| Revision as of 05:31, 17 February 2012 editBeetstra (talk | contribs)Edit filter managers, Administrators172,031 edits Saving copy of the {{chembox}} taken from revid 437766225 of page Alpha-Ketoisocaproic_acid for the Chem/Drugbox validation project (updated: ''). |
Latest revision as of 20:04, 31 October 2024 edit KormiSK (talk | contribs)Extended confirmed users919 editsmNo edit summaryTag: Visual edit: Switched |
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{{lowercase title}} |
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{{ambox | text = This page contains a copy of the infobox ({{tl|chembox}}) taken from revid of page ] with values updated to verified values.}} |
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{{Chembox |
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{{Chembox |
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| Watchedfields = changed |
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| verifiedrevid = 411952246 |
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| verifiedrevid = 477319228 |
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| Name = α-Ketoisocaproic acid |
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| Name = α-Ketoisocaproic acid |
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| ImageFile = Alpha-ketoisocaproic acid.png |
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| ImageFile = Alpha-ketoisocaproic acid.png |
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| ImageFile_Ref = {{chemboximage|correct|??}} |
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| ImageFile_Ref = {{chemboximage|correct|??}} |
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| ImageSize = 244 |
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| ImageSize = 244 |
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| ImageName = Skeletal formula of ''alpha''-ketoisocaproic acid |
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| ImageName = Skeletal formula of ''alpha''-ketoisocaproic acid |
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| IUPACName = 4-Methyl-2-oxopentanoic acid |
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| IUPACName = 4-Methyl-2-oxopentanoic acid |
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| SystematicName = 4-Methyl-2-oxopentanoic acid<ref>http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=70</ref> |
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| SystematicName = 4-Methyl-2-oxopentanoic acid<ref>{{PubChem|70}}</ref> |
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| OtherNames = 4-Methyl-2-oxovaleric acid<br>2-Ketoisocaproic acid<br>2-Oxo-4-methylpentanoic acid<br>2-Oxo-4-methylvaleric acid<br>2-Oxoisocaproic acid<br>2-Oxoleucine<br>Isobutylglyoxylic acid<br>Ketoleucine<br>α-Ketoisocapronic acid<br>α-Oxoisocaproic acid |
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| OtherNames = 4-Methyl-2-oxovaleric acid |
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| Section1 = {{Chembox Identifiers |
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|Section1={{Chembox Identifiers |
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| IUPHAR_ligand = 4656 |
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| CASNo = 816-66-0 |
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| CASNo_Ref = {{cascite|correct|CAS}} |
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| CASNo = 816-66-0 |
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| CASNo_Ref = {{cascite|correct|CAS}} |
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| UNII_Ref = {{fdacite|correct|FDA}} |
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| PubChem = 70 |
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| UNII = 4GUJ8AH400 |
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| PubChem_Ref = {{Pubchemcite|correct|PubChem}} |
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| ChemSpiderID = 69 |
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| PubChem = 70 |
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| ChemSpiderID = 69 |
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| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}} |
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| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}} |
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| EINECS = 212-435-5 |
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| UNNumber = 3265 |
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| EINECS = 212-435-5 |
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| DrugBank = DB03229 |
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| UNNumber = 3265 |
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| DrugBank_Ref = {{drugbankcite|correct|drugbank}} |
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| KEGG = C00233 |
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| DrugBank = DB03229 |
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| KEGG_Ref = {{keggcite|correct|kegg}} |
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| KEGG = C00233 |
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| MeSHName = Alpha-ketoisocaproic+acid |
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| KEGG_Ref = {{keggcite|correct|kegg}} |
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| ChEBI = 48430 |
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| MeSHName = Alpha-ketoisocaproic+acid |
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| ChEMBL = 445647 |
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| ChEMBL_Ref = {{ebicite|correct|EBI}} |
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| ChEBI_Ref = {{ebicite|correct|EBI}} |
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| Beilstein = 1701823 |
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| ChEBI = 48430 |
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| 3DMet = B00066 |
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| ChEMBL = 445647 |
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| ChEMBL_Ref = {{ebicite|correct|EBI}} |
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| SMILES = CC(C)CC(=O)C(O)=O |
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| Beilstein = 1701823 |
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| SMILES1 = O=C(C(=O)O)CC(C)C |
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| 3DMet = B00066 |
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| StdInChI = 1S/C6H10O3/c1-4(2)3-5(7)6(8)9/h4H,3H2,1-2H3,(H,8,9) |
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| SMILES = CC(C)CC(=O)C(O)=O |
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| StdInChI_Ref = {{stdinchicite|correct|chemspider}} |
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| SMILES1 = O=C(C(=O)O)CC(C)C |
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| InChI = 1/C6H10O3/c1-4(2)3-5(7)6(8)9/h4H,3H2,1-2H3,(H,8,9) |
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| StdInChI = 1S/C6H10O3/c1-4(2)3-5(7)6(8)9/h4H,3H2,1-2H3,(H,8,9) |
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| StdInChIKey = BKAJNAXTPSGJCU-UHFFFAOYSA-N |
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| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}} |
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| StdInChI_Ref = {{stdinchicite|correct|chemspider}} |
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| InChI = 1/C6H10O3/c1-4(2)3-5(7)6(8)9/h4H,3H2,1-2H3,(H,8,9) |
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| InChIKey = BKAJNAXTPSGJCU-UHFFFAOYAG |
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| StdInChIKey = BKAJNAXTPSGJCU-UHFFFAOYSA-N |
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| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}} |
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| InChIKey = BKAJNAXTPSGJCU-UHFFFAOYAG |
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}} |
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}} |
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| Section2 = {{Chembox Properties |
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|Section2={{Chembox Properties |
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| C = 6 |
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| C = 6 |
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| H = 10 |
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| H = 10 |
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| O = 3 |
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| O = 3 |
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| ExactMass = 130.062994186 g mol<sup>-1</sup> |
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| Density = 1.055 g cm<sup>−3</sup> (at 20 °C) |
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| MeltingPtC = 8 to 10 |
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| Density = 1.055 g cm<sup>-3</sup> (at 20 °C) |
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| MeltingPtCL = 8 |
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| BoilingPtC = 85 |
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| BoilingPt_notes = at 13 mmHg |
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| MeltingPtCH = 10 |
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| BoilingPtC = 85 |
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| LogP = 0.133 |
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| pKa = 2.651 |
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| Boiling_notes = at 13 mmHg |
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| LogP = 0.133 |
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| pKb = 11.346 |
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| pKa = 2.651 |
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| pKb = 11.346 |
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}} |
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| Section3 = {{Chembox Hazards |
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|Section3={{Chembox Hazards |
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| EUClass = {{Hazchem C}} |
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| GHSPictograms = {{GHS05}} |
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| GHSSignalWord = Danger |
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| RPhrases = {{R34}} |
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| HPhrases = {{H-phrases|314}} |
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| SPhrases = {{S26}}, {{S36/37/39}}, {{S45}} |
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| PPhrases = {{P-phrases|260|264|280|301+330+331|303+361+353|304+340|305+351+338|310|321|363|405|501}} |
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'''α-Ketoisocaproic acid''' ('''α-KIC'''), also known as '''4-methyl-2-oxovaleric acid''', and its ] and ], '''α-ketoisocaproate''', are ]s in the ].<ref name="Wilson1" /> ] is an ], and its degradation is critical for many biological duties.<ref>{{Cite web|url=https://pubchem.ncbi.nlm.nih.gov/compound/Leucine|title = Leucine}}</ref> α-KIC is produced in one of the first steps of the pathway by ] by transferring the ] on L-leucine onto ], and replacing that amine with a ]. The degradation of L-leucine in the ] to this compound allows for the production of the ]s ] and ] as well. In the ], α-KIC can be converted to a vast number of compounds depending on the ]s and ] present, including ], ], ], and other biological molecules. Isovaleryl-CoA is the main compound synthesized from ɑ-KIC.<ref name="Wilson1">{{cite journal |last1=Wilson |first1=Jacob M. |last2=Fitschen |first2=Peter J. |last3=Campbell |first3=Bill |last4=Wilson |first4=Gabriel J. |last5=Zanchi |first5=Nelo |last6=Taylor |first6=Lem |last7=Wilborn |first7=Colin |last8=Kalman |first8=Douglas S. |last9=Stout |first9=Jeffrey R. |last10=Hoffman |first10=Jay R. |last11=Ziegenfuss |first11=Tim N. |last12=Lopez |first12=Hector L. |last13=Kreider |first13=Richard B. |last14=Smith-Ryan |first14=Abbie E. |last15=Antonio |first15=Jose |title=International Society of Sports Nutrition Position Stand: beta-hydroxy-beta-methylbutyrate (HMB) |journal=Journal of the International Society of Sports Nutrition |date=2 February 2013 |volume=10 |issue=1 |pages=6 |doi=10.1186/1550-2783-10-6 |doi-access=free |pmid=23374455 |pmc=3568064 }}</ref><ref name="Zanchi1">{{cite journal |last1=Zanchi |first1=Nelo Eidy |last2=Gerlinger-Romero |first2=Frederico |last3=Guimarães-Ferreira |first3=Lucas |last4=de Siqueira Filho |first4=Mário Alves |last5=Felitti |first5=Vitor |last6=Lira |first6=Fabio Santos |last7=Seelaender |first7=Marília |last8=Lancha |first8=Antonio Herbert |title=HMB supplementation: clinical and athletic performance-related effects and mechanisms of action |journal=Amino Acids |date=April 2011 |volume=40 |issue=4 |pages=1015–1025 |doi=10.1007/s00726-010-0678-0 |pmid=20607321 |s2cid=11120110 |url=https://repositorio.unal.edu.co/handle/unal/77957 }}</ref><ref name="Kohlmeier1">{{cite book |last1=Kohlmeier |first1=M |date=May 2015 |chapter=Leucine |title=Nutrient Metabolism: Structures, Functions, and Genes |edition=2nd |publisher=Academic Press |pages=385–388 |isbn=978-0-12-387784-0 }}</ref> α-KIC is a key ] present in the ] of people with ], along with other ]s.<ref name=NBK1319>{{cite book |first1=Kevin A |last1=Strauss |first2=Erik G |last2=Puffenberger |first3=Vincent J |last3=Carson |chapter=Maple Syrup Urine Disease |title=GeneReviews |year=1993 |publisher=University of Washington, Seattle |chapter-url=https://www.ncbi.nlm.nih.gov/books/NBK1319/ }}</ref> Derivatives of α-KIC have been studied in humans for their ability to improve physical performance during ] as a supplemental bridge between short-term and long-term exercise supplements. These studies show that α-KIC does not achieve this goal without other ] supplements present as well.<ref name="Stevens1">{{cite book |doi=10.1016/B978-0-12-396454-0.00044-8 |chapter=An Overview of Glycine-Arginine-Alpha-Ketoisocaproic Acid (GAKIC) in Sports Nutrition |title=Nutrition and Enhanced Sports Performance |year=2013 |last1=Stevens |first1=Bruce R. |pages=433–438 |isbn=978-0-12-396454-0 }}</ref> α-KIC has also been observed to reduce ] damage after eccentrically biased ]s in people who do not usually perform those exercises.<ref name="Van1">{{cite journal |last1=Someren |first1=Ken A. van |last2=Edwards |first2=Adam J. |last3=Howatson |first3=Glyn |title=Supplementation with β-Hydroxy- β-Methylbutyrate (HMB) and α-Ketoisocaproic Acid (KIC) Reduces Signs and Symptoms of Exercise-Induced Muscle Damage in Man |journal=International Journal of Sport Nutrition and Exercise Metabolism |date=1 August 2005 |volume=15 |issue=4 |pages=413–424 |doi=10.1123/ijsnem.15.4.413 |pmid=16286672 }}</ref> |
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==Biological activity== |
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===Supplements=== |
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α-KIC has been studied as a ] to aid in the performance of strenuous physical activity. Studies have shown that taking ɑ-KIC and its derivatives before acute physical activity led to an increase in muscle work by 10%, as well as a decrease in muscle ] during the early phase of the physical activity.<ref name="Stevens1"/> When taken with other supplements over a two-week period, such as ] (HMB), participants reported delayed onset of ], as well as other positive effects such as increased muscle girth.<ref name="Van1"/> It is important to note that studies have also suggested that ɑ-KIC taken alone did not have any significant positive impacts on physical performance, so it should be taken in conjunction with other ergogenic substances.<ref>{{cite journal |last1=Yarrow |first1=Joshua F |last2=Parr |first2=Jeffrey J |last3=White |first3=Lesley J |last4=Borsa |first4=Paul A |last5=Stevens |first5=Bruce R |title=The effects of short-term alpha-ketoisocaproic acid supplementation on exercise performance: a randomized controlled trial |journal=Journal of the International Society of Sports Nutrition |date=December 2007 |volume=4 |issue=1 |pages=2 |doi=10.1186/1550-2783-4-2 |doi-access=free |pmid=17908285 |pmc=2042499 }}</ref> ɑ-KIC is not available as a supplement on its own, but its decarboxylated form HMB is available in calcium salt capsules or powder.<ref name="Wilson1"/> |
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===Applications=== |
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The biochemical implications of α-KIC are largely connected to other ]. ], skeletal muscle ], and skeletal muscle ] have all been noted to change when ɑ-KIC is taken. There is not much research into the specific mechanisms taking part in these processes, but there is a noticeable correlation between ɑ-KIC ingestion and increased skeletal muscle protein synthesis, regeneration, and proteolysis.<ref name="Wilson1"/> |
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==Toxicity== |
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Multiple studies have demonstrated that there have been no adverse effects on humans nor animals that ingested α-KIC or HMB.<ref>{{cite journal |last1=Nissen |first1=S. |last2=Sharp |first2=R. L. |last3=Panton |first3=L. |last4=Vukovich |first4=M. |last5=Trappe |first5=S. |last6=Fuller |first6=J. C. |title=β-Hydroxy-β-Methylbutyrate (HMB) Supplementation in Humans Is Safe and May Decrease Cardiovascular Risk Factors |journal=The Journal of Nutrition |date=1 August 2000 |volume=130 |issue=8 |pages=1937–1945 |doi=10.1093/jn/130.8.1937 |pmid=10917905 |doi-access=free }}</ref><ref>{{cite journal |last1=Baxter |first1=J.H. |last2=Carlos |first2=J.L. |last3=Thurmond |first3=J. |last4=Rehani |first4=R.N. |last5=Bultman |first5=J. |last6=Frost |first6=D. |title=Dietary toxicity of calcium β-hydroxy-β-methyl butyrate (CaHMB) |journal=Food and Chemical Toxicology |date=December 2005 |volume=43 |issue=12 |pages=1731–1741 |doi=10.1016/j.fct.2005.05.016 |pmid=16006030 }}</ref> |
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In patients with ], who are unable to metabolize the branched chain alpha keto acids, α-KIC is believed to be one of the key mediators of neurotoxicity.<ref>{{Cite journal|url=https://link.springer.com/article/10.1007/s10545-011-9333-5|doi = 10.1007/s10545-011-9333-5|title = Interrupting the mechanisms of brain injury in a model of maple syrup urine disease encephalopathy|year = 2012|last1 = Zinnanti|first1 = William J.|last2 = Lazovic|first2 = Jelena|journal = Journal of Inherited Metabolic Disease|volume = 35|issue = 1|pages = 71–79|pmid = 21541722|s2cid = 1253267}}</ref> |
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==Medical use== |
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Branched-chain alpha-keto acids such as α-KIC are found in high concentrations in the urine of people who suffer from Maple Syrup Urine Disease. This is disease is caused by a partial ] deficiency, which leads to a buildup of branched-chain alpha-keto acids, including α-KIC and HMB.<ref name="Strauss1">{{cite journal |last1=Strauss |first1=Kevin A. |last2=Wardley |first2=Bridget |last3=Robinson |first3=Donna |last4=Hendrickson |first4=Christine |last5=Rider |first5=Nicholas L. |last6=Puffenberger |first6=Erik G. |last7=Shelmer |first7=Diana |last8=Moser |first8=Ann B. |last9=Morton |first9=D. Holmes |title=Classical maple syrup urine disease and brain development: Principles of management and formula design |journal=Molecular Genetics and Metabolism |date=April 2010 |volume=99 |issue=4 |pages=333–345 |doi=10.1016/j.ymgme.2009.12.007 |pmid=20061171 |pmc=3671925 }}</ref> These keto-acids build up in the ],<ref name="Wilson1"/><ref name="Zanchi1"/><ref name="Kohlmeier1"/> and since limited isovaleryl-CoA can be produced, these keto-acids must be ]d in the urine as α-KIC, HMB, and many other similar ]s. Flare-ups in people who have this condition are caused due to poor diet.<ref name=NBK1319/> Symptoms of Maple Syrup Urine Disease include sweet smelling urine, ], ], and in serious cases ] of the brain, ], ], or ].<ref name="Strauss1"/><ref name=NBK1319/> Treatment includes lowering leucine intake and a specialized diet to make up for the lack of leucine ingestion.<ref name=NBK1319/> |
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==Leucine metabolism== |
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{{Leucine metabolism in humans|align=center}} |
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{{clear}} |
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== References == |
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{{reflist}} |
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{{Amino acid metabolism intermediates}} |
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{{DEFAULTSORT:Ketoisocaproic acid, alpha-}} |
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] |