베타-하이드록시 베타-메틸글루타릴-CoA 문서 원본 보기

{{Chembox
| verifiedrevid = 450656813
| ImageFile=HMG coenzyme A.svg
| ImageSize=300px
| IUPACName=(9R,21S)-1-[(2R,3S,4R,5R)-5-(6-amino-9H-purin-9-yl)-4-hydroxy-3-(phosphonooxy)tetrahydrofuran-2-yl]-3,5,9,21-tetrahydroxy-8,8,21-trimethyl-10,14,19-trioxo-2,4,6-trioxa-18-thia-11,15-diaza-3,5-diphosphatricosan-23-oic acid 3,5-dioxide
| OtherNames=
|Section1={{Chembox Identifiers
| IUPHAR_ligand = 3040
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID = 392859
| InChI = 1/C27H44N7O20P3S/c1-26(2,21(40)24(41)30-5-4-15(35)29-6-7-58-17(38)9-27(3,42)8-16(36)37)11-51-57(48,49)54-56(46,47)50-10-14-20(53-55(43,44)45)19(39)25(52-14)34-13-33-18-22(28)31-12-32-23(18)34/h12-14,19-21,25,39-40,42H,4-11H2,1-3H3,(H,29,35)(H,30,41)(H,36,37)(H,46,47)(H,48,49)(H2,28,31,32)(H2,43,44,45)/t14-,19-,20-,21+,25-,27+/m1/s1
| InChIKey = CABVTRNMFUVUDM-VRHQGPGLBX
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| StdInChI = 1S/C27H44N7O20P3S/c1-26(2,21(40)24(41)30-5-4-15(35)29-6-7-58-17(38)9-27(3,42)8-16(36)37)11-51-57(48,49)54-56(46,47)50-10-14-20(53-55(43,44)45)19(39)25(52-14)34-13-33-18-22(28)31-12-32-23(18)34/h12-14,19-21,25,39-40,42H,4-11H2,1-3H3,(H,29,35)(H,30,41)(H,36,37)(H,46,47)(H,48,49)(H2,28,31,32)(H2,43,44,45)/t14-,19-,20-,21+,25-,27+/m1/s1
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
| StdInChIKey = CABVTRNMFUVUDM-VRHQGPGLSA-N
| CASNo_Ref = {{cascite|correct|??}}
| CASNo=1553-55-5
| PubChem = 445127
| ChEBI_Ref = {{ebicite|correct|EBI}}
| ChEBI = 61659
| SMILES = O=C(O)C[C@@](O)(C)CC(=O)SCCNC(=O)CCNC(=O)[C@H](O)C(C)(C)COP(=O)(O)OP(=O)(O)OC[C@H]3O[C@@H](n2cnc1c(ncnc12)N)[C@H](O)[C@@H]3OP(=O)(O)O
| MeSHName=HMG-CoA
  }}
|Section2={{Chembox Properties
| Formula=C<sub>27</sub>H<sub>44</sub>N<sub>7</sub>O<sub>20</sub>P<sub>3</sub>S
| MolarMass=911.661 g/mol
| Appearance=
| Density=
| MeltingPt=
| BoilingPt=
| Solubility=
  }}
|Section3={{Chembox Hazards
| MainHazards=
| FlashPt=
| AutoignitionPt =
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'''β-하이드록시 β-메틸글루타릴-CoA'''({{llang|en|β-hydroxy β-methylglutaryl-CoA}}, '''HMG-CoA''') 또는 '''3-하이드록시 3-메틸글루타릴-CoA'''({{llang|en|3-hydroxy 3-methylglutaryl-CoA}})는 [[메발론산 경로]] 및 [[케톤체생성]] 경로의 [[대사 중간생성물]]이다. β-하이드록시 β-메틸글루타릴-CoA(HMG-CoA)는 [[β-하이드록시 β-메틸글루타릴-CoA 생성효소]](HMG-CoA 생성효소)에 의해 [[아세틸-CoA]]와 [[아세토아세틸-CoA]]로부터 생성된다. 1950년대에 [[일리노이 대학교 어배너-섐페인]]의 마이너 제서 쿤(Minor Jesser Coon)과 비말 쿠마르 바크하와트(Bimal Kumar Bachhawat)의 연구가 이러한 발견을 이끌었다.<ref name="Classics in Indian Medicine">{{저널 인용| url=http://www.nmji.in/archives/Volume-28/Issue-3/Classics-in-Indian-Medicine.pdf | title=Classics in Indian Medicine | first = Debi P. | last = Sarkar | name-list-format = vanc | journal=The National Medical Journal of India | year=2015 | issue=28 | pages=3 | url-status=dead | archive-url=https://web.archive.org/web/20160531082638/http://www.nmji.in/archives/Volume-28/Issue-3/Classics-in-Indian-Medicine.pdf | archive-date=2016-05-31 | df= }}</ref><ref name="An outstanding scientist and a splendid human being">{{저널 인용| url=https://glycob.oxfordjournals.org/content/7/4/453.1.full.pdf | title=An outstanding scientist and a splendid human being | first = Avadhesha | last = Surolia | name-list-format = vanc | journal=Glycobiology | year=1997 | volume=7 | issue=4 | pages=v–ix | doi = 10.1093/glycob/7.4.453}}</ref>

β-하이드록시 β-메틸글루타릴-CoA(HMG-CoA)는 [[류신]], [[아이소류신]], [[발린]]과 같은 [[가지사슬 아미노산]]의 [[물질대사|대사]] 과정에서의 [[대사 중간생성물]]이다.<ref name="HMG biosynthesis">{{웹 인용|title=Valine, leucine and isoleucine degradation - Reference pathway|url=http://www.genome.jp/kegg-bin/show_pathway?map00280+C00356|website=Kyoto Encyclopedia of Genes and Genomes|publisher=Kanehisa Laboratories|date=27 January 2016|access-date=1 February 2018}}</ref> β-메틸글루타코닐-CoA(MG-CoA)와 β-하이드록시 β-메틸뷰티릴-CoA(HMB-CoA)는 β-하이드록시 β-메틸글루타릴-CoA(HMG-CoA)의 직접적인 전구물질들이다.

== 생합성 ==
{|
|[[파일:HMB biosynthesis and metabolism.png|섬네일|600px|왼쪽|사람에서 [[류신|L-류신]]과 관련한 [[β-하이드록시 β-메틸뷰티르산]](HMB) 및 [[아이소발레릴-CoA]]에 대한 [[대사 경로]]. 두 가지 주요 경로 중 L-류신은 대부분 아이소발레릴-CoA로 대사되는 반면, β-하이드록시 β-메틸뷰티르산(HMB)으로 대사되는 경우는 약 5%에 불과하다.<ref>{{저널 인용| vauthors = Wilson JM, Fitschen PJ, Campbell B, Wilson GJ, Zanchi N, Taylor L, Wilborn C, Kalman DS, Stout JR, Hoffman JR, Ziegenfuss TN, Lopez HL, Kreider RB, Smith-Ryan AE, Antonio J | title = International Society of Sports Nutrition Position Stand: beta-hydroxy-beta-methylbutyrate (HMB) | journal = Journal of the International Society of Sports Nutrition | volume = 10 | issue = 1 | pages = 6 | date = February 2013 | pmid = 23374455 | pmc = 3568064 | doi = 10.1186/1550-2783-10-6}}</ref><ref>{{저널 인용| vauthors = Zanchi NE, Gerlinger-Romero F, Guimarães-Ferreira L, de Siqueira Filho MA, Felitti V, Lira FS, Seelaender M, Lancha AH | title = HMB supplementation: clinical and athletic performance-related effects and mechanisms of action | journal = Amino Acids | volume = 40 | issue = 4 | pages = 1015–1025 | date = April 2011 | pmid = 20607321 | doi = 10.1007/s00726-010-0678-0 | quote = HMB is a metabolite of the amino acid leucine (Van Koverin and Nissen 1992), an essential amino acid. The first step in HMB metabolism is the reversible transamination of leucine to [α-KIC] that occurs mainly extrahepatically (Block and Buse 1990). Following this enzymatic reaction, [α-KIC] may follow one of two pathways. In the first, HMB is produced from [α-KIC] by the cytosolic enzyme KIC dioxygenase (Sabourin and Bieber 1983). The cytosolic dioxygenase has been characterized extensively and differs from the mitochondrial form in that the dioxygenase enzyme is a cytosolic enzyme, whereas the dehydrogenase enzyme is found exclusively in the mitochondrion (Sabourin and Bieber 1981, 1983). Importantly, this route of HMB formation is direct and completely dependent of liver KIC dioxygenase. Following this pathway, HMB in the cytosol is first converted to cytosolic β-hydroxy-β-methylglutaryl-CoA (HMG-CoA), which can then be directed for cholesterol synthesis (Rudney 1957) (Fig. 1). In fact, numerous biochemical studies have shown that HMB is a precursor of cholesterol (Zabin and Bloch 1951; Nissen et al. 2000).<!--<br /><br /> In the second pathway, after transamination, [α-KIC] in liver generates isovaleryl-CoA through the enzymatic action of branched-chain ketoacid dehydrogenase (BCKD) and after several steps, there is production of HMG-CoA through the enzyme HMG-CoA synthase (Fig. 1). Under normal conditions the majority of KIC is converted into isovaleryl-CoA, in which approximately 5% of leucine is metabolized into HMB (Wilson et al. 2008; Van Koverin and Nissen 1992). However, Nissen and Abumrad (1997) provided evidence that the primary fate of HMB is probably conversion to HMG-CoA in the liver, for cholesterol biosynthesis.--> }}</ref><ref>{{서적 인용| vauthors=Kohlmeier M | title=Nutrient Metabolism: Structures, Functions, and Genes | date=May 2015 | publisher=Academic Press | isbn=978-0-12-387784-0 | pages=385–388 | edition=2nd | section-url=https://books.google.com/books?id=aTQTAAAAQBAJ&pg=PA387&q=beta-hydroxy%20beta-methylbutyrate%20HMB#v=onepage | url=https://books.google.com/books?id=aTQTAAAAQBAJ&printsec=frontcover#v=onepage | accessdate=6 June 2016 | section=Leucine | quote= Energy fuel: Eventually, most Leu is broken down, providing about 6.0kcal/g. About 60% of ingested Leu is oxidized within a few hours&nbsp;... Ketogenesis: A significant proportion (40% of an ingested dose) is converted into acetyl-CoA and thereby contributes to the synthesis of ketones, steroids, fatty acids, and other compounds}}<br />[https://books.google.com/books?id=aTQTAAAAQBAJ&pg=PA386#v=onepage&q&f=false Figure 8.57: Metabolism of {{smallcaps all|L}}-leucine]</ref>]]
|}

== 메발론산 경로 ==
{{본문|메발론산 경로}}
[[메발론산]]의 합성은 두 분자의 [[아세틸-CoA]]가 [[싸이올레이스]]에 의해 [[클라이젠 축합]]되어 [[아세토아세틸-CoA]]를 생성하는 것으로 시작된다. 다음 반응은 아세틸-CoA와 아세토아세틸-CoA가 β-하이드록시 β-메틸글루타릴-CoA 생성효소(HMG-CoA 생성효소)에 의해 β-하이드록시 β-메틸글루타릴-CoA(HMG-CoA)를 생성하는 반응이다.<ref>{{서적 인용|title=Biochemistry|url=https://archive.org/details/biochemistrybioc0000garr|last=Garrett|first=Reginald H. | name-list-format = vanc |publisher=Cengage Learning|year=2013|isbn=978-1-305-57720-6|location=|pages=856}}</ref>

메발론산 생합성의 마지막 단계는 β-하이드록시 β-메틸글루타릴-CoA(HMG-CoA)가 [[NADPH]] 의존성 [[산화환원효소]]인 [[β-하이드록시 β-메틸글루타릴-CoA 환원효소]](HMG-CoA 환원효소)에 의해 메발론산으로 전환되는 것이며, 이 단계는 메발론산 경로의 주요 조절 지점이다. [[메발론산]]은 사람에서 [[콜레스테롤]]을 포함한 다양한 최종 산물들을 포괄하는 [[아이소프레노이드]]들의 [[전구물질]]로 역할을 한다.<ref>{{저널 인용| vauthors = Haines BE, Steussy CN, Stauffacher CV, Wiest O | title = Molecular modeling of the reaction pathway and hydride transfer reactions of HMG-CoA reductase | journal = Biochemistry | volume = 51 | issue = 40 | pages = 7983–95 | date = October 2012 | pmid = 22971202 | pmc = 3522576 | doi = 10.1021/bi3008593 | url = http://pubs.acs.org/doi/10.1021/bi3008593 }}</ref>
{|
|[[파일:Mevalonate pathway.svg|500px|섬네일|왼쪽|메발론산 경로]]
|}

== 케톤체생성 경로 ==
[[β-하이드록시 β-메틸글루타릴-CoA 분해효소]](HMG-CoA 분해효소)는 β-하이드록시 β-메틸글루타릴-CoA(HMG-CoA)를 [[아세틸-CoA]]와 [[아세토아세트산]]으로 분해한다.
{|
|[[파일:Ketogenesis.svg|500px|섬네일|왼쪽|케톤체생성 경로]]
|}

== 같이 보기 ==
* [[베타-메틸글루타코닐-CoA|β-메틸글루타코닐-CoA]]
* [[스테로이드생성 효소]]

== 각주 ==
{{각주}}

{{스테로이드 대사 중간생성물들}}
{{아미노산 대사 중간생성물들}}
{{위키데이터 속성 추적}}

[[분류:조효소 A의 싸이오에스터]]