aq. sol.)[2]
Structure
Monoclinic
Thermochemistry
226.51 J/(mol·K) (26.85 °C)[6]
252.1 J/(mol·K)[6]
−1548.8 kJ/mol[2]
−1960.6 kJ/mol[6]
−1972.34 kJ/mol (monohydrate)[2]
Pharmacology
A09AB04 (WHO)
Hazards
Main hazards skin and eye irritant
Safety data sheet HMDB
GHS pictograms The exclamation-mark pictogram in the Globally Harmonized System of Classification and Labelling of Chemicals (GHS)[3]
GHS signal word Warning
H319[3]
P305+351+338[3]
NFPA 704
Flammability code 1: Must be pre-heated before ignition can occur. Flash point over 93 °C (200 °F). E.g., canola oilHealth code 2: Intense or continued but not chronic exposure could cause temporary incapacitation or possible residual injury. E.g., chloroformReactivity code 0: Normally stable, even under fire exposure conditions, and is not reactive with water. E.g., liquid nitrogenSpecial hazards (white): no codeNFPA 704 four-colored diamond
1
2
0
Flash point 155 °C (311 °F; 428 K)
345 °C (653 °F; 618 K)
Explosive limits 8%[3]
Lethal dose or concentration (LD, LC):
3000 mg/kg (rats, oral)
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).

Natural occurrence and industrial production

Citrus fruits
Lemons, oranges, limes, and other citrus fruits possess high concentrations of citric acid

Citric acid exists in greater than trace amounts in a variety of fruits and vegetables, most notably citrus fruits.[8] Lemons and limes have particularly high concentrations of the acid; it can constitute as much as 8% of the dry weight of these fruits (about 47 g/l in the juices[9]).[a] The concentrations of citric acid in citrus fruits range from 0.005 mol/L for oranges and grapefruits to 0.30 mol/L in lemons and limes. Within species, these values vary depending on the cultivar and the circumstances in which the fruit was grown.

Industrial-scale citric acid production first began in 1890 based on the Italian citrus fruit industry, where the juice was treated with hydrated lime (calcium hydroxide) to precipitate calcium citrate, which was isolated and converted back to the acid using diluted sulfuric acid.[10] In 1893, C. Wehmer discovered Penicillium mold could produce citric acid from sugar. However, microbial production of citric acid did not become industrially important until World War I disrupted Italian citrus exports.

In 1917, American food chemist James Currie discovered certain strains of the mold Aspergillus niger could be efficient citric acid producers, and the pharmaceutical company Pfizer began industrial-level production using this technique two years later, followed by Citrique Belge in 1929. In this production technique, which is still the major industrial route to citric acid used today, cultures of A. niger are fed on a sucrose or glucose-containing medium to produce citric acid. The source of sugar is corn steep liquor, molasses, hydrolyzed corn starch or other inexpensive sugary solutions.[11] After the mold is filtered out of the resulting solution, citric acid is isolated by precipitating it with calcium hydroxide to yield calcium citrate salt, from which citric acid is regenerated by treatment with sulfuric acid, as in the direct extraction from citrus fruit juice.

In 1977, a patent was granted to Lever Brothers for the chemical synthesis of citric acid starting either from aconitic or isocitrate/alloisocitrate calcium salts under high pressure conditions. This produced citric acid in near quantitative conversion under what appeared to be a reverse non-enzymatic Krebs cycle reaction.[12]

In 2007, worldwide annual production stood at approximately 1,600,000 tons.[13] More than 50% of this volume was produced in China. More than 50% was used as acidity regulator in beverages, some 20% in other food applications, 20% for detergent applications and 10% for related applications other than food, such as cosmetics, pharmaceutics and in the chemical industry.

Chemical characteristics

Citric acid speciation
Speciation diagram for a 10-millimolar solution of citric acid

Citric acid was first isolated in 1784 by the chemist Carl Wilhelm Scheele, who crystallized it from lemon juice.[14][10][15] It can exist either in an anhydrous (water-free) form or as a monohydrate. The anhydrous form crystallizes from hot water, while the monohydrate forms when citric acid is crystallized from cold water. The monohydrate can be converted to the anhydrous form at about 78 °C. Citric acid also dissolves in absolute (anhydrous) ethanol (76 parts of citric acid per 100 parts of ethanol) at 15 °C. It decomposes with loss of carbon dioxide above about 175 °C.

Citric acid is normally considered to be a tribasic acid, with pKa values, extrapolated to zero ionic strength, of 5.21, 4.28 and 2.92 at 25 °C.[16] The pKa of the hydroxyl group has been found, by means of 13C NMR spectroscopy, to be 14.4.[17] The speciation diagram shows that solutions of citric acid are buffer solutions between about pH 2 and pH 8. In biological systems around pH 7, the two species present are the citrate ion and mono-hydrogen citrate ion. The SSC 20X hybridization buffer is an example in common use.[18] Tables compiled for biochemical studies[19] are available.

On the other hand, the pH of a 1 mM solution of citric acid will be about 3.2. The pH of fruit juices from citrus fruits like oranges and lemons depends on the citric acid concentration, being lower for higher acid concentration and conversely.

Acid salts of citric acid can be prepared by careful adjustment of the pH before crystallizing the compound. See, for example, sodium citrate.

The citrate ion forms complexes with metallic cations. The stability constants for the formation of these complexes are quite large because of the chelate effect. Consequently, it forms complexes even with alkali metal cations. However, when a chelate complex is formed using all three carboxylate groups, the chelate rings have 7 and 8 members, which are generally less stable thermodynamically than smaller chelate rings. In consequence, the hydroxyl group can be deprotonated, forming part of a more stable 5-membered ring, as in ammonium ferric citrate, (NH
4
)
5
Fe(C
6
H
4
O
7
)
2
·2H
2
O
.[20]

Citric acid can be esterified at one or more of the carboxylic acid functional groups on the molecule (using a variety of alcohols), to form any of a variety of mono-, di-, tri-, and mixed esters.

Biochemistry

Citric acid cycle

Citrate is an intermediate in the TCA cycle (aka TriCarboxylic Acid cycle, Krebs cycle, Szent-Györgyi — Krebs cycle), a central metabolic pathway for animals, plants and bacteria. Citrate synthase catalyzes the condensation of oxaloacetate with acetyl CoA to form citrate. Citrate then acts as the substrate for aconitase and is converted into aconitic acid. The cycle ends with regeneration of oxaloacetate. This series of chemical reactions is the source of two-thirds of the food-derived energy in higher organisms. Hans Adolf Krebs received the 1953 Nobel Prize in Physiology or Medicine for the discovery.

Some bacteria, notably E. coli, can produce and consume citrate internally as part of their TCA cycle, but are unable to use it as food because they lack the enzymes required to import it into the cell. After tens of thousand of evolution in a minimal glucose medium that also contains citrate during Richard Lenski's Long-Term Evolution Experiment, a variant E. coli evolved with the ability to grow aerobically on citrate. Zachary Blount, a student of Lenski's, and colleagues studied these "Cit+" E. coli[21][22] as a model for how novel traits evolve. They found evidence that in this case the innovation was immediately caused by a rare duplication mutation that was effective in causing the trait due to the accumulation of several prior "potentiating" mutations, the identity and effects of which are still under study. The evolution of the Cit+ trait has been considered a notable example of the role of historical contingency in evolution.

Other biological roles

Citrate can be transported out of the mitochondria and into the cytoplasm, then broken down into acetyl-CoA for fatty acid synthesis and into oxaloacetate. Citrate is a positive modulator of this conversion, and allosterically regulates the enzyme acetyl-CoA carboxylase, which is the regulating enzyme in the conversion of acetyl-CoA into malonyl-CoA (the commitment step in fatty acid synthesis). In short, citrate is transported to the cytoplasm, converted to acetyl CoA, which is converted into malonyl CoA by the acetyl CoA carboxylase, which is allosterically modulated by citrate.

High concentrations of cytosolic citrate can inhibit phosphofructokinase, the catalyst of one of the rate-limiting steps of glycolysis. This effect is advantageous: high concentrations of citrate indicate that there is a large supply of biosynthetic precursor molecules, so there is no need for phosphofructokinase to continue to send molecules of its substrate, fructose 6-phosphate, into glycolysis. Citrate acts by augmenting the inhibitory effect of high concentrations of ATP, another sign that there is no need to carry out glycolysis.[23]

Citrate is a vital component of bone, helping to regulate the size of apatite crystals.[24]

Applications

Food and drink

Lemon pepper preparation
Powdered citric acid being used to prepare lemon pepper seasoning

Because it is one of the stronger edible acids, the dominant use of citric acid is as a flavoring and preservative in food and beverages, especially soft drinks and candies.[10] Within the European Union it is denoted by E number E330. Citrate salts of various metals are used to deliver those minerals in a biologically available form in many dietary supplements. Citric acid has 247 kcal per 100 g.[25] The buffering properties of citrates are used to control pH in household cleaners and pharmaceuticals. In the United States the purity requirements for citric acid as a food additive are defined by the Food Chemicals Codex, which is published by the United States Pharmacopoeia (USP).

Citric acid can be added to ice cream as an emulsifying agent to keep fats from separating, to caramel to prevent sucrose crystallization, or in recipes in place of fresh lemon juice. Citric acid is used with sodium bicarbonate in a wide range of effervescent formulae, both for ingestion (e.g., powders and tablets) and for personal care (e.g., bath salts, bath bombs, and cleaning of grease). Citric acid sold in a dry powdered form is commonly sold in markets and groceries as "sour salt", due to its physical resemblance to table salt. It has use in culinary applications, as an alternative to vinegar or lemon juice, where a pure acid is needed.

Citric acid can be used in food coloring to balance the pH level of a normally basic dye.

Cleaning and chelating agent

Citric acid is an excellent chelating agent, binding metals by making them soluble. It is used to remove and discourage the buildup of limescale from boilers and evaporators.[10] It can be used to treat water, which makes it useful in improving the effectiveness of soaps and laundry detergents. By chelating the metals in hard water, it lets these cleaners produce foam and work better without need for water softening. Citric acid is the active ingredient in some bathroom and kitchen cleaning solutions. A solution with a six percent concentration of citric acid will remove hard water stains from glass without scrubbing. Citric acid can be used in shampoo to wash out wax and coloring from the hair.

In industry, it is used to dissolve rust from steel and passivate stainless steels.[26]

Illustrative of its chelating abilities, citric acid was the first successful eluant used for total ion-exchange separation of the lanthanides, during the Manhattan Project in the 1940s. In the 1950s, it was replaced by the far more efficient EDTA.

Cosmetics, pharmaceuticals, dietary supplements, and foods

Citric acid is widely used as an acidulant in creams, gels, and liquids of all kinds. In its use in foods and dietary supplements, it may be classified as a processing aid if the purpose it was added was for a technical or functional effect (e.g. acidulent, chelator, viscosifier, etc...) for a process. If it is still present in insignificant amounts, and the technical or functional effect is no longer present, it may be exempted from labeling <21 CFR §101.100(c)>.

Citric acid is an alpha hydroxy acid and used as an active ingredient in chemical peels.

Citric acid is commonly used as a buffer to increase the solubility of brown heroin. Single-use citric acid sachets have been used as an inducement to get heroin users to exchange their dirty needles for clean needles in an attempt to decrease the spread of HIV and hepatitis.[27]

Citric acid is used as one of the active ingredients in the production of antiviral tissues.[28]

Other uses

Citric acid is used as an odorless alternative to white vinegar for home dyeing with acid dyes.

Sodium citrate is a component of Benedict's reagent, used for identification both qualitatively and quantitatively, of reducing sugars.

Citric acid can be used as an alternative to nitric acid in passivation of stainless steel.[29]

Citric acid can be used as a lower-odor stop bath as part of the process for developing photographic film. Photographic developers are alkaline, so a mild acid is used to neutralize and stop their action quickly, but commonly used acetic acid leaves a strong vinegar odor in the darkroom.[30]

Citric acid/potassium-sodium citrate can be used as a blood acid regulator.

Soldering Flux. Citric Acid is an excellent soldering flux,[31] either dry or as a concentrated solution in water. It should be washed off after soldering, especially with fine wires, as it is mildly corrosive. It dissolves and washes off quickly in hot water.

Synthesize solid materials from small molecules

In materials science, the Citrate-gel method is a process similar to the sol-gel method, which is a method for producing solid materials from small molecules. During the synthetic process, metal salts or alkoxides are introduced into a citric acid solution. The formation of citric complexes is believed to balance the difference in individual behavior of ions in solution, which results in a better distribution of ions and prevents the separation of components at later process stages. The polycondensation of ethylene glycol and citric acid starts above 100ºС, resulting in polymer citrate gel formation.

Safety

Although a weak acid, exposure to pure citric acid can cause adverse effects. Inhalation may cause cough, shortness of breath, or sore throat. Over-ingestion may cause abdominal pain and sore throat. Exposure of concentrated solutions to skin and eyes can cause redness and pain.[32] Long-term or repeated consumption may cause erosion of tooth enamel.[32][33][34]

Compendial status

See also

References

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  2. ^ a b c d e CID 311 from PubChem
  3. ^ a b c d e f Sigma-Aldrich Co., Citric acid. Retrieved on 2014-06-02.
  4. ^ "Data for Biochemical Research". ZirChrom Separations, Inc. Retrieved January 11, 2012.
  5. ^ "Ionization Constants of Organic Acids". Michigan State University. Retrieved January 11, 2012.
  6. ^ a b c Citric acid in Linstrom, Peter J.; Mallard, William G. (eds.); NIST Chemistry WebBook, NIST Standard Reference Database Number 69, National Institute of Standards and Technology, Gaithersburg (MD), http://webbook.nist.gov (retrieved 2014-06-02)
  7. ^ Apleblat, Alexander (2014). Citric acid. Springer. ISBN 978-3-319-11232-9.
  8. ^ Template:Need proper citation
  9. ^ Penniston KL, Nakada SY, Holmes RP, Assimos DG; Nakada; Holmes; Assimos (2008). "Quantitative Assessment of Citric Acid in Lemon Juice, Lime Juice, and Commercially-Available Fruit Juice Products". Journal of Endourology. 22 (3): 567–570. doi:10.1089/end.2007.0304. PMC 2637791. PMID 18290732.CS1 maint: Multiple names: authors list (link)
  10. ^ a b c d Frank H. Verhoff, "Citric Acid", Ullmann's Encyclopedia of Industrial Chemistry, Weinheim: Wiley-VCH
  11. ^ Lotfy, Walid A.; Ghanem, Khaled M.; El-Helow, Ehab R. (2007). "Citric acid production by a novel Aspergillus niger isolate: II. Optimization of process parameters through statistical experimental designs". Bioresource Technology. 98 (18): 3470–3477. doi:10.1016/j.biortech.2006.11.032. PMID 17317159.
  12. ^ US 4056567-V.Lamberti and E.Gutierrez
  13. ^ Berovic, M.; Legisa, M. (2007). "Citric acid production". Biotechnology Annual Review Volume 13. Biotechnology Annual Review. 13. pp. 303–343. doi:10.1016/S1387-2656(07)13011-8. ISBN 9780444530325. PMID 17875481.
  14. ^ Scheele, Carl Wilhelm (1784). "Anmärkning om Citron-saft, samt sätt at crystallisera densamma" [Note about lemon juice, as well as ways to crystallize it]. Kungliga Vetenskaps Academiens Nya Handlingar [New Proceedings of the Royal Academy of Science]. 2nd series (in Swedish). 5: 105–109.
  15. ^ Graham, Thomas (1842). Elements of chemistry, including the applications of the science in the arts. Hippolyte Baillière, foreign bookseller to the Royal College of Surgeons, and to the Royal Society, 219, Regent Street. p. 944. Retrieved June 4, 2010.
  16. ^ Goldberg, Robert N.; Kishore, Nand; Lennen, Rebecca M. (2002). "Thermodynamic Quantities for the Ionization Reactions of Buffers". J. Phys. Chem. Ref. Data. 31 (1): 231–370. Bibcode:2002JPCRD..31..231G. doi:10.1063/1.1416902.
  17. ^ Silva, Andre M. N.; Kong, Xiaole; Hider, Robert C. (2009). "Determination of the pKa value of the hydroxyl group in the α-hydroxycarboxylates citrate, malate and lactate by 13C NMR: implications for metal coordination in biological systems". Biometals. 22 (5): 771–778. doi:10.1007/s10534-009-9224-5. PMID 19288211.
  18. ^ Maniatis, T.; Fritsch, E. F.; Sambrook, J. 1982. Molecular Cloning: A Laboratory Manual. Cold Spring Harbor Laboratory, Cold Spring Harbor, NY.
  19. ^ Gomori, G. (1955). "16 Preparation of buffers for use in enzyme studies". Methods in Enzymology Volume 1. Methods in Enzymology. 1. pp. 138–146. doi:10.1016/0076-6879(55)01020-3. ISBN 9780121818012.
  20. ^ Matzapetakis, M.; Raptopoulou, C. P.; Tsohos, A.; Papaefthymiou, V.; Moon, S. N.; Salifoglou, A. (1998). "Synthesis, Spectroscopic and Structural Characterization of the First Mononuclear, Water Soluble Iron−Citrate Complex, (NH4)5Fe(C6H4O7)2·2H2O". J. Am. Chem. Soc. 120 (50): 13266–13267. doi:10.1021/ja9807035.
  21. ^ Powell, Alvin (February 14, 2014). "59,000 generations of bacteria, plus freezer, yield startling results". phys.org. Retrieved April 13, 2017.
  22. ^ Blount, Z. D.; Borland, C. Z.; Lenski, R. E. (4 June 2008). "Historical contingency and the evolution of a key innovation in an experimental population of Escherichia coli" (PDF). Proceedings of the National Academy of Sciences. 105 (23): 7899–7906. Bibcode:2008PNAS..105.7899B. doi:10.1073/pnas.0803151105. PMC 2430337. PMID 18524956. Retrieved April 13, 2017.
  23. ^ Stryer, Lubert; Berg, Jeremy; Tymoczko, John (2003). "Section 16.2: The Glycolytic Pathway Is Tightly Controlled". Biochemistry (5. ed., international ed., 3. printing ed.). New York: Freeman. ISBN 978-0716746843.
  24. ^ Hu, Y.-Y.; Rawal, A.; Schmidt-Rohr, K. (December 2010). "Strongly bound citrate stabilizes the apatite nanocrystals in bone". Proceedings of the National Academy of Sciences. 107 (52): 22425–22429. Bibcode:2010PNAS..10722425H. doi:10.1073/pnas.1009219107. PMC 3012505. PMID 21127269. Retrieved July 28, 2012.
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  26. ^ https://www.astm.org/Standards/A967.htm
  27. ^ Garden, J., Roberts, K., Taylor, A., and Robinson, D. (2003). "Evaluation of the Provision of Single Use Citric Acid Sachets to Injecting Drug Users" (pdf). Scottish Center for Infection and Environmental Health.
  28. ^ "Tissues that fight germs". CNN. July 14, 2004. Retrieved May 8, 2008.
  29. ^ "Pickling and Passivating Stainless Steel" (PDF). Euro-inox.org. Archived from the original (PDF) on September 12, 2012. Retrieved 2013-01-01.
  30. ^ Anchell, Steve. "The Darkroom Cookbook: 3rd Edition (Paperback)". Focal Press. Retrieved 2013-01-01.
  31. ^ "An Investigation of the Chemistry of Citric Acid in Military Soldering Applications" (PDF). 1995-06-19.
  32. ^ a b "Citric acid". International Chemical Safety Cards. NIOSH. 2018-09-18.
  33. ^ J. Zheng, F. Xiao, L. M. Qian, Z. R. Zhou; Xiao; Qian; Zhou (December 2009). "Erosion behavior of human tooth enamel in citric acid solution". Tribology International. 42 (11–12): 1558–1564. doi:10.1016/j.triboint.2008.12.008.CS1 maint: Multiple names: authors list (link)
  34. ^ "Effect of Citric Acid on Tooth Enamel".
  35. ^ British Pharmacopoeia Commission Secretariat (2009). "Index, BP 2009" (PDF). Archived from the original (PDF) on April 11, 2009. Retrieved February 4, 2010.
  36. ^ "Japanese Pharmacopoeia, Fifteenth Edition" (PDF). 2006. Archived from the original (PDF) on July 22, 2011. Retrieved 4 February 2010.
  1. ^ This still does not make the lemon particularly strongly acidic. This is because, as a weak acid, most of the acid molecules are not dissociated so not contributing to acidity inside the lemon or its juice.
ATP citrate lyase

ATP citrate lyase is an enzyme that in animals represents an important step in fatty acid biosynthesis. ATP citrate lyase is important in that, by converting citrate to acetyl CoA, it links the metabolism of carbohydrates, which yields citrate as an intermediate, and the production of fatty acids, which requires acetyl CoA.

In plants, ATP citrate lyase generates cytosolic acetyl-CoA precursor of thousands of specialized metabolites including waxes, sterols, and polyketides.

Acetyl-CoA

Acetyl-CoA (acetyl coenzyme A) is a molecule that participates in many biochemical reactions in protein, carbohydrate and lipid metabolism. Its main function is to deliver the acetyl group to the citric acid cycle (Krebs cycle) to be oxidized for energy production. Coenzyme A (CoASH or CoA) consists of a β-mercaptoethylamine group linked to the vitamin pantothenic acid through an amide linkage and 3'-phosphorylated ADP. The acetyl group (indicated in blue in the structural diagram on the right) of acetyl-CoA is linked to the sulfhydryl substituent of the β-mercaptoethylamine group. This thioester linkage is a "high energy" bond, which is particularly reactive. Hydrolysis of the thioester bond is exergonic (−31.5 kJ/mol).

CoA is acetylated to acetyl-CoA by the breakdown of carbohydrates through glycolysis and by the breakdown of fatty acids through β-oxidation. Acetyl-CoA then enters the citric acid cycle, where the acetyl group is oxidized to carbon dioxide and water, and the energy released captured in the form of 11 ATP and one GTP per acetyl group.

Konrad Bloch and Feodor Lynen were awarded the 1964 Nobel Prize in Physiology and Medicine for their discoveries linking acetyl-CoA and fatty acid metabolism. Fritz Lipmann won the Nobel Prize in 1953 for his discovery of the cofactor coenzyme A.

Adenosine triphosphate

Adenosine triphosphate (ATP) is a complex organic chemical that provides energy to drive many processes in living cells, e.g. muscle contraction, nerve impulse propagation, and chemical synthesis. Found in all forms of life, ATP is often referred to as the "molecular unit of currency" of intracellular energy transfer. When consumed in metabolic processes, it converts either to adenosine diphosphate (ADP) or to adenosine monophosphate (AMP). Other processes regenerate ATP so that the human body recycles its own body weight equivalent in ATP each day. It is also a precursor to DNA and RNA, and is used as a coenzyme.

From the perspective of biochemistry, ATP is classified as a nucleoside triphosphate, which indicates that it consists of three components: a nitrogenous base (adenine), the sugar ribose, and the triphosphate.

Beta oxidation

In biochemistry and metabolism, beta-oxidation is the catabolic process by which fatty acid molecules are broken down in the cytosol in prokaryotes and in the mitochondria in eukaryotes to generate acetyl-CoA, which enters the citric acid cycle, and NADH and FADH2, which are co-enzymes used in the electron transport chain. It is named as such because the beta carbon of the fatty acid undergoes oxidation to a carbonyl group. Beta-oxidation is primarily facilitated by the mitochondrial trifunctional protein, an enzyme complex associated with the inner mitochondrial membrane, although very long chain fatty acids are oxidized in peroxisomes.

The overall reaction for one cycle of beta oxidation is:

Cn-acyl-CoA + FAD + NAD+ + H2O + CoA → Cn-2-acyl-CoA + FADH2 + NADH + H+ + acetyl-CoA

Buffer solution

A buffer solution (more precisely, pH buffer or hydrogen ion buffer) is an aqueous solution consisting of a mixture of a weak acid and its conjugate base, or vice versa. Its pH changes very little when a small amount of strong acid or base is added to it. Buffer solutions are used as a means of keeping pH at a nearly constant value in a wide variety of chemical applications. In nature, there are many systems that use buffering for pH regulation. For example, the bicarbonate buffering system is used to regulate the pH of blood.

Citrate synthase

The enzyme citrate synthase E.C. 2.3.3.1 (previously 4.1.3.7)] exists in nearly all living cells and stands as a pace-making enzyme in the first step of the citric acid cycle (or Krebs cycle). Citrate synthase is localized within eukaryotic cells in the mitochondrial matrix, but is encoded by nuclear DNA rather than mitochondrial. It is synthesized using cytoplasmic ribosomes, then transported into the mitochondrial matrix.

Citrate synthase is commonly used as a quantitative enzyme marker for the presence of intact mitochondria. Maximal activity of citrate synthase indicates the mitochondrial content of skeletal muscle. The maximal activity can be increased by endurance training or high-intensity interval training, but maximal activity is increased more with high-intensity interval training.Citrate synthase catalyzes the condensation reaction of the two-carbon acetate residue from acetyl coenzyme A and a molecule of four-carbon oxaloacetate to form the six-carbon citrate:

acetyl-CoA + oxaloacetate + H2O → citrate + CoA-SH

Oxaloacetate is regenerated after the completion of one round of the Krebs cycle.

Oxaloacetate is the first substrate to bind to the enzyme. This induces the enzyme to change its conformation, and creates a binding site for the acetyl-CoA. Only when this citroyl-CoA has formed will another conformational change cause thioester hydrolysis and release coenzyme A. This ensures that the energy released from the thioester bond cleavage will drive the condensation.

Citric acid cycle

The citric acid cycle (CAC) – also known as the TCA cycle (tricarboxylic acid cycle) or the Krebs cycle – is a series of chemical reactions used by all aerobic organisms to release stored energy through the oxidation of acetyl-CoA derived from carbohydrates, fats, and proteins, into adenosine triphosphate (ATP) and carbon dioxide. In addition, the cycle provides precursors of certain amino acids, as well as the reducing agent NADH, that are used in numerous other reactions. Its central importance to many biochemical pathways suggests that it was one of the earliest established components of cellular metabolism and may have originated abiogenically. Even though it is branded as a 'cycle', it is not necessary for metabolites to follow only one specific route; at least three segments of the citric acid cycle have been recognized.The name of this metabolic pathway is derived from the citric acid (a type of tricarboxylic acid, often called citrate, as the ionized form predominates at biological pH) that is consumed and then regenerated by this sequence of reactions to complete the cycle. The cycle consumes acetate (in the form of acetyl-CoA) and water, reduces NAD+ to NADH, and produces carbon dioxide as a waste byproduct. The NADH generated by the citric acid cycle is fed into the oxidative phosphorylation (electron transport) pathway. The net result of these two closely linked pathways is the oxidation of nutrients to produce usable chemical energy in the form of ATP.

In eukaryotic cells, the citric acid cycle occurs in the matrix of the mitochondrion. In prokaryotic cells, such as bacteria, which lack mitochondria, the citric acid cycle reaction sequence is performed in the cytosol with the proton gradient for ATP production being across the cell's surface (plasma membrane) rather than the inner membrane of the mitochondrion. The overall yield of energy-containing compounds from the TCA cycle is three NADH, one FADH2, and one GTP.

Fumarase

Fumarase (or fumarate hydratase) is an enzyme that catalyzes the reversible hydration/dehydration of fumarate to malate. Fumarase comes in two forms: mitochondrial and cytosolic. The mitochondrial isoenzyme is involved in the Krebs Cycle (also known as the Tricarboxylic Acid Cycle [TCA] or the Citric Acid Cycle), and the cytosolic isoenzyme is involved in the metabolism of amino acids and fumarate. Subcellular localization is established by the presence of a signal sequence on the amino terminus in the mitochondrial form, while subcellular localization in the cytosolic form is established by the absence of the signal sequence found in the mitochondrial variety.This enzyme participates in 2 metabolic pathways: citric acid cycle, reductive citric acid cycle (CO2 fixation), and is also important in renal cell carcinoma. Mutations in this gene have been associated with the development of leiomyomas in the skin and uterus in combination with renal cell carcinoma.

Fumaric acid

Fumaric acid or trans-butenedioic acid is the chemical compound with the formula HO2CCH=CHCO2H. Fumaric acid has a fruit-like taste and has been used as a food acidulant since 1946. Its E number is E297.

Isocitric acid

Isocitric acid is a structural isomer of citric acid. Salts and esters of isocitric acid are known as isocitrates. The isocitrate anion is a substrate of the citric acid cycle. Isocitrate is formed from citrate with the help of the enzyme aconitase, and is acted upon by isocitrate dehydrogenase.

Isocitric acid is commonly used as a marker to detect the authenticity and quality of fruit products, most often citrus juices. In authentic orange juice, for example, the ratio of citric acid to D-isocitric acid is usually less than 130. An isocitric acid value higher than this may be indicative of fruit juice adulteration.

Lemon

The lemon, Citrus limon (L.) Osbeck, is a species of small evergreen tree in the flowering plant family Rutaceae, native to South Asia, primarily North eastern India.

The tree's ellipsoidal yellow fruit is used for culinary and non-culinary purposes throughout the world, primarily for its juice, which has both culinary and cleaning uses. The pulp and rind (zest) are also used in cooking and baking. The juice of the lemon is about 5% to 6% citric acid, with a pH of around 2.2, giving it a sour taste. The distinctive sour taste of lemon juice makes it a key ingredient in drinks and foods such as lemonade and lemon meringue pie.

Malic acid

Malic acid is an organic compound with the molecular formula C4H6O5. It is a dicarboxylic acid that is made by all living organisms, contributes to the sour taste of fruits, and is used as a food additive. Malic acid has two stereoisomeric forms (L- and D-enantiomers), though only the L-isomer exists naturally. The salts and esters of malic acid are known as malates. The malate anion is an intermediate in the citric acid cycle.

Mitochondrial matrix

In the mitochondrion, the matrix is the space within the inner membrane. The word "matrix" stems from the fact that this space is viscous, compared to the relatively aqueous cytoplasm. The mitochondrial matrix contains the mitochondria's DNA, ribosomes, soluble enzymes, small organic molecules, nucleotide cofactors, and inorganic ions.[1] The enzymes in the matrix facilitate reactions responsible for the production of ATP, such as the citric acid cycle, oxidative phosphorylation, oxidation of pyruvate and the beta oxidation of fatty acids.The composition of the matrix based on its structures and contents produce an environment that allows the anabolic and catabolic pathways to proceed favorably for. The electron transport chain and enzymes in the matrix play a large role in the citric acid cycle and oxidative phosphorylation. The citric acid cycle produces NADH and FADH2 through oxidation that will be reduced in oxidative phosphorylation to produce ATP.The cytosolic, intermembrane space, compartment has a water content of 3.8 μl/mg protein, while the mitochondrial matrix 0.8 μl/mg protein. It is not known how mitochondria maintain osmotic balance across the inner mitochondrial membrane, although the membrane contains aquaporins that are believed to be conduits for regulated water transport. Mitochondrial matrix has a pH of about 7.8, which is higher than the pH of the inner membrane of the mitochondria, which is around 7.0-7.4. Mitochondrial DNA was discovered by Nash and Margit in 1963. One to many double stranded mainly circular DNA is present in mitochondrial matrix. Mitochondrial DNA is 1% of total DNA of a cell. It is rich in Guanine and Cytosine content. Mitochondria of mammals have 55s ribosomes.

Oxaloacetic acid

Oxaloacetic acid (also known as oxalacetic acid) is a crystalline organic compound with the chemical formula HO2CC(O)CH2CO2H. Oxaloacetic acid, in the form of its conjugate base oxaloacetate, is a metabolic intermediate in many processes that occur in animals. It takes part in gluconeogenesis, the urea cycle, the glyoxylate cycle, amino acid synthesis, fatty acid synthesis and the citric acid cycle.

Oxidative decarboxylation

Oxidative decarboxylation reactions are oxidation reactions in which a carboxylate group is removed, forming carbon dioxide. They often occur in biological systems: there are many examples in the citric acid cycle.

Oxoglutarate dehydrogenase complex

The oxoglutarate dehydrogenase complex (OGDC) or α-ketoglutarate dehydrogenase complex is an enzyme complex, most commonly known for its role in the citric acid cycle.

Pyruvate dehydrogenase

Pyruvate dehydrogenase is the first component enzyme of pyruvate dehydrogenase complex (PDC). The pyruvate dehydrogenase complex contributes to transforming pyruvate into acetyl-CoA by a process called pyruvate decarboxylation. Acetyl-CoA may then be used in the citric acid cycle to carry out cellular respiration, so pyruvate dehydrogenase contributes to linking the glycolysis metabolic pathway to the citric acid cycle and releasing energy via NADH.

Pyruvate dehydrogenase kinase

Pyruvate dehydrogenase kinase (also pyruvate dehydrogenase complex kinase, PDC kinase, or PDK; EC 2.7.11.2) is a kinase enzyme which acts to inactivate the enzyme pyruvate dehydrogenase by phosphorylating it using ATP.

PDK thus participates in the regulation of the pyruvate dehydrogenase complex of which pyruvate dehydrogenase is the first component. Both PDK and the pyruvate dehydrogenase complex are located in the mitochondrial matrix of eukaryotes. The complex acts to convert pyruvate (a product of glycolysis in the cytosol) to acetyl-coA, which is then oxidized in the mitochondria to produce energy, in the citric acid cycle. By downregulating the activity of this complex, PDK will decrease the oxidation of pyruvate in mitochondria and increase the conversion of pyruvate to lactate in the cytosol.

The opposite action of PDK, namely the dephosphorylation and activation of pyruvate dehydrogenase, is catalyzed by a phosphoprotein phosphatase called pyruvate dehydrogenase phosphatase.

(Pyruvate dehydrogenase kinase should not be confused with Phosphoinositide-dependent kinase-1, which is also sometimes known as "PDK1".)

Reverse Krebs cycle

The reverse Krebs cycle (also known as the reverse tricarboxylic acid cycle, the reverse TCA cycle, or the reverse citric acid cycle)

is a sequence of chemical reactions that are used by some bacteria to produce carbon compounds from carbon dioxide and water.

The reaction is the citric acid cycle run in reverse: Where the Krebs cycle takes complex carbon molecules in the form of sugars and oxidizes them to CO2 and water, the reverse cycle takes CO2 and water to make carbon compounds.

This process is used by some bacteria to synthesise carbon compounds, sometimes using hydrogen, sulfide, or thiosulfate as electron donors. In this process, it can be seen as an alternative to the fixation of inorganic carbon in the reductive pentose phosphate cycle which occurs in a wide variety of microbes and higher organisms.

The reaction is a possible candidate for prebiotic early-earth conditions and, so, is of interest in the research of the origin of life. It has been found that some non-consecutive steps of the cycle can be catalyzed by minerals through photochemistry, while entire two and three-step sequences can be promoted by metal ions and iron (as reducing agent) under acidic conditions.

Digestives, including enzymes (A09)
Enzymes
Acid preparations
True species
Major hybrids
True and hybrid
cultivars
Citrons
Mandarin oranges
Papedas
Pomelos
Australian and Papuan citrus
(Microcitrus, Eromocitrus,
Clymenia and Oxanthera subgenera)
Kumquat hybrids
(×Citrofortunella)
Related genera
(perhaps properly Citrus)
Drinks
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Citrus botanists
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