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Isoleucine

February 15, 2024

Isoleucine (symbol Ile or I)[1] is an α-amino acid that is used in the biosynthesis of proteins. It contains an α-amino group (which is in the protonated −NH+3 form under biological conditions), an α-carboxylic acid group (which is in the deprotonated −COO− form under biological conditions), and a hydrocarbon side chain with a branch (a central carbon atom bound to three other carbon atoms). It is classified as a non-polar, uncharged (at physiological pH), branched-chain, aliphatic amino acid. It is essential in humans, meaning the body cannot synthesize it. Essential amino acids are necessary in the human diet. In plants isoleucine can be synthesized from threonine and methionine.[2] In plants and bacteria, isoleucine is synthesized from pyruvate employing leucine biosynthesis enzymes.[3] It is encoded by the codons AUU, AUC, and AUA.

l-Isoleucine

Skeletal formula of L-isoleucine
Ball-and-stick model of L-isoleucine
Space-filling model of L-isoleucine
Names
IUPAC name
Isoleucine
Other names
(2S,3S)-2-amino-3-methylpentanoic acid
Identifiers
  • 73-32-5 Y
  • 443-79-8 D enantiomer
  • 319-78-8 racemic
3D model (JSmol)
ChEBI
  • CHEBI:58045 Y
ChemSpider
  • 6067 Y
DrugBank
  • DB00167 Y
ECHA InfoCard 100.000.726
  • 3311
KEGG
  • D00065 Y
  • 791
UNII
  • 04Y7590D77 Y
  • DTXSID1047441
  • InChI=1S/C6H13NO2/c1-3-4(2)5(7)6(8)9/h4-5H,3,7H2,1-2H3,(H,8,9)/t4-,5-/m0/s1 Y
    Key: AGPKZVBTJJNPAG-WHFBIAKZSA-N Y
  • InChI=1/C6H13NO2/c1-3-4(2)5(7)6(8)9/h4-5H,3,7H2,1-2H3,(H,8,9)/t4-,5-/m0/s1
    Key: AGPKZVBTJJNPAG-WHFBIAKZBB
  • CC[C@H](C)[C@@H](C(=O)O)N
  • Zwitterion: CC[C@H](C)[C@@H](C(=O)[O-])[NH3+]
Properties
C6H13NO2
Molar mass 131.175 g·mol−1
−84.9·10−6 cm3/mol
Supplementary data page
Isoleucine (data page)
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
Y verify (what is YN ?)

Metabolism edit

Biosynthesis edit

In plants and microorganisms, isoleucine is synthesized from pyruvate and alpha-ketobutyrate. This pathway is not present in humans. Enzymes involved in this biosynthesis include:[4]

  1. Acetolactate synthase (also known as acetohydroxy acid synthase)
  2. Acetohydroxy acid isomeroreductase
  3. Dihydroxyacid dehydratase
  4. Valine aminotransferase

Catabolism edit

Isoleucine is both a glucogenic and a ketogenic amino acid.[4] After transamination with alpha-ketoglutarate, the carbon skeleton is oxidised and split into propionyl-CoA and acetyl-CoA. Propionyl-CoA is converted into succinyl-CoA, a TCA cycle intermediate which can be converted into oxaloacetate for gluconeogenesis (hence glucogenic). In mammals acetyl-CoA cannot be converted to carbohydrate but can be either fed into the TCA cycle by condensing with oxaloacetate to form citrate or used in the synthesis of ketone bodies (hence ketogenic) or fatty acids.[5]

Metabolic diseases edit

The degradation of isoleucine is impaired in the following metabolic diseases:

Insulin resistance edit

Isoleucine, like other branched-chain amino acids, is associated with insulin resistance: higher levels of isoleucine are observed in the blood of diabetic mice, rats, and humans.[6] In diet-induced obese and insulin resistant mice, a diet with decreased levels of isoleucine (with or without the other branched-chain amino acids) results in reduced adiposity and improved insulin sensitivity.[7][8] Reduced dietary levels of isoleucine are required for the beneficial metabolic effects of a low protein diet.[8] In humans, a protein restricted diet lowers blood levels of isoleucine and decreases fasting blood glucose levels.[9] Mice fed a low isoleucine diet are leaner, live longer, and are less frail.[10] In humans, higher dietary levels of isoleucine are associated with greater body mass index.[8]

Functions and requirement edit

The Food and Nutrition Board (FNB) of the U.S. Institute of Medicine has set Recommended Dietary Allowances (RDAs) for essential amino acids in 2002. For adults 19 years and older, 19 mg of isoleucine/kg body weight is required daily.[11]

Beside its biological role as a nutrient, isoleucine also participates in regulation of glucose metabolism.[5] Isoleucine is an essential component of many proteins. As an essential amino acid, isoleucine must be ingested or protein production in the cell will be disrupted. Fetal hemoglobin is one of the many proteins that require isoleucine.[12] Isoleucine is present in the gamma chain of fetal hemoglobin and must be present for the protein to form. [12]

Genetic diseases can change the consumption requirements of isoleucine. Amino acids cannot be stored in the body. Buildup of excess amino acids will cause a buildup of toxic molecules so, humans have many pathways to degrade each amino acid when the need for protein synthesis has been met.[13] Mutations in isoleucine-degrading enzymes can lead to dangerous buildup of isoleucine and its toxic derivative. One example is maple syrup urine disease (MSUD), a disorder that leaves people unable to breakdown isoleucine, valine, and leucine.[14] People with MSUD manage their disease by a reduced intake of all three of those amino acids alongside drugs that help excrete built-up toxins. [15]

Many animals and plants are dietary sources of isoleucine as a component of proteins.[5] Foods that have high amounts of isoleucine include eggs, soy protein, seaweed, turkey, chicken, lamb, cheese, and fish.

Synthesis edit

Routes to isoleucine are numerous. One common multistep procedure starts from 2-bromobutane and diethylmalonate.[16] Synthetic isoleucine was first reported in 1905 by French chemists Bouveault and Locquin.[17]

Discovery edit

German chemist Felix Ehrlich discovered isoleucine while studying the composition of beet-sugar molasses 1903.[18] In 1907 Ehrlich carried out further studies on fibrin, egg albumin, gluten, and beef muscle in 1907. These studies verified the natural composition of isoleucine.[18] Ehrlich published his own synthesis of isoleucine in 1908. [19]

See also edit

References edit

  1. ^ "IUPAC-IUB Joint Commission on Biochemical Nomenclature (JCBN). Nomenclature and symbolism for amino acids and peptides. Recommendations 1983". The Biochemical Journal. 219 (2): 345–373. April 1984. doi:10.1042/bj2190345. PMC 1153490. PMID 6743224.
  2. ^ Joshi V, Joung JG, Fei Z, Jander G (October 2010). "Interdependence of threonine, methionine and isoleucine metabolism in plants: accumulation and transcriptional regulation under abiotic stress". Amino Acids. 39 (4): 933–947. doi:10.1007/s00726-010-0505-7. PMID 20186554. S2CID 22641155.
  3. ^ Kisumi M, Komatsubara S, Chibata I (July 1977). "Pathway for isoleucine formation form pyruvate by leucine biosynthetic enzymes in leucine-accumulating isoleucine revertants of Serratia marcescens". Journal of Biochemistry. 82 (1): 95–103. doi:10.1093/oxfordjournals.jbchem.a131698. PMID 142769.
  4. ^ a b Lehninger AL, Nelson DL, Cox MM (2000). Lehninger principles of biochemistry (3rd ed.). New York: Worth Publishers. ISBN 1-57259-153-6. OCLC 42619569.
  5. ^ a b c Rajendram R, Preedy VR, Patel VB (2015). Branched chain amino acids in clinical nutrition. Vol. 1. New York, New York: Humana. ISBN 978-1-4939-1923-9. OCLC 898999904.
  6. ^ Lynch CJ, Adams SH (December 2014). "Branched-chain amino acids in metabolic signalling and insulin resistance". Nature Reviews. Endocrinology. 10 (12): 723–736. doi:10.1038/nrendo.2014.171. PMC 4424797. PMID 25287287.
  7. ^ Cummings NE, Williams EM, Kasza I, Konon EN, Schaid MD, Schmidt BA, et al. (February 2018). "Restoration of metabolic health by decreased consumption of branched-chain amino acids". The Journal of Physiology. 596 (4): 623–645. doi:10.1113/JP275075. PMC 5813603. PMID 29266268.
  8. ^ a b c Yu D, Richardson NE, Green CL, Spicer AB, Murphy ME, Flores V, et al. (May 2021). "The adverse metabolic effects of branched-chain amino acids are mediated by isoleucine and valine". Cell Metabolism. 33 (5): 905–922.e6. doi:10.1016/j.cmet.2021.03.025. PMC 8102360. PMID 33887198.
  9. ^ Fontana L, Cummings NE, Arriola Apelo SI, Neuman JC, Kasza I, Schmidt BA, et al. (July 2016). "Decreased Consumption of Branched-Chain Amino Acids Improves Metabolic Health". Cell Reports. 16 (2): 520–530. doi:10.1016/j.celrep.2016.05.092. PMC 4947548. PMID 27346343.
  10. ^ Green CL, Trautman ME, Chaiyakul K, Jain R, Alam YH, Babygirija R, et al. (November 2023). "Dietary restriction of isoleucine increases healthspan and lifespan of genetically heterogeneous mice". Cell Metabolism. 35 (11): 1976–1995.e6. doi:10.1016/j.cmet.2023.10.005. PMC 10655617. PMID 37939658.
  11. ^ Institute of Medicine. Panel on Macronutrients, Institute of Medicine. Standing Committee on the Scientific Evaluation of Dietary Reference Intakes (2005). Dietary reference intakes for energy, carbohydrate, fiber, fat, fatty acids, cholesterol, protein, and amino acids. Washington, D.C.: National Academies Press. ISBN 0-309-08537-3. OCLC 57373786.
  12. ^ a b Honig GR (November 1967). "Inhibition of synthesis of fetal hemoglobin by an isoleucine analogue". The Journal of Clinical Investigation. 46 (11): 1778–1784. doi:10.1172/JCI105668. PMC 292928. PMID 4964832.
  13. ^ Korman SH (December 2006). "Inborn errors of isoleucine degradation: a review". Molecular Genetics and Metabolism. 89 (4): 289–299. doi:10.1016/j.ymgme.2006.07.010. PMID 16950638.
  14. ^ Hassan SA, Gupta V (2023). "Maple Syrup Urine Disease". StatPearls. Treasure Island (FL): StatPearls Publishing. PMID 32491705. Retrieved 2023-04-16.
  15. ^ Brunetti-Pierri N, Lanpher B, Erez A, Ananieva EA, Islam M, Marini JC, et al. (February 2011). "Phenylbutyrate therapy for maple syrup urine disease". Human Molecular Genetics. 20 (4): 631–640. doi:10.1093/hmg/ddq507. PMC 3024040. PMID 21098507.
  16. ^ Marvel CS (1941). Bachmann WE, Holmes DW (eds.). "dl-Isoleucine". Organic Syntheses. 21: 60. doi:10.15227/orgsyn.021.0060. ISSN 0078-6209.
  17. ^ Bouvealt L, Locquin R (1905). "Sur la synthése d'une nouvelle leucine". Compt. Rend. (141): 115–117.
  18. ^ a b Vickery HB, Schmidt CL (October 1931). "The History of the Discovery of the Amino Acids". Chemical Reviews. 9 (2): 169–318. doi:10.1021/cr60033a001. ISSN 0009-2665.
  19. ^ Ehrlich F (1908). "Über eine Synthese des Isoleucins". Chemische Berichte. 41 (1): 1453–1458. doi:10.1002/cber.190804101266. ISSN 0365-9496.

External links edit

  • Isoleucine degradation
  • Isoleucine biosynthesis

February 15, 2024
isoleucine, symbol, amino, acid, that, used, biosynthesis, proteins, contains, amino, group, which, protonated, form, under, biological, conditions, carboxylic, acid, group, which, deprotonated, form, under, biological, conditions, hydrocarbon, side, chain, wi. Isoleucine symbol Ile or I 1 is an a amino acid that is used in the biosynthesis of proteins It contains an a amino group which is in the protonated NH 3 form under biological conditions an a carboxylic acid group which is in the deprotonated COO form under biological conditions and a hydrocarbon side chain with a branch a central carbon atom bound to three other carbon atoms It is classified as a non polar uncharged at physiological pH branched chain aliphatic amino acid It is essential in humans meaning the body cannot synthesize it Essential amino acids are necessary in the human diet In plants isoleucine can be synthesized from threonine and methionine 2 In plants and bacteria isoleucine is synthesized from pyruvate employing leucine biosynthesis enzymes 3 It is encoded by the codons AUU AUC and AUA l Isoleucine Skeletal formula of L isoleucineBall and stick model of L isoleucineBall and stick model Space filling model of L isoleucineSpace filling modelNamesIUPAC name IsoleucineOther names 2S 3S 2 amino 3 methylpentanoic acidIdentifiersCAS Number 73 32 5 Y443 79 8 D enantiomer319 78 8 racemic3D model JSmol Interactive imageZwitterion Interactive imageChEBI CHEBI 58045 YChemSpider 6067 YDrugBank DB00167 YECHA InfoCard 100 000 726IUPHAR BPS 3311KEGG D00065 YPubChem CID 791UNII 04Y7590D77 YCompTox Dashboard EPA DTXSID1047441InChI InChI 1S C6H13NO2 c1 3 4 2 5 7 6 8 9 h4 5H 3 7H2 1 2H3 H 8 9 t4 5 m0 s1 YKey AGPKZVBTJJNPAG WHFBIAKZSA N YInChI 1 C6H13NO2 c1 3 4 2 5 7 6 8 9 h4 5H 3 7H2 1 2H3 H 8 9 t4 5 m0 s1Key AGPKZVBTJJNPAG WHFBIAKZBBSMILES CC C H C C H C O O NZwitterion CC C H C C H C O O NH3 PropertiesChemical formula C 6H 13N O 2Molar mass 131 175 g mol 1Magnetic susceptibility x 84 9 10 6 cm3 molSupplementary data pageIsoleucine data page Except where otherwise noted data are given for materials in their standard state at 25 C 77 F 100 kPa Y verify what is Y N Infobox references Contents 1 Metabolism 1 1 Biosynthesis 1 2 Catabolism 1 3 Metabolic diseases 1 4 Insulin resistance 2 Functions and requirement 3 Synthesis 4 Discovery 5 See also 6 References 7 External linksMetabolism editBiosynthesis edit In plants and microorganisms isoleucine is synthesized from pyruvate and alpha ketobutyrate This pathway is not present in humans Enzymes involved in this biosynthesis include 4 Acetolactate synthase also known as acetohydroxy acid synthase Acetohydroxy acid isomeroreductase Dihydroxyacid dehydratase Valine aminotransferaseCatabolism edit Isoleucine is both a glucogenic and a ketogenic amino acid 4 After transamination with alpha ketoglutarate the carbon skeleton is oxidised and split into propionyl CoA and acetyl CoA Propionyl CoA is converted into succinyl CoA a TCA cycle intermediate which can be converted into oxaloacetate for gluconeogenesis hence glucogenic In mammals acetyl CoA cannot be converted to carbohydrate but can be either fed into the TCA cycle by condensing with oxaloacetate to form citrate or used in the synthesis of ketone bodies hence ketogenic or fatty acids 5 Metabolic diseases edit The degradation of isoleucine is impaired in the following metabolic diseases Combined malonic and methylmalonic aciduria CMAMMA Maple syrup urine disease MSUD Methylmalonic acidemia Propionic acidemiaInsulin resistance edit Isoleucine like other branched chain amino acids is associated with insulin resistance higher levels of isoleucine are observed in the blood of diabetic mice rats and humans 6 In diet induced obese and insulin resistant mice a diet with decreased levels of isoleucine with or without the other branched chain amino acids results in reduced adiposity and improved insulin sensitivity 7 8 Reduced dietary levels of isoleucine are required for the beneficial metabolic effects of a low protein diet 8 In humans a protein restricted diet lowers blood levels of isoleucine and decreases fasting blood glucose levels 9 Mice fed a low isoleucine diet are leaner live longer and are less frail 10 In humans higher dietary levels of isoleucine are associated with greater body mass index 8 Functions and requirement editThe Food and Nutrition Board FNB of the U S Institute of Medicine has set Recommended Dietary Allowances RDAs for essential amino acids in 2002 For adults 19 years and older 19 mg of isoleucine kg body weight is required daily 11 Beside its biological role as a nutrient isoleucine also participates in regulation of glucose metabolism 5 Isoleucine is an essential component of many proteins As an essential amino acid isoleucine must be ingested or protein production in the cell will be disrupted Fetal hemoglobin is one of the many proteins that require isoleucine 12 Isoleucine is present in the gamma chain of fetal hemoglobin and must be present for the protein to form 12 Genetic diseases can change the consumption requirements of isoleucine Amino acids cannot be stored in the body Buildup of excess amino acids will cause a buildup of toxic molecules so humans have many pathways to degrade each amino acid when the need for protein synthesis has been met 13 Mutations in isoleucine degrading enzymes can lead to dangerous buildup of isoleucine and its toxic derivative One example is maple syrup urine disease MSUD a disorder that leaves people unable to breakdown isoleucine valine and leucine 14 People with MSUD manage their disease by a reduced intake of all three of those amino acids alongside drugs that help excrete built up toxins 15 Many animals and plants are dietary sources of isoleucine as a component of proteins 5 Foods that have high amounts of isoleucine include eggs soy protein seaweed turkey chicken lamb cheese and fish Synthesis editRoutes to isoleucine are numerous One common multistep procedure starts from 2 bromobutane and diethylmalonate 16 Synthetic isoleucine was first reported in 1905 by French chemists Bouveault and Locquin 17 Discovery editGerman chemist Felix Ehrlich discovered isoleucine while studying the composition of beet sugar molasses 1903 18 In 1907 Ehrlich carried out further studies on fibrin egg albumin gluten and beef muscle in 1907 These studies verified the natural composition of isoleucine 18 Ehrlich published his own synthesis of isoleucine in 1908 19 See also editAlloisoleucine the diasteromer of isoleucineReferences edit IUPAC IUB Joint Commission on Biochemical Nomenclature JCBN Nomenclature and symbolism for amino acids and peptides Recommendations 1983 The Biochemical Journal 219 2 345 373 April 1984 doi 10 1042 bj2190345 PMC 1153490 PMID 6743224 Joshi V Joung JG Fei Z Jander G October 2010 Interdependence of threonine methionine and isoleucine metabolism in plants accumulation and transcriptional regulation under abiotic stress Amino Acids 39 4 933 947 doi 10 1007 s00726 010 0505 7 PMID 20186554 S2CID 22641155 Kisumi M Komatsubara S Chibata I July 1977 Pathway for isoleucine formation form pyruvate by leucine biosynthetic enzymes in leucine accumulating isoleucine revertants of Serratia marcescens Journal of Biochemistry 82 1 95 103 doi 10 1093 oxfordjournals jbchem a131698 PMID 142769 a b Lehninger AL Nelson DL Cox MM 2000 Lehninger principles of biochemistry 3rd ed New York Worth Publishers ISBN 1 57259 153 6 OCLC 42619569 a b c Rajendram R Preedy VR Patel VB 2015 Branched chain amino acids in clinical nutrition Vol 1 New York New York Humana ISBN 978 1 4939 1923 9 OCLC 898999904 Lynch CJ Adams SH December 2014 Branched chain amino acids in metabolic signalling and insulin resistance Nature Reviews Endocrinology 10 12 723 736 doi 10 1038 nrendo 2014 171 PMC 4424797 PMID 25287287 Cummings NE Williams EM Kasza I Konon EN Schaid MD Schmidt BA et al February 2018 Restoration of metabolic health by decreased consumption of branched chain amino acids The Journal of Physiology 596 4 623 645 doi 10 1113 JP275075 PMC 5813603 PMID 29266268 a b c Yu D Richardson NE Green CL Spicer AB Murphy ME Flores V et al May 2021 The adverse metabolic effects of branched chain amino acids are mediated by isoleucine and valine Cell Metabolism 33 5 905 922 e6 doi 10 1016 j cmet 2021 03 025 PMC 8102360 PMID 33887198 Fontana L Cummings NE Arriola Apelo SI Neuman JC Kasza I Schmidt BA et al July 2016 Decreased Consumption of Branched Chain Amino Acids Improves Metabolic Health Cell Reports 16 2 520 530 doi 10 1016 j celrep 2016 05 092 PMC 4947548 PMID 27346343 Green CL Trautman ME Chaiyakul K Jain R Alam YH Babygirija R et al November 2023 Dietary restriction of isoleucine increases healthspan and lifespan of genetically heterogeneous mice Cell Metabolism 35 11 1976 1995 e6 doi 10 1016 j cmet 2023 10 005 PMC 10655617 PMID 37939658 Institute of Medicine Panel on Macronutrients Institute of Medicine Standing Committee on the Scientific Evaluation of Dietary Reference Intakes 2005 Dietary reference intakes for energy carbohydrate fiber fat fatty acids cholesterol protein and amino acids Washington D C National Academies Press ISBN 0 309 08537 3 OCLC 57373786 a b Honig GR November 1967 Inhibition of synthesis of fetal hemoglobin by an isoleucine analogue The Journal of Clinical Investigation 46 11 1778 1784 doi 10 1172 JCI105668 PMC 292928 PMID 4964832 Korman SH December 2006 Inborn errors of isoleucine degradation a review Molecular Genetics and Metabolism 89 4 289 299 doi 10 1016 j ymgme 2006 07 010 PMID 16950638 Hassan SA Gupta V 2023 Maple Syrup Urine Disease StatPearls Treasure Island FL StatPearls Publishing PMID 32491705 Retrieved 2023 04 16 Brunetti Pierri N Lanpher B Erez A Ananieva EA Islam M Marini JC et al February 2011 Phenylbutyrate therapy for maple syrup urine disease Human Molecular Genetics 20 4 631 640 doi 10 1093 hmg ddq507 PMC 3024040 PMID 21098507 Marvel CS 1941 Bachmann WE Holmes DW eds dl Isoleucine Organic Syntheses 21 60 doi 10 15227 orgsyn 021 0060 ISSN 0078 6209 Bouvealt L Locquin R 1905 Sur la synthese d une nouvelle leucine Compt Rend 141 115 117 a b Vickery HB Schmidt CL October 1931 The History of the Discovery of the Amino Acids Chemical Reviews 9 2 169 318 doi 10 1021 cr60033a001 ISSN 0009 2665 Ehrlich F 1908 Uber eine Synthese des Isoleucins Chemische Berichte 41 1 1453 1458 doi 10 1002 cber 190804101266 ISSN 0365 9496 External links editIsoleucine degradation Isoleucine biosynthesis Retrieved from https en wikipedia org w index php title Isoleucine amp oldid 1207097114, wikipedia, wiki, book, books, library,

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