Metabolic Modeling Tutorial
discounted EARLY registration ends Dec 31, 2014
Metabolic Modeling Tutorial
discounted EARLY registration ends Dec 31, 2014
Metabolic Modeling Tutorial
discounted EARLY registration ends Dec 31, 2014
Metabolic Modeling Tutorial
discounted EARLY registration ends Dec 31, 2014
Metabolic Modeling Tutorial
discounted EARLY registration ends Dec 31, 2014
twitter

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 Fri Nov 28, 2014, BIOCYC13A.