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discounted EARLY registration ends Dec 31, 2014
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Metabolic Modeling Tutorial
discounted EARLY registration ends Dec 31, 2014
BioCyc websites down
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Metabolic Modeling Tutorial
discounted EARLY registration ends Dec 31, 2014
BioCyc websites down
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MetaCyc Enzyme: α-methylacyl-CoA racemase

Gene: Amacr Accession Number: G-10921 (MetaCyc)

Species: Rattus norvegicus

Summary:
Racemization of (25R)-3α,7α,12α-trihydroxy-5β-cholestanoyl-CoA to (25S)-3α,7α,12α-trihydroxy-5β-cholestanoyl-CoA is considered to be necessary for subsequent peroxisomal side chain shortening to occur during normal bile acid biosynthesis (reviewed in [Russell03]).

In humans, mutations in the gene encoding this enzyme can result in neonatal liver disease and adult motor neuropathy [Setchell03] and reviewed in [Russell03].

An apparent molecular mass of 44.9 kDa was determined by SDS-PAGE and 44.7 kDa by gel filtration chromatography, indicating a monomeric structure [Schmitz94].

Recombinant enzyme has been expressed in Escherichia coli [Schmitz97].

Map Position: [60,332,292 -> 60,344,326]

Molecular Weight of Polypeptide: 41.828 kD (from nucleotide sequence), 44.9 kD (experimental) [Schmitz94 ]

pI: 6.1 [Schmitz94]

Unification Links: Entrez-gene:25284 , Pride:P70473 , Protein Model Portal:P70473 , String:P70473 , UniProt:P70473

Relationship Links: InterPro:IN-FAMILY:IPR003673 , InterPro:IN-FAMILY:IPR023606 , Panther:IN-FAMILY:PTHR11837 , Pfam:IN-FAMILY:PF02515

Gene-Reaction Schematic: ?

Credits:
Created 22-Oct-2008 by Fulcher CA , SRI International


Enzymatic reaction of: (25R)-3α,7α-dihydroxy-5β-cholestanoyl-CoA racemase (α-methylacyl-CoA racemase)

(25R)-3α,7α-dihydroxy-5β-cholestanoyl-CoA <=> (25S)-3α,7α-dihydroxy-5β-cholestanoyl-CoA

The reaction direction shown, that is, A + B ↔ C + D versus C + D ↔ A + B, is in accordance with the Enzyme Commission system.

This reaction is reversible.

In Pathways: bile acid biosynthesis, neutral pathway


Enzymatic reaction of: (25R)-3α,7α,12α-trihydroxy-5β-cholestanoyl-CoA racemase (α-methylacyl-CoA racemase)

Synonyms: 2-methylacyl-CoA 2-epimerase, 2-methylacyl-CoA racemase, 2-arylpropionyl-CoA epimerase

(25R)-3α,7α,12α-trihydroxy-5β-cholestanoyl-CoA <=> (25S)-3α,7α,12α-trihydroxy-5β-cholestanoyl-CoA

The reaction direction shown, that is, A + B ↔ C + D versus C + D ↔ A + B, is in accordance with the direction of enzyme catalysis.

This reaction is reversible. [Ikegawa95]

Alternative Substrates for (25R)-3α,7α,12α-trihydroxy-5β-cholestanoyl-CoA: (25R)-3α,7α-dihydroxy-5β-cholestanoyl-CoA [Schmitz97 ]

In Pathways: bile acid biosynthesis, neutral pathway

Summary:
The enzyme uses only CoA thioesters of fatty acids, bile acid intermediates and some xenobiotics as substrates, but acts on a wide variety of α-methylacyl-CoAs [Schmitz94, Reichel95].

The racemization of pristanoyl-CoA was inhibited by compounds indicated below [Schmitz94].

Inhibitors (Unknown Mechanism): diisopropyl fluorophosphate [Schmitz94] , Hg2+ [Schmitz94] , Cu2+ [Schmitz94] , 5,5'-dithio-bis-2-nitrobenzoate [Schmitz94]

pH(opt): 6-7 [Schmitz94]


References

Ikegawa95: Ikegawa S, Goto T, Watanabe H, Goto J (1995). "Stereoisomeric inversion of (25R)- and (25S)-3 alpha,7 alpha,12 alpha-trihydroxy-5 beta-cholestanoic acids in rat liver peroxisome." Biol Pharm Bull 18(7);1027-9. PMID: 7581245

Reichel95: Reichel C, Bang H, Brune K, Geisslinger G, Menzel S (1995). "2-Arylpropionyl-CoA epimerase: partial peptide sequences and tissue localization." Biochem Pharmacol 50(11);1803-6. PMID: 8615858

Russell03: Russell DW (2003). "The enzymes, regulation, and genetics of bile acid synthesis." Annu Rev Biochem 72;137-74. PMID: 12543708

Schmitz94: Schmitz W, Fingerhut R, Conzelmann E (1994). "Purification and properties of an alpha-methylacyl-CoA racemase from rat liver." Eur J Biochem 222(2);313-23. PMID: 8020470

Schmitz97: Schmitz W, Helander HM, Hiltunen JK, Conzelmann E (1997). "Molecular cloning of cDNA species for rat and mouse liver alpha-methylacyl-CoA racemases." Biochem J 326 ( Pt 3);883-9. PMID: 9307041

Setchell03: Setchell KD, Heubi JE, Bove KE, O'Connell NC, Brewsaugh T, Steinberg SJ, Moser A, Squires RH (2003). "Liver disease caused by failure to racemize trihydroxycholestanoic acid: gene mutation and effect of bile acid therapy." Gastroenterology 124(1);217-32. PMID: 12512044


Report Errors or Provide Feedback
Please cite the following article in publications resulting from the use of MetaCyc: Caspi et al, Nucleic Acids Research 42:D459-D471 2014
Page generated by SRI International Pathway Tools version 18.5 on Mon Dec 22, 2014, biocyc14.