methylmalonyl-CoA mutase

同

isomerase

WordNet

1. an enzyme that catalyzes its substrate to an isomeric form
2. the 3rd letter of the Roman alphabet (同)c
3. (music) the keynote of the scale of C major
4. a general-purpose programing language closely associated with the UNIX operating system

PrepTutorEJDIC

1. carbonの化学記号
2. cobaltの化学記号

Wikipedia preview

出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2012/09/12 09:54:58」(JST)

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Methylmalonyl CoA mutase
Rendering based on PDB 2XIJ.
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 2XIJ, 2XIQ, 3BIC
Identifiers
Symbols	MUT; MCM
External IDs	OMIM: 609058 MGI: 97239 HomoloGene: 20097 GeneCards: MUT Gene
EC number	5.4.99.2
Gene Ontology Molecular function • methylmalonyl-CoA mutase activity • cobalamin binding • metal ion binding • modified amino acid binding Cellular component • mitochondrion • mitochondrial matrix Biological process • fatty acid beta-oxidation • post-embryonic development • short-chain fatty acid catabolic process • cellular lipid metabolic process • small molecule metabolic process • homocysteine metabolic process Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	4594	17850
Ensembl	ENSG00000146085	ENSMUSG00000023921
UniProt	P22033	P16332
RefSeq (mRNA)	NM_000255.3	NM_008650.3
RefSeq (protein)	NP_000246.2	NP_032676.2
Location (UCSC)	Chr 6: 49.4 – 49.43 Mb	Chr 17: 40.93 – 40.96 Mb
PubMed search	[1]	[2]

methylmalonyl-CoA mutase
Identifiers
EC number	5.4.99.2
CAS number	9023-90-9
Databases
IntEnz	IntEnz view
BRENDA	BRENDA entry
ExPASy	NiceZyme view
KEGG	KEGG entry
MetaCyc	metabolic pathway
PRIAM	profile
PDB structures	RCSB PDB PDBe PDBsum
Gene Ontology	AmiGO / EGO
Search PMC articles PubMed articles

Methylmalonyl Coenzyme A mutase, also known as MCM is an enzyme that catalyzes the isomerization of methylmalonyl-CoA to succinyl-CoA and it is involved in key metabolic pathways. It requires a vitamin B₁₂-derived prosthetic group, adenosylcobalamin, to function.

Function

The substrate of methylmalonyl-CoA mutase, methylmalonyl-CoA, is primarily derived from propionyl-CoA, a substance formed from the catabolism and digestion of isoleucine, valine, threonine, methionine, thymine, cholesterol, or odd-chain fatty acids.

The product of the enzyme, succinyl-CoA, is a key molecule of the TCA cycle.

MCM resides in the mitochondria, where a number of substances, including the branched-chain amino acids isoleucine and valine, as well as methionine, threonine, thymine and odd-chain fatty acids, are metabolized via methylmalonate semialdehyde (MMlSA) or propionyl-CoA (Pr-CoA) to a common compound - methylmalonyl-CoA (MMl-CoA).

Human Genetics

The gene encoding for this enzyme in humans is known as MUT.

Pathology

A deficiency of this enzyme is responsible for an inherited disorder of metabolism, Methylmalonyl-CoA mutase deficiency, which is one of the causes of methylmalonic acidemia.

Mechanism

MUT reaction mechanism begins with homolytic cleavage of AdoB12's C-Co(III) bond, the C and Co atoms each acquire one of the electrons that formed the cleaved electron pair bond. The Co ion, therefore, fluctuates between its Co(III) and Co(II) oxidation states [the two states are spectroscopically distinguishable: Co(III) is red and diamagnetic (no unpaired electrons), whereas Co(II) is yellow and paramagnetic (unpaired electrons)]. Hence, the role of coenzyme B-12 in the catalytic process is that of a reversible free radical generator. The C-Co(III) bond is well suited to this function because it is inherently weak (dissociation energy = 109 kJ/mol) and appears to be further weakened through steric interactions with the enzyme. A homolytic cleavage reaction is unusual in biology; most other biological bond cleavage reactions occur via heterolytic cleavage (in which the electron pair forming the cleaved bond is fully acquired by one of the separating atoms).

See also

• MMAA
• MMAB
• MMACHC
• MMADHC

References

Further reading

• Ledley FD, Rosenblatt DS (1997). "Mutations in mut methylmalonic acidemia: clinical and enzymatic correlations.". Hum. Mutat. 9 (1): 1–6. doi:10.1002/(SICI)1098-1004(1997)9:1<1::AID-HUMU1>3.0.CO;2-E. PMID 8990001. 
• Ludwig ML, Matthews RG (1997). "Structure-based perspectives on B12-dependent enzymes.". Annu. Rev. Biochem. 66: 269–313. doi:10.1146/annurev.biochem.66.1.269. PMID 9242908. 
• Lubrano R, Elli M, Rossi M, et al. (2007). "Renal transplant in methylmalonic acidemia: could it be the best option? Report on a case at 10 years and review of the literature.". Pediatr. Nephrol. 22 (8): 1209–14. doi:10.1007/s00467-007-0460-z. PMID 17401587. 
• Frenkel EP, Kitchens RL (1978). "Intracellular localization of hepatic propionyl-CoA carboxylase and methylmalonyl-CoA mutase in humans and normal and vitamin B12 deficient rats.". Br. J. Haematol. 31 (4): 501–13. doi:10.1111/j.1365-2141.1975.tb00885.x. PMID 24458. 
• Crane AM, Jansen R, Andrews ER, Ledley FD (1992). "Cloning and expression of a mutant methylmalonyl coenzyme A mutase with altered cobalamin affinity that causes mut- methylmalonic aciduria.". J. Clin. Invest. 89 (2): 385–91. doi:10.1172/JCI115597. PMC 442864. PMID 1346616. //www.ncbi.nlm.nih.gov/pmc/articles/PMC442864/. 
• Crane AM, Martin LS, Valle D, Ledley FD (1992). "Phenotype of disease in three patients with identical mutations in methylmalonyl CoA mutase.". Hum. Genet. 89 (3): 259–64. doi:10.1007/BF00220536. PMID 1351030. 
• Raff ML, Crane AM, Jansen R, et al. (1991). "Genetic characterization of a MUT locus mutation discriminating heterogeneity in mut0 and mut- methylmalonic aciduria by interallelic complementation.". J. Clin. Invest. 87 (1): 203–7. doi:10.1172/JCI114972. PMC 295026. PMID 1670635. //www.ncbi.nlm.nih.gov/pmc/articles/PMC295026/. 
• Jansen R, Ledley FD (1990). "Heterozygous mutations at the mut locus in fibroblasts with mut0 methylmalonic acidemia identified by polymerase-chain-reaction cDNA cloning.". Am. J. Hum. Genet. 47 (5): 808–14. PMC 1683687. PMID 1977311. //www.ncbi.nlm.nih.gov/pmc/articles/PMC1683687/. 
• Nham SU, Wilkemeyer MF, Ledley FD (1991). "Structure of the human methylmalonyl-CoA mutase (MUT) locus.". Genomics 8 (4): 710–6. doi:10.1016/0888-7543(90)90259-W. PMID 1980486. 
• Ledley FD, Lumetta M, Nguyen PN, et al. (1988). "Molecular cloning of L-methylmalonyl-CoA mutase: gene transfer and analysis of mut cell lines.". Proc. Natl. Acad. Sci. U.S.A. 85 (10): 3518–21. doi:10.1073/pnas.85.10.3518. PMC 280243. PMID 2453061. //www.ncbi.nlm.nih.gov/pmc/articles/PMC280243/. 
• Jansen R, Kalousek F, Fenton WA, et al. (1989). "Cloning of full-length methylmalonyl-CoA mutase from a cDNA library using the polymerase chain reaction.". Genomics 4 (2): 198–205. doi:10.1016/0888-7543(89)90300-5. PMID 2567699. 
• Fenton WA, Hack AM, Kraus JP, Rosenberg LE (1987). "Immunochemical studies of fibroblasts from patients with methylmalonyl-CoA mutase apoenzyme deficiency: detection of a mutation interfering with mitochondrial import.". Proc. Natl. Acad. Sci. U.S.A. 84 (5): 1421–4. doi:10.1073/pnas.84.5.1421. PMC 304442. PMID 2881300. //www.ncbi.nlm.nih.gov/pmc/articles/PMC304442/. 
• Zoghbi HY, O'Brien WE, Ledley FD (1989). "Linkage relationships of the human methylmalonyl CoA mutase to the HLA and D6S4 loci on chromosome 6.". Genomics 3 (4): 396–8. doi:10.1016/0888-7543(88)90135-8. PMID 2907507. 
• Kolhouse JF, Utley C, Allen RH (1980). "Isolation and characterization of methylmalonyl-CoA mutase from human placenta.". J. Biol. Chem. 255 (7): 2708–12. PMID 6102092. 
• Fenton WA, Hack AM, Willard HF, et al. (1982). "Purification and properties of methylmalonyl coenzyme A mutase from human liver.". Arch. Biochem. Biophys. 214 (2): 815–23. doi:10.1016/0003-9861(82)90088-1. PMID 6124211. 
• Qureshi AA, Crane AM, Matiaszuk NV, et al. (1994). "Cloning and expression of mutations demonstrating intragenic complementation in mut0 methylmalonic aciduria.". J. Clin. Invest. 93 (4): 1812–9. doi:10.1172/JCI117166. PMC 294249. PMID 7909321. //www.ncbi.nlm.nih.gov/pmc/articles/PMC294249/. 
• Crane AM, Ledley FD (1994). "Clustering of mutations in methylmalonyl CoA mutase associated with mut- methylmalonic acidemia.". Am. J. Hum. Genet. 55 (1): 42–50. PMC 1918235. PMID 7912889. //www.ncbi.nlm.nih.gov/pmc/articles/PMC1918235/. 
• Janata J, Kogekar N, Fenton WA (1998). "Expression and kinetic characterization of methylmalonyl-CoA mutase from patients with the mut- phenotype: evidence for naturally occurring interallelic complementation.". Hum. Mol. Genet. 6 (9): 1457–64. doi:10.1093/hmg/6.9.1457. PMID 9285782. 

External links

• GeneReviews/NIH/NCBI/UW entry on Methylmalonic Acidemia
• Methylmalonyl-CoA+Mutase at the US National Library of Medicine Medical Subject Headings (MeSH)

UpToDate Contents

全文を閲覧するには購読必要です。 To read the full text you will need to subscribe.

• 1. 有機酸血症 organic acidemias
• 2. 小児における非典型的溶血性尿毒症症候群 atypical hemolytic uremic syndrome in children
• 3. ビタミンB12および葉酸塩欠乏症の病因および臨床症状 etiology and clinical manifestations of vitamin b12 and folate deficiency
• 4. ホスホグリセリン酸キナーゼ欠損症およびホスホグリセリン酸ムターゼ欠損症 phosphoglycerate kinase deficiency and phosphoglycerate mutase deficiency
• 5. ビタミンB12および葉酸塩欠乏症の生理学 physiology of vitamin b12 and folate deficiency

English Journal

• A Primary Study on Down-Regulated miR-9-1 and Its Biological Significances in Methylmalonic Acidemia.

• Li Y1, Peng T, Wang X, Duan R, Gao H, Guan W, Teng J, Jia Y.
• Journal of molecular neuroscience : MN.J Mol Neurosci.2014 Jun;53(2):280-6. doi: 10.1007/s12031-013-0218-y. Epub 2014 Jan 4.
• Methylmalonic acidemia (MMA) is a metabolic disorder, which is caused by a deficiency of the mitochondrial enzyme methylmalonyl-CoA mutase. MMA diagnosis is dependent on the method of gas chromatography-mass spectrometry, which is expensive, complicated, and time consuming. Currently, microRNAs (miR
• PMID 24390963

• Methylmalonic acidemia: A megamitochondrial disorder affecting the kidney.

• Zsengellér ZK1, Aljinovic N, Teot LA, Korson M, Rodig N, Sloan JL, Venditti CP, Berry GT, Rosen S.
• Pediatric nephrology (Berlin, Germany).Pediatr Nephrol.2014 May 28. [Epub ahead of print]
• BACKGROUND: Classical (or isolated) methylmalonic acidemia (MMA) is a heterogeneous inborn error of metabolism most typically caused by mutations in the vitamin B12-dependent enzyme methylmalonyl-CoA mutase (MUT). With the improved survival of individuals with MMA, chronic kidney disease has become
• PMID 24865477

• Renal involvement in a patient with cobalamin A type (cblA) methylmalonic aciduria: a 42-year follow-up.

• Haarmann A1, Mayr M, Kölker S, Baumgartner ER, Schnierda J, Hopfer H, Devuyst O, Baumgartner MR.
• Molecular genetics and metabolism.Mol Genet Metab.2013 Dec;110(4):472-6. doi: 10.1016/j.ymgme.2013.08.021. Epub 2013 Sep 17.
• Chronic renal failure is a well-known long-term complication of methylmalonic aciduria (MMA-uria), occurring even under apparently optimal metabolic management. The onset of renal dysfunction seems to be dependent on the type of defect and vitamin B12-responsiveness. We report on a patient with a vi
• PMID 24095221

Japanese Journal

• ビタミンB_<12>欠乏ラットの脳におけるOtx2遺伝子発現量の変動

• 勝島 啓佑,上川 篤志,河田 哲典 [他],前川 昭男,小林 謙一,田所 忠弘,山本 祐司
• ビタミン 82(11), 595-599, 2008-11-25
• … (B_<12>) is a coenzyme of methionine synthase (MS) and methylmalonyl-CoA mutase. …
• NAID 110006990489

• ビタミンB_<12>と精子形成(<特集>「ビタミン・ミネラルと生殖」[I])

• 山田 和弘,河田 哲典,前川 昭男
• ビタミン 82(1), 11-17, 2008-01-25
• … is a cofactor for two enzymes, i.e. methionine synthase and methylmalonyl-CoA mutase. … According to earlier studies, methionine synthase, rather than methylmalonyl-CoA mutase, may be responsible for the testicular injury when animals are in B_<12>-deficiency. …
• NAID 110006571393

• Occurrence of 5'-Deoxyadenosylcobalamin and Its Physiological Function as the Coenzyme of Methylmalonyl-CoA Mutase in a Marine Eukaryotic Microorganism, Schizochytrium limacinum SR21

• , , [他], , ,
• Journal of nutritional science and vitaminology 53(6), 471-475, 2007-12
• … A considerably high activity (about 38mU/mg protein) of 5'-deoxyadenosylcobalamin-dependent methylmalonyl-CoA mutase (EC 5.4.99.2) involved in amino acid and odd-chain fatty acid metabolism was found in the cell homogenate of S. …
• NAID 110006531865

Related Links

• Methylmalonyl-CoA mutase deficiencyとは - goo Wikipedia ...

Methylmalonyl-CoA mutase deficiency From Wikipedia, the free encyclopedia Jump to: navigation, search Methylmalonyl-CoA mutase deficiency Classification and external resources OMIM 251000 DiseasesDB 29509 Methylmalonyl ...

• methylmalonyl-CoA mutase - definition of methylmalonyl-CoA ...

Samples obtained from the original NBS specimens of confirmed cases with [beta]-cystathionine synthase deficiency (n = 4), propionyl-CoA carboxylase deficiency (n = 2), methylmalonyl-CoA mutase deficiency (n = 4), Cbl C ...

Related Pictures

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★リンクテーブル★

リンク元	「ビタミンB12」「プロピオン酸」「プロピオニルCoA」「メチルマロニルCoAムターゼ」
関連記事	「C」「CoA」「mutase」「COA」「Co」

「ビタミンB12」

　　[★]

英

vitamin B12

同

コバラミン cobalamin

商

アリチア配合

関

シアノコバラミン、悪性貧血、ビタミン、メチルコバラミン

• 構造：FB.387

吸収

• 食物(コバラミン＋蛋白質)→胃(コバラミン)＋壁細胞が分泌する糖タンパク;内因子→コバラミン-内因子複合体→回腸 (SP.742)

回腸上皮細胞の刷子縁膜にコバラミン-内因子複合体に特異的なレセプターが存在 (SP.742)

細胞内ではβグロブリン(トランスコバラミン II)と結合して血中に入り組織に運ばれる (SPC.280, SPC.742)

部位：　ビタミンB12は回腸。　葉酸は空腸。　鉄も空腸、ついでに十二指腸でも。

機能

• コバラミン依存の酵素は全部で十数種ある。コバラミン依存の酵素は分子内転移、メチル転移を触媒 (FB.387)
• 正常ミエリンの維持 (SPC.280)
• 葉酸の代謝(葉酸は核酸代謝に関わっている) (SPC.280)
• 奇数脂肪酸の酸化 (FB.386)

メチルマロニルCoAムターゼの補酵素(奇数脂肪酸の酸化)

補酵素

• methylmalonyl-CoA mutase：
• methionine synthase：homocysteine + methyl THF－→methionine + THF

必要量

• 一日の消費量(排泄)：1-3ug (体の貯蔵量の-0.1%) (HIM.643)
• 体に貯蔵されてる量：2-3mg　→　摂取しなくとも3-4年は欠乏しない

基準値

• 260-1,050pg/ml(192-775pmol/ml)

判定

低値

• 巨赤芽球貧血

• 悪性貧血(内因子抗体、壁細胞抗体？)
• 胃切除後
• 萎縮性胃炎

• 吸収不良をきたす病態：クローン病、セリアック病、吸収不良症候群

高値

• 血液疾患：顆粒球増加を示す疾患　　　←　　顆粒球由来のビタミンB12輸送蛋白(トランスコバラミン?)が増加するため(QB.G-257)、崩壊した白血球から放出するため(YN.G-53)

• 慢性骨髄性白血病、真性多血症

臨床関連

• ビタミンB₁₂欠乏症
• 悪性貧血
• 慢性骨髄性白血病

• 白血球の破壊により末梢へのビタミンB12の漏出

• 亜急性連合性脊髄変性症 SCDC

• http://www.shc.usp.ac.jp/shibata/5-16-4.pdf

「プロピオン酸」

　　[★]

英

propionic acid

同

プロパン酸、プロパン

関

カルボン酸

• http://ja.wikipedia.org/wiki/%E3%83%97%E3%83%AD%E3%83%94%E3%82%AA%E3%83%B3%E9%85%B8
• C3H6O2
• CH3-CH2-COOH

• プロピオン酸（プロピオンさん、propionic acid）は示性式CH₃CH₂COOH、分子量74.08のカルボン酸。IUPAC命名法ではプロパン酸 (propanoic acid) となる。CAS登録番号は79-09-4。

物性

• 単体は融点−21℃、沸点141℃の無色の液体で、不快な臭気を有する。水、エタノール、クロロホルム、エーテルなどに溶けやすい。1-プロパノール、プロピオンアルデヒドの酸化によって得られる。

反芻動物におけるプロピオン酸

• 反芻胃で食物の中のセルロースやヘミセルロースを嫌気発酵して、プロピオン酸などの短鎖脂肪酸を生成している。

ヒト(非反芻動物を含む)におけるプロピオン酸

• 奇数脂肪酸のβ酸化、イソロイシンとコレステロール側鎖の酸化によって得られる。(HBC.169)

代謝

HBC. 169

• プロピオン酸　＋　CoA-SH　＋　ATP　－－(acyl-CoA synthetase + Mg2+)－→　AMP　＋　PPi　＋　プロピオニルCoA
• プロピオニルCoA　＋　CO2　＋　H2O　＋　ATP　－－(propionyl-CoA carboxylase+ビオチン)－→　D-メチルマロニルCoA　＋　ADP　＋　Pi

→プロピオン酸血症

• D-メチルマロニルCoA　－－(methylmalonyl-CoA racemase)－→　L-メチルマロニルCoA
• L-メチルマロニルCoA　－－(methylmalonyl-CoA isomerase/methylmalonyl-CoA mutase+ビタミンB12)－→　サクシニルCoA

→メチルマロン酸尿症

誘導体

• イブプロフェン、ナプロキセン、ロキソプロフェンナトリウムなど、Α炭素に芳香族部位が置換した非ステロイド性抗炎症薬 (NSAIDs) が知られ、「プロピオン酸系」と称される。

臨床関連

• メチルマロン酸尿症 methylmalonic aciduria：
• プロピオン酸血症 propionic acidemia：

「プロピオニルCoA」

　　[★]

英

propionyl CoA

関

[[]]

• プロピオニルCoA propionyl CoA

• プロピオニルCoAカルボキシラーゼ propionyl-CoA carboxylase：ビオチン

• (S)-メチルマロニルCoA (S)-methylmaronyl-CoA

• メチルマロニルCoAエピメラーゼ methylmalonyl-CoA epimerase

• (R)-メチルマロニルCoA (R)-methylmaronyl-CoA

• メチルマロニルCoAムターゼ methylmalonyl-CoA mutase：ビタミンB12

• スクシニルCoA succinyl-CoA

同

propiony卜CoA

「メチルマロニルCoAムターゼ」

　　[★]

malonyl

英

methylmalonyl-CoA mutase

関

プロピオニルCoA

• 奇数炭素脂肪酸の酸化に関与
• (R)-メチルマロニルCoAをスクシニルCoAに転換する
• 補酵素：ビタミンB12

• ビタミンB12の不足によりmethylmalonicaciduriaを呈する

「C」

　　[★]

• 炭素 carbon
• シトシン cytosine
• システイン cysteine
• シチジン
• セルシウス度 摂氏 degrees Celsius degree C
• 産婦人科領域で「子宮外頚 子宮外頚部 exocervix」を表現するための略語

　 　 　 　

「CoA」

　　[★]

• 大動脈縮窄症 coactation of the aorta
• 補酵素A coenzyme A

「mutase」

　　[★]

ムターゼ

関

intramolecular transferase

「COA」

　　[★] 補酵素A coenzyme A CoA

「Co」

　　[★] コバルト cobalt