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{{chembox {{chembox
| Watchedfields = changed
| verifiedrevid = 446045728
| verifiedrevid = 455157745
| Name = <small>L</small>-Isoleucine
| ImageFileL1 = L-Isoleucin - L-Isoleucine.svg | Name = {{sm|l}}-Isoleucine
| ImageFile1 = L-Isoleucin - L-Isoleucine.svg
| ImageSizeL1 = 120px
| ImageNameL1 = Chemical structure of Isoleucine | ImageName1 = Chemical structure of Isoleucine
| ImageFileR1 = L-isoleucine-3D-balls.png | ImageCaption1 = ] of <small>L</small>-isoleucine
| ImageFileL2 = Isoleucine-from-xtal-3D-bs-17.png
| ImageSizeR1 = 120px
| ImageNameR1 = Chemical structure of Isoleucine | ImageNameL2 = Ball-and-stick model of L-isoleucine
| ImageCaptionL2 = ]
| ImageFileR2 = Isoleucine-from-xtal-3D-sf.png
| ImageNameR2 = Space-filling model of L-isoleucine
| ImageCaptionR2 = ]
| IUPACName = Isoleucine | IUPACName = Isoleucine
| OtherNames = 2-Amino-3-methylpentanoic acid | OtherNames = (2''S'',3''S'')-2-amino-3-methylpentanoic acid
| Section1 = {{Chembox Identifiers | Section1 = {{Chembox Identifiers
| IUPHAR_ligand = 3311
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}} | ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID = 6067 | ChemSpiderID = 6067
Line 23: Line 28:
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}} | StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
| StdInChIKey = AGPKZVBTJJNPAG-WHFBIAKZSA-N | StdInChIKey = AGPKZVBTJJNPAG-WHFBIAKZSA-N
| CASNo = 73-32-5 | CASNo = 73-32-5
| CASNo_Ref = {{cascite|correct|CAS}} | CASNo_Ref = {{cascite|correct|CAS}}
| CASNo1 = 443-79-8
| CASNo1_Comment = D enantiomer
| CASNo2 = 319-78-8
| CASNo2_Comment = racemic
| PubChem = 791 | PubChem = 791
| DrugBank_Ref = {{drugbankcite|correct|drugbank}} | DrugBank_Ref = {{drugbankcite|correct|drugbank}}
Line 31: Line 40:
| ChEBI = 58045 | ChEBI = 58045
| SMILES = CC(C)(C(=O)O)N | SMILES = CC(C)(C(=O)O)N
| SMILES1 = CC(C)(C(=O))
| SMILES1_Comment = ]
}} }}
| Section2 = {{Chembox Properties | Section2 = {{Chembox Properties
| C =6 | H =13 | N =1 | O=2 | C =6 | H =13 | N =1 | O=2
| MagSus = −84.9·10<sup>−6</sup> cm<sup>3</sup>/mol
}} }}
}} }}


'''Isoleucine''' (symbol '''Ile''' or '''I''')<ref>{{cite journal | vauthors = | title = IUPAC-IUB Joint Commission on Biochemical Nomenclature (JCBN). Nomenclature and symbolism for amino acids and peptides. Recommendations 1983 | journal = The Biochemical Journal | volume = 219 | issue = 2 | pages = 345–373 | date = April 1984 | pmid = 6743224 | pmc = 1153490 | doi = 10.1042/bj2190345 }}</ref> is an ] that is used in the ] of ]. It contains an ] (which is in the protonated −NH<sup>+</sup><sub>3</sub> form under biological conditions), an ] (which is in the deprotonated −COO<sup>−</sup> form under biological conditions), and a ] side chain with a ] (a central ] atom bound to three other carbon atoms). It is classified as a non-polar, uncharged (at physiological pH), branched-chain, ] amino acid. It is ] 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.<ref>{{cite journal | vauthors = Joshi V, Joung JG, Fei Z, Jander G | title = Interdependence of threonine, methionine and isoleucine metabolism in plants: accumulation and transcriptional regulation under abiotic stress | journal = Amino Acids | volume = 39 | issue = 4 | pages = 933–947 | date = October 2010 | pmid = 20186554 | doi = 10.1007/s00726-010-0505-7 | s2cid = 22641155 }}</ref> In plants and bacteria, isoleucine is synthesized from a ] employing leucine biosynthesis enzymes.<ref>{{cite journal | vauthors = Kisumi M, Komatsubara S, Chibata I | title = Pathway for isoleucine formation form pyruvate by leucine biosynthetic enzymes in leucine-accumulating isoleucine revertants of Serratia marcescens | journal = Journal of Biochemistry | volume = 82 | issue = 1 | pages = 95–103 | date = July 1977 | pmid = 142769 | doi = 10.1093/oxfordjournals.jbchem.a131698 }}</ref> It is ] by the ] AUU, AUC, and AUA.
'''Isoleucine''' (abbreviated as '''ilu''' or '''I''')<ref>{{cite web | author=IUPAC-IUBMB Joint Commission on Biochemical Nomenclature | title=Nomenclature and Symbolism for Amino Acids and Peptides | work=Recommendations on Organic & Biochemical Nomenclature, Symbols & Terminology etc | url=http://www.chem.qmul.ac.uk/iupac/AminoAcid/ | accessdate=2007-05-17}}</ref> is an α-] with the ] HO<sub>2</sub>CCH(NH<sub>2</sub>)CH(CH<sub>3</sub>)CH<sub>2</sub>CH<sub>3</sub>. It is an ], which means that humans cannot synthesize it, so it must be ingested. Its ] are AUU, AUC and AUA.


== Metabolism ==
With a hydrocarbon side chain, isoleucine is classified as a ] amino acid. Together with ], isoleucine is one of two common amino acids that have a ] side chain. Four ]s of isoleucine are possible, including two possible ]s of <small>L</small>-isoleucine. However, isoleucine present in nature exists in one enantiomeric form, (2''S'',3''S'')-2-amino-3-methylpentanoic acid.


== Biosynthesis == === Biosynthesis ===
As an essential amino acid, isoleucine is not synthesized in animals, hence it must be ingested, usually as a component of proteins. In plants and microorganisms, it is synthesized via several steps, starting from ] and ]. Enzymes involved in this biosynthesis include:<ref>Nelson, D. L.; Cox, M. M. "Lehninger, Principles of Biochemistry" 3rd Ed. Worth Publishing: New York, 2000. ISBN 1-57259-153-6.</ref> In plants and microorganisms, isoleucine is synthesized from ] and ]. This pathway is not present in humans. Enzymes involved in this biosynthesis include:<ref name="Lehninger_2000">{{Cite book | vauthors = Lehninger AL, Nelson DL, Cox MM |url=https://www.worldcat.org/oclc/42619569 |title=Lehninger principles of biochemistry. |date=2000 |publisher=Worth Publishers |isbn=1-57259-153-6 |edition=3rd |location=New York |oclc=42619569}}</ref>
# ] (also known as acetohydroxy acid synthase) # ] (also known as acetohydroxy acid synthase)
# ] # ]
Line 48: Line 60:
# ] # ]


== Catabolism == === Catabolism ===
Isoleucine is both a ] and a ] amino acid.<ref name="Lehninger_2000" /> After transamination with ], the carbon skeleton is oxidised and split into ] and ]. Propionyl-CoA is converted into ], a ] intermediate which can be converted into ] 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 ] or used in the synthesis of ] (hence ketogenic) or ].<ref name = "Rajendram_2015">{{Cite book |title=Branched chain amino acids in clinical nutrition
| volume = 1 |date=2015 | vauthors = Rajendram R, Preedy VR, Patel VB |isbn=978-1-4939-1923-9 |location=New York, New York | publisher = Humana |oclc=898999904}}</ref>


=== Metabolic diseases ===
Isoleucine is both a ] and a ] amino acid. After transamination with ] the carbon skeleton can be converted into either ], and fed into the ] for oxidation or conversion into ] for gluconeogenesis (hence glucogenic). It can also be converted into ] and fed into the TCA cycle by condensing with oxaloacetate to form ]. In mammals Acetyl CoA cannot be converted back to carbohydrate but can be used in the synthesis of ] or ]s, hence ketogenic.
The degradation of isoleucine is impaired in the following ]:


* ] (CMAMMA)
], sometimes referred to as ] or ], is an absolute requirement for the full catabolism of isoleucine (as well as ]). Without adequate biotin, the human body will be unable to fully break down isoleucine and leucine molecules <ref>http://www.metametrix.com/learning-center/case-studies/2004/biotin-detoxification-needs-in-cognitively-delayed-adult</ref>. This can lead to numerous physiological issues (related to muscle maintenance and protein synthesis, lipid metabolism, and fatty acid metabolism) as well as cognitive issues resulting from general metabolic pathway failure and the irritating effects of ], a byproduct of incomplete isoleucine catabolism. ] is an example of a disorder caused by incomplete catabolism of leucine.
* ] (MSUD)
* ]
* ]


== Nutritional Sources == === Insulin resistance ===
Isoleucine, like other ], is associated with insulin resistance: higher levels of isoleucine are observed in the blood of diabetic mice, rats, and humans.<ref>{{cite journal | vauthors = Lynch CJ, Adams SH | title = Branched-chain amino acids in metabolic signalling and insulin resistance | journal = Nature Reviews. Endocrinology | volume = 10 | issue = 12 | pages = 723–736 | date = December 2014 | pmid = 25287287 | pmc = 4424797 | doi = 10.1038/nrendo.2014.171 }}</ref> 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.<ref>{{cite journal | vauthors = Cummings NE, Williams EM, Kasza I, Konon EN, Schaid MD, Schmidt BA, Poudel C, Sherman DS, Yu D, Arriola Apelo SI, Cottrell SE, Geiger G, Barnes ME, Wisinski JA, Fenske RJ, Matkowskyj KA, Kimple ME, Alexander CM, Merrins MJ, Lamming DW | display-authors = 6 | title = Restoration of metabolic health by decreased consumption of branched-chain amino acids | journal = The Journal of Physiology | volume = 596 | issue = 4 | pages = 623–645 | date = February 2018 | pmid = 29266268 | pmc = 5813603 | doi = 10.1113/JP275075 }}</ref><ref name="Yu_2021">{{cite journal | vauthors = Yu D, Richardson NE, Green CL, Spicer AB, Murphy ME, Flores V, Jang C, Kasza I, Nikodemova M, Wakai MH, Tomasiewicz JL, Yang SE, Miller BR, Pak HH, Brinkman JA, Rojas JM, Quinn WJ, Cheng EP, Konon EN, Haider LR, Finke M, Sonsalla M, Alexander CM, Rabinowitz JD, Baur JA, Malecki KC, Lamming DW | display-authors = 6 | title = The adverse metabolic effects of branched-chain amino acids are mediated by isoleucine and valine | journal = Cell Metabolism | volume = 33 | issue = 5 | pages = 905–922.e6 | date = May 2021 | pmid = 33887198 | pmc = 8102360 | doi = 10.1016/j.cmet.2021.03.025 }}</ref> Reduced dietary levels of isoleucine are required for the beneficial metabolic effects of a ].<ref name="Yu_2021" /> In humans, a protein restricted diet lowers blood levels of isoleucine and decreases fasting blood glucose levels.<ref>{{cite journal | vauthors = Fontana L, Cummings NE, Arriola Apelo SI, Neuman JC, Kasza I, Schmidt BA, Cava E, Spelta F, Tosti V, Syed FA, Baar EL, Veronese N, Cottrell SE, Fenske RJ, Bertozzi B, Brar HK, Pietka T, Bullock AD, Figenshau RS, Andriole GL, Merrins MJ, Alexander CM, Kimple ME, Lamming DW | display-authors = 6 | title = Decreased Consumption of Branched-Chain Amino Acids Improves Metabolic Health | journal = Cell Reports | volume = 16 | issue = 2 | pages = 520–530 | date = July 2016 | pmid = 27346343 | pmc = 4947548 | doi = 10.1016/j.celrep.2016.05.092 }}</ref> Mice fed a low isoleucine diet are leaner, live longer, and are less frail.<ref>{{cite journal | vauthors = Green CL, Trautman ME, Chaiyakul K, Jain R, Alam YH, Babygirija R, Pak HH, Sonsalla MM, Calubag MF, Yeh CY, Bleicher A, Novak G, Liu TT, Newman S, Ricke WA, Matkowskyj KA, Ong IM, Jang C, Simcox J, Lamming DW | display-authors = 6 | title = Dietary restriction of isoleucine increases healthspan and lifespan of genetically heterogeneous mice | journal = Cell Metabolism | volume = 35 | issue = 11 | pages = 1976–1995.e6 | date = November 2023 | pmid = 37939658 | pmc = 10655617 | doi = 10.1016/j.cmet.2023.10.005 }}</ref> In humans, higher dietary levels of isoleucine are associated with greater ].<ref name="Yu_2021" />


==Functions and requirement==
Even though this amino acid is not produced in animals, it is stored in high quantities. Foods that have high amounts of isoleucine include eggs, soy protein, seaweed, turkey, chicken, lamb, cheese, and fish.<ref name="List of Foods high in Isoleucine">, List is in order of highest to lowest of per 200 Calorie serving of the food, not volume or weight.</ref>
The Food and Nutrition Board (FNB) of the U.S. ] has set Recommended Dietary Allowances (RDAs) for ] in 2002. For adults 19 years and older, 19 mg of isoleucine/kg body weight is required daily.<ref>{{Cite book |url=https://www.worldcat.org/oclc/57373786 |title=Dietary reference intakes for energy, carbohydrate, fiber, fat, fatty acids, cholesterol, protein, and amino acids |date=2005 |publisher=National Academies Press | author =Institute of Medicine. Panel on Macronutrients, Institute of Medicine. Standing Committee on the Scientific Evaluation of Dietary Reference Intakes |isbn=0-309-08537-3 |location=Washington, D.C. |oclc=57373786}}</ref>


Beside its biological role as a nutrient, isoleucine also participates in regulation of ] metabolism.<ref name = "Rajendram_2015" /> 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. ] is one of the many proteins that require isoleucine.<ref name="Honig_1967">{{cite journal | vauthors = Honig GR | title = Inhibition of synthesis of fetal hemoglobin by an isoleucine analogue | journal = The Journal of Clinical Investigation | volume = 46 | issue = 11 | pages = 1778–1784 | date = November 1967 | pmid = 4964832 | pmc = 292928 | doi = 10.1172/JCI105668 }}</ref> Isoleucine is present in the gamma chain of fetal hemoglobin and must be present for the protein to form. <ref name="Honig_1967" />
==Isomers of isoleucine==


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.<ref>{{cite journal | vauthors = Korman SH | title = Inborn errors of isoleucine degradation: a review | journal = Molecular Genetics and Metabolism | volume = 89 | issue = 4 | pages = 289–299 | date = December 2006 | pmid = 16950638 | doi = 10.1016/j.ymgme.2006.07.010 }}</ref> Mutations in isoleucine-degrading enzymes can lead to dangerous buildup of isoleucine and its toxic derivative. One example is ], a disorder that leaves people unable to breakdown isoleucine, ], and ].<ref>{{cite book | vauthors = Hassan SA, Gupta V | chapter = Maple Syrup Urine Disease |date=2023 | chapter-url = http://www.ncbi.nlm.nih.gov/books/NBK557773/ | title = StatPearls |access-date=2023-04-16 |place=Treasure Island (FL) |publisher=StatPearls Publishing |pmid=32491705 }}</ref> 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. <ref>{{cite journal | vauthors = Brunetti-Pierri N, Lanpher B, Erez A, Ananieva EA, Islam M, Marini JC, Sun Q, Yu C, Hegde M, Li J, Wynn RM, Chuang DT, Hutson S, Lee B | display-authors = 6 | title = Phenylbutyrate therapy for maple syrup urine disease | journal = Human Molecular Genetics | volume = 20 | issue = 4 | pages = 631–640 | date = February 2011 | pmid = 21098507 | pmc = 3024040 | doi = 10.1093/hmg/ddq507 }}</ref>
{| border="1" cellspacing="0" cellpadding="3" style="font-size:x-small; margin: 0 0 0 0.5em; background: #FFFFFF; border-collapse: collapse; border-color: #C0C090;"
! {{chembox header}} colspan=8| '''Forms of Isoleucine'''
|-
|style="background-color:#F3F3F3;"|''']''': || isoleucine || D-isoleucine || L-isoleucine || DL-isoleucine || allo-D-isoleucine || allo-L-isoleucine || allo-DL-isoleucine
|-
|style="background-color:#F3F3F3;"|'''Synonyms''': || || (''R'')-Isoleucine || L(+)-Isoleucine || (''R''*,''R''*)-isoleucine || || alloisoleucine ||
|-
|style="background-color:#F3F3F3;"|''']''':||{{PubChemCID|791}}||{{PubChemCID|94206}} ||{{PubChemCID|6306}} ||{{PubChemCID|76551}} || || ||
|-
|style="background-color:#F3F3F3;"|''']''':||{{EINECS|207-139-8}}||{{EINECS|206-269-2}}||{{EINECS|200-798-2}}||||{{EINECS|216-143-9}}||{{EINECS|216-142-3}}||{{EINECS|221-464-2}}
|-
|style="background-color:#F3F3F3;"|''']''':||443-79-8
| 319-78-8
| 73-32-5
|
| 1509-35-9
| 1509-34-8
| 3107-04-8
|}


Many animals and plants are dietary sources of isoleucine as a component of proteins.<ref name="Rajendram_2015" /> Foods that have high amounts of isoleucine include ], ], ], turkey, ], lamb, ], and ].


== Synthesis ==
{| class="wikitable centered" style="text-align:center"
Routes to isoleucine are numerous. One common multistep procedure starts from ] and ].<ref>{{Cite journal | vauthors = Marvel CS | veditors = Bachmann WE, Holmes DW |date=1941 |title=dl-Isoleucine |url=https://doi.org/10.15227/orgsyn.021.0060 |journal=Organic Syntheses |language=en |volume=21 |pages=60 |doi=10.15227/orgsyn.021.0060 |issn=0078-6209}}</ref> Synthetic isoleucine was first reported in 1905 by French chemists ] and Locquin.<ref>{{Cite journal | vauthors = Bouvealt L, Locquin R |date=1905 |title=Sur la synthése d'une nouvelle leucine |journal=Compt. Rend. |issue=141 |pages=115–117}}</ref>
|-
| ]&nbsp;]<br/>
|-
| <small>L</small>-isoleucine (2''S'',3''S'') and <small>D</small>-isoleucine (2''R'',3''R'')<br/>
|-
| ]&nbsp;]<br/>
|-
| <small>L</small>-''allo''-isoleucine (2''S'',3''R'') and <small>D</small>-''allo''-isoleucine (2''R'',3''S'')
|-
|}


==Synthesis== == Discovery ==
German chemist ] discovered isoleucine while studying the composition of beet-sugar molasses 1903.<ref name="Vickery_1931">{{Cite journal | vauthors = Vickery HB, Schmidt CL |date= October 1931 |title=The History of the Discovery of the Amino Acids. |journal=Chemical Reviews |language=en |volume=9 |issue=2 |pages=169–318 |doi=10.1021/cr60033a001 |issn=0009-2665}}</ref> 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.<ref name="Vickery_1931" /> Ehrlich published his own synthesis of isoleucine in 1908. <ref>{{Cite journal | vauthors = Ehrlich F |date=1908 |title=Über eine Synthese des Isoleucins |journal=Chemische Berichte |volume=41 |issue=1 |pages=1453–1458 |doi=10.1002/cber.190804101266 |issn=0365-9496|url=https://zenodo.org/record/2512647 }}</ref>
Isoleucine can be synthesized in a multistep procedure starting from ] and ].<ref>{{OrgSynth | Marvel, C. S. | title = dl-Isoleucine | collvol = 3 | collvolpages = 495 | year = 1955 | prep = cv3p0495}}</ref> Synthetic isoleucine was originally reported in 1905.<ref>Bouveault and Locquin, Compt. rend., 141, 115 (1905).</ref>


== See also ==
German chemist ] discovered isoleucine in ] in 1903.
*], the ] of isoleucine
*


==References== == References ==
{{Reflist}}
<references/>


==External links== == External links ==
*
*
* *


{{Amino acids}}

{{AminoAcids}}
{{Amino acid metabolism intermediates}} {{Amino acid metabolism intermediates}}


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Latest revision as of 19:31, 15 November 2024

l-Isoleucine
Chemical structure of Isoleucine
Skeletal formula of L-isoleucine
Ball-and-stick model of L-isoleucine
Ball-and-stick model of L-isoleucine
Ball-and-stick model
Space-filling model of L-isoleucine
Space-filling model of L-isoleucine
Space-filling model
Names
IUPAC name Isoleucine
Other names (2S,3S)-2-amino-3-methylpentanoic acid
Identifiers
CAS Number
3D model (JSmol)
ChEBI
ChemSpider
DrugBank
ECHA InfoCard 100.000.726 Edit this at Wikidata
IUPHAR/BPS
KEGG
PubChem CID
UNII
CompTox Dashboard (EPA)
InChI
  • InChI=1S/C6H13NO2/c1-3-4(2)5(7)6(8)9/h4-5H,3,7H2,1-2H3,(H,8,9)/t4-,5-/m0/s1Key: AGPKZVBTJJNPAG-WHFBIAKZSA-N
  • InChI=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-WHFBIAKZBB
SMILES
Properties
Chemical formula C6H13NO2
Molar mass 131.175 g·mol
Magnetic susceptibility (χ) −84.9·10 cm/mol
Supplementary data page
Isoleucine (data page)
Except where otherwise noted, data are given for materials in their standard state (at 25 °C , 100 kPa). checkY verify (what is  ?) Infobox references
Chemical compound

Isoleucine (symbol Ile or I) is an α-amino acid that is used in the biosynthesis of proteins. It contains an α-amino group (which is in the protonated −NH3 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. In plants and bacteria, isoleucine is synthesized from a pyruvate employing leucine biosynthesis enzymes. It is encoded by the codons AUU, AUC, and AUA.

Metabolism

Biosynthesis

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:

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

Catabolism

Isoleucine is both a glucogenic and a ketogenic amino acid. 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.

Metabolic diseases

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

Insulin resistance

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. 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. Reduced dietary levels of isoleucine are required for the beneficial metabolic effects of a low protein diet. In humans, a protein restricted diet lowers blood levels of isoleucine and decreases fasting blood glucose levels. Mice fed a low isoleucine diet are leaner, live longer, and are less frail. In humans, higher dietary levels of isoleucine are associated with greater body mass index.

Functions and requirement

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.

Beside its biological role as a nutrient, isoleucine also participates in regulation of glucose metabolism. 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. Isoleucine is present in the gamma chain of fetal hemoglobin and must be present for the protein to form.

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. 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. 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.

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

Synthesis

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

Discovery

German chemist Felix Ehrlich discovered isoleucine while studying the composition of beet-sugar molasses 1903. 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. Ehrlich published his own synthesis of isoleucine in 1908.

See also

References

  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. ^ 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. ^ 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. ^ 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. ^ 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.
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External links

Encoded (proteinogenic) amino acids
General topics
Unspecified L-amino acid
By properties
Aliphatic
Aromatic
Polar, uncharged
Positive charge (pKa)
Negative charge (pKa)
Amino acid metabolism metabolic intermediates
K→acetyl-CoA
lysine→
leucine→
tryptophan→alanine→
G
G→pyruvate→
citrate
glycine→
serine→
G→glutamate→
α-ketoglutarate
histidine→
proline→
arginine→
other
G→propionyl-CoA→
succinyl-CoA
valine→
isoleucine→
methionine→
threonine→
propionyl-CoA→
G→fumarate
phenylalanine→tyrosine→
G→oxaloacetate
Other
Cysteine metabolism
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