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MetaCyc Enzyme: fatty acid oxidation complex, α component

Gene: fadB Accession Numbers: EG10279 (MetaCyc), b3846, ECK3838

Synonyms: oldB

Species: Escherichia coli K-12 substr. MG1655

Component of: aerobic fatty acid oxidation complex

Subunit composition of fatty acid oxidation complex, α component = [FadB]2
         dodecenoyl-CoA δ-isomerase, enoyl-CoA hydratase, 3-hydroxybutyryl-CoA epimerase, 3-hydroxyacyl-CoA dehydrogenase = FadB

Summary:
The alpha subunit has four enzymatic activities associated with it. It is part of a multienzyme complex. Two of the activities, enoyl-CoA hydratase (EC 4.2.1.17) and 3-OHacyl-CoA epimerase (EC 5.1.2.3) are carried out by the same N terminal active site. [Yang93]

Locations: cytosol

Map Position: [4,026,805 <- 4,028,994]

Molecular Weight of Polypeptide: 79.594 kD (from nucleotide sequence)

pI: 6.16

Unification Links: ASAP:ABE-0012564 , CGSC:793 , DIP:DIP-9560N , EchoBASE:EB0275 , EcoGene:EG10279 , EcoliWiki:b3846 , ModBase:P21177 , OU-Microarray:b3846 , PortEco:fadB , Pride:P21177 , Protein Model Portal:P21177 , RefSeq:NP_418288 , RegulonDB:EG10279 , SMR:P21177 , String:511145.b3846 , Swiss-Model:P21177 , UniProt:P21177

Relationship Links: InterPro:IN-FAMILY:IPR001753 , InterPro:IN-FAMILY:IPR006108 , InterPro:IN-FAMILY:IPR006176 , InterPro:IN-FAMILY:IPR006180 , InterPro:IN-FAMILY:IPR008927 , InterPro:IN-FAMILY:IPR012799 , InterPro:IN-FAMILY:IPR013328 , InterPro:IN-FAMILY:IPR016040 , InterPro:IN-FAMILY:IPR018376 , Pfam:IN-FAMILY:PF00378 , Pfam:IN-FAMILY:PF00725 , Pfam:IN-FAMILY:PF02737 , Prosite:IN-FAMILY:PS00067 , Prosite:IN-FAMILY:PS00166

Gene-Reaction Schematic: ?

Instance reaction of [a cis-3-enoyl-CoA ↔ a trans-2-enoyl-CoA] (5.3.3.8):
i5: 3-cis-dodecenoyl-CoA → 2-trans-dodecenoyl-CoA (5.3.3.8)

Instance reactions of [a 2,3,4-saturated fatty acyl CoA + acetyl-CoA ↔ a 3-oxoacyl-CoA + coenzyme A] (2.3.1.16):
i13: acetyl-CoA + propanoyl-CoA = β-ketovaleryl-CoA + coenzyme A (2.3.1.9)

i14: decanoyl-CoA + acetyl-CoA = 3-oxododecanoyl-CoA + coenzyme A (2.3.1.16)

i15: octanoyl-CoA + acetyl-CoA ← 3-oxodecanoyl-CoA + coenzyme A (2.3.1.16)

i16: hexanoyl-CoA + acetyl-CoA = 3-oxooctanoyl-CoA + coenzyme A (2.3.1.16)

i17: acetyl-CoA + myristoyl-CoA = 3-oxo-palmitoyl-CoA + coenzyme A (2.3.1.155)

i18: butanoyl-CoA + acetyl-CoA → 3-oxohexanoyl-CoA + coenzyme A (2.3.1.16)

Instance reactions of [a (3S)-3-hydroxyacyl-CoA ← a trans-2-enoyl-CoA + H2O] (4.2.1.17):
i1: (3R)-3-hydroxy-lignoceroyl-CoA → trans-lignocer-2-enoyl-CoA + H2O (4.2.1.134)

i2: (S)-3-hydroxybutanoyl-CoA ↔ crotonyl-CoA + H2O (4.2.1.150)

i3: (S)-3-hydroxydecanoyl-CoA ← trans-Δ2-decenoyl-CoA + H2O (4.2.1.17)

i4: (S)-3-hydroxyhexanoyl-CoA → trans-hex-2-enoyl-CoA + H2O (4.2.1.74)

Instance reactions of [a (3S)-3-hydroxyacyl-CoA + NAD+ ↔ a 3-oxoacyl-CoA + NADH + H+] (1.1.1.35):
i6: 3-hydroxy-5-cis-tetradecenoyl-CoA + NAD+ = 3-keto-5-cis-tetradecenoyl-CoA + NADH + H+ (1.1.1.211)

i7: (S)-3-hydroxytetradecanoyl-CoA + NAD+ = 3-oxo-myristoyl-CoA + NADH + H+ (no EC#)

i8: (S)-3-hydroxyhexadecanoyl-CoA + NAD+ = 3-oxo-palmitoyl-CoA + NADH + H+ (1.1.1.211)

i9: (S)-3-hydroxybutanoyl-CoA + NAD+ ↔ acetoacetyl-CoA + NADH + H+ (1.1.1.35)

i10: (S)-3-hydroxyoctanoyl-CoA + NAD+ = 3-oxooctanoyl-CoA + NADH + H+ (1.1.1.35)

i11: (S)-3-hydroxydecanoyl-CoA + NAD+ → 3-oxodecanoyl-CoA + NADH + H+ (1.1.1.35)

i12: (S)-3-hydroxyhexanoyl-CoA + NAD+ ← 3-oxohexanoyl-CoA + NADH + H+ (1.1.1.35)

GO Terms:

Biological Process: GO:0006635 - fatty acid beta-oxidation Inferred from experiment Inferred by computational analysis [UniProtGOA12, Pramanik79]
GO:0006629 - lipid metabolic process Inferred by computational analysis [UniProtGOA11]
GO:0006631 - fatty acid metabolic process Inferred by computational analysis [UniProtGOA11, GOA06, GOA01]
GO:0008152 - metabolic process Inferred by computational analysis [UniProtGOA11, GOA01]
GO:0009062 - fatty acid catabolic process Inferred by computational analysis [GOA01]
GO:0016042 - lipid catabolic process Inferred by computational analysis [UniProtGOA11, GOA06]
GO:0055114 - oxidation-reduction process Inferred by computational analysis [UniProtGOA11, GOA01]
Molecular Function: GO:0003857 - 3-hydroxyacyl-CoA dehydrogenase activity Inferred from experiment Inferred by computational analysis [GOA06, GOA01a, GOA01, He96a]
GO:0004165 - dodecenoyl-CoA delta-isomerase activity Inferred from experiment Inferred by computational analysis [GOA06, GOA01a, GOA01, Pramanik79]
GO:0004300 - enoyl-CoA hydratase activity Inferred from experiment Inferred by computational analysis [GOA06, GOA01a, GOA01, Yang93]
GO:0008692 - 3-hydroxybutyryl-CoA epimerase activity Inferred from experiment Inferred by computational analysis [GOA06, GOA01a, GOA01, Yang93]
GO:0003824 - catalytic activity Inferred by computational analysis [UniProtGOA11, GOA01]
GO:0016491 - oxidoreductase activity Inferred by computational analysis [UniProtGOA11, GOA01]
GO:0016616 - oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor Inferred by computational analysis [GOA01]
GO:0016829 - lyase activity Inferred by computational analysis [UniProtGOA11]
GO:0016853 - isomerase activity Inferred by computational analysis [UniProtGOA11]
GO:0050662 - coenzyme binding Inferred by computational analysis [GOA01]
Cellular Component: GO:0005829 - cytosol
GO:0036125 - fatty acid beta-oxidation multienzyme complex Inferred by computational analysis [GOA01]

MultiFun Terms: metabolism carbon utilization fatty acids

Credits:
Imported from EcoCyc 16-Sep-2014 by Paley S , SRI International


Enzymatic reaction of: 3-hydroxyacyl-CoA dehydrogenase (fatty acid oxidation complex, α component)

3-hydroxy-5-cis-tetradecenoyl-CoA + NAD+ <=> 3-keto-5-cis-tetradecenoyl-CoA + NADH + H+

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

Reversibility of this reaction is unspecified.

Credits:
Imported from EcoCyc 16-Sep-2014 by Paley S , SRI International

Summary:
Experimental work reported by [Ren04a] was conducted using E. coli strain B.


Enzymatic reaction of: 3-hydroxybutyryl-CoA epimerase (fatty acid oxidation complex, α component)

Synonyms: 3-hydroxyacyl-CoA epimerase, 3-hydroxybutanoyl-CoA 3-epimerase

a (3R)-3-hydroxyacyl-CoA <=> a (3S)-3-hydroxyacyl-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.

Alternative Substrates [Comment 1]:

In Pathways: fatty acid β-oxidation I

Credits:
Imported from EcoCyc 16-Sep-2014 by Paley S , SRI International

Summary:
This enzyme is part of a multienzyme complex that has broad substrate specificity. It is also part of a multifunctional polypeptide coded for by the fadB gene. This enzyme is required to feed some unsaturated fatty acids into the β-oxidation pathway. [Pramanik79] The active site for this reaction is also involved in the hydratase reaction (EC 4.2.1.17).

Regulators of Unknown Type: iodoacetamide [Yang83] , tris-hydrochloride [Pramanik79]


Enzymatic reaction of: 3-hydroxyacyl-CoA dehydrogenase (fatty acid oxidation complex, α component)

Synonyms: β-hydroxyacyl dehydrogenase, β-keto-reductase, (S)-3-hydroxyacyl-CoA:NAD+ oxidoreductase

EC Number: 1.1.1.35

a (3S)-3-hydroxyacyl-CoA + NAD+ <=> a 3-oxoacyl-CoA + NADH + H+

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.

Alternative Substrates for a (3S)-3-hydroxyacyl-CoA: a S-3-hydroxyacyl-N-acylthioethanolamine , a S-3-hydroxyacylhydrolipoate

In Pathways: photosynthetic 3-hydroxybutyrate biosynthesis (engineered) , pyruvate fermentation to hexanol , pyruvate fermentation to butanol II , (R)- and (S)-3-hydroxybutyrate biosynthesis , fatty acid β-oxidation I , methyl ketone biosynthesis

Credits:
Imported from EcoCyc 16-Sep-2014 by Paley S , SRI International

Summary:
This enzyme is part of a multienzyme complex that has broad substrate specificity. It is also part of a multifunctional polypeptide coded for by the fadB gene. This enzyme takes part in the oxidation of saturated fatty acids. It exhibits the highest activity with medium-chain substrates. [Binstock81] It also oxidizes S-3-hydroxyacyl-N-acylthioethanolamine and S-3-hydroxyacylhydrolipoate.

Regulators of Unknown Type: iodoacetamide [Yang83] , tris-hydrochloride [Pramanik79]


Enzymatic reaction of: enoyl-CoA hydratase (fatty acid oxidation complex, α component)

Synonyms: enoyl hydrase, unsaturated acyl-CoA hydratase, (3S)-3-hydroxyacyl-CoA hydro-lyase

EC Number: 4.2.1.17

a (3S)-3-hydroxyacyl-CoA <=> a trans-2-enoyl-CoA + H2O

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

The reaction is physiologically favored in the opposite direction.

EC Number: 4.2.1.17

2-trans,5-cis-tetradecadienoyl-CoA + H2O <=> 3-hydroxy-5-cis-tetradecenoyl-CoA

The reaction direction shown, that is, A + B ↔ C + D versus C + D ↔ A + B, is in accordance with the direction in which it was curated.

The reaction is favored in the direction shown.

Alternative Substrates [Comment 1]:

In Pathways: pyruvate fermentation to hexanol , pyruvate fermentation to butanol II , oleate β-oxidation , fatty acid β-oxidation I , methyl ketone biosynthesis

Credits:
Imported from EcoCyc 16-Sep-2014 by Paley S , SRI International

Summary:
This enzyme, a crotonase, is part of a multienzyme complex that has broad substrate specificity. It is also part of a multifunctional polypeptide coded for by the fadB gene. This enzyme takes part in the oxidation of saturated fatty acids. The enzyme is active with substrates of varying chain lengths. [Binstock81] The active site also catalyzes epimerization of unsaturated fatty acids (EC 5.1.2.3). [Yang93]

Regulators of Unknown Type: iodoacetamide [Yang83] , tris-hydrochloride [Pramanik79]


Enzymatic reaction of: Δ3-cis-Δ2-trans-enoyl-CoA isomerase (fatty acid oxidation complex, α component)

Synonyms: dodecenoyl-CoA δ-isomerase, enoyl-CoA δ-isomerase, acetylene-allene isomerase, dodecenoyl-CoA δ(3)-cis-δ(2)-trans-isomerase

a cis-3-enoyl-CoA <=> a trans-2-enoyl-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.

2-trans,5-cis-tetradecadienoyl-CoA <=> 3-trans,5-cis-tetradecadienoyl-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.

In Pathways: oleate β-oxidation , fatty acid β-oxidation III (unsaturated, odd number) , fatty acid β-oxidation I

Credits:
Imported from EcoCyc 16-Sep-2014 by Paley S , SRI International

Summary:
This enzyme is part of a multienzyme complex that has broad substrate specificity. It is also part of a multifunctional polypeptide coded for by the fadB gene. This enzyme is required when carbons 3,4 unsaturated fatty acids are degraded. [Pramanik79] It also catalyses the interconversion of 3-acetylenic fatty acyl thioesters and (+)-2,3-dienoyl fatty acyl thioesters, with fatty acid chain lengths C(6) to C(12).

Regulators of Unknown Type: N-ethylmaleimide [Pawar81] , iodoacetamide [Yang83] , tris-hydrochloride [Pramanik79]


Subunit of: aerobic fatty acid oxidation complex

Species: Escherichia coli K-12 substr. MG1655

Subunit composition of aerobic fatty acid oxidation complex = [(FadB)2][(FadA)2]
         fatty acid oxidation complex, α component = (FadB)2 (summary available)
                 dodecenoyl-CoA δ-isomerase, enoyl-CoA hydratase, 3-hydroxybutyryl-CoA epimerase, 3-hydroxyacyl-CoA dehydrogenase = FadB
         fatty acid oxidation complex, β component = (FadA)2
                 3-ketoacyl-CoA thiolase = FadA

Credits:
Imported from EcoCyc 16-Sep-2014 by Paley S , SRI International


Sequence Features

Feature Class Location Citations Comment
Protein-Segment 1 -> 189
[UniProt10a]
UniProt: Enoyl-CoA hydratase/isomerase; Sequence Annotation Type: region of interest;
Mutagenesis-Variant 116
[Yang93, UniProt14]
Alternate sequence: F; UniProt: Absence of both enoyl-CoA hydratase and 3-hydroxyacyl-CoA epimerase activities. Delta(3)-cis-Delta(2)-trans- enoyl-CoA isomerase is only slightly affected.
Amino-Acid-Site 119
[UniProt10a]
UniProt: Important for catalytic activity; Sequence Annotation Type: site; Non-Experimental Qualifier: by similarity;
Amino-Acid-Site 139
[UniProt10a]
UniProt: Important for catalytic activity; Sequence Annotation Type: site; Non-Experimental Qualifier: by similarity;
Amino-Acid-Sites-That-Bind 296
[UniProt10a]
UniProt: Substrate; Non-Experimental Qualifier: by similarity;
Protein-Segment 311 -> 729
[UniProt10a]
UniProt: 3-hydroxyacyl-CoA dehydrogenase; Sequence Annotation Type: region of interest;
Mutagenesis-Variant 322
[He96a, UniProt11]
Alternate sequence: A; UniProt: 10-fold increase in KM for NADH.
Amino-Acid-Sites-That-Bind 324
[UniProt10a]
UniProt: NAD; via amide nitrogen; Non-Experimental Qualifier: by similarity;
Amino-Acid-Sites-That-Bind 343
[UniProt10a]
UniProt: NAD; Non-Experimental Qualifier: by similarity;
Nucleotide-Phosphate-Binding-Region 400 -> 402
[UniProt10a]
UniProt: NAD; Non-Experimental Qualifier: by similarity;
Amino-Acid-Sites-That-Bind 407
[UniProt10a]
UniProt: NAD; Non-Experimental Qualifier: by similarity;
Nucleotide-Phosphate-Binding-Region 427 -> 429
[UniProt10a]
UniProt: NAD; Non-Experimental Qualifier: by similarity;
Mutagenesis-Variant 450
[He96a, UniProt11]
Alternate sequence: Q; UniProt: Almost complete loss of 3- hydroxyacyl-CoA dehydrogenase activity.
Alternate sequence: A; UniProt: Almost complete loss of 3- hydroxyacyl-CoA dehydrogenase activity.
Active-Site 450
[He96a, UniProt11]
UniProt: For 3-hydroxyacyl-CoA dehydrogenase activity.
Amino-Acid-Sites-That-Bind 453
[UniProt10a]
UniProt: NAD; Non-Experimental Qualifier: by similarity;
Amino-Acid-Sites-That-Bind 500
[UniProt10a]
UniProt: Substrate; Non-Experimental Qualifier: by similarity;
Sequence-Conflict 518
[DiRusso90, UniProt10]
Alternate sequence: R; UniProt: (in Ref. 1; AAA23750);
Amino-Acid-Sites-That-Bind 660
[UniProt10a]
UniProt: Substrate; Non-Experimental Qualifier: by similarity;
Sequence-Conflict 664
[Nakahigashi90, UniProt10]
Alternate sequence: L; UniProt: (in Ref. 3; CAB40809);
Sequence-Conflict 666
[Nakahigashi90, UniProt10]
Alternate sequence: A; UniProt: (in Ref. 3; CAB40809);

History:
10/20/97 Gene b3846 from Blattner lab Genbank (v. M52) entry merged into EcoCyc gene EG10279; confirmed by SwissProt match.


References

Binstock81: Binstock JF, Schulz H (1981). "Fatty acid oxidation complex from Escherichia coli." Methods Enzymol 1981;71 Pt C;403-11. PMID: 7024730

DiRusso90: DiRusso CC (1990). "Primary sequence of the Escherichia coli fadBA operon, encoding the fatty acid-oxidizing multienzyme complex, indicates a high degree of homology to eucaryotic enzymes." J Bacteriol 172(11);6459-68. PMID: 1699931

GOA01: GOA, DDB, FB, MGI, ZFIN (2001). "Gene Ontology annotation through association of InterPro records with GO terms."

GOA01a: GOA, MGI (2001). "Gene Ontology annotation based on Enzyme Commission mapping." Genomics 74;121-128.

GOA06: GOA, SIB (2006). "Electronic Gene Ontology annotations created by transferring manual GO annotations between orthologous microbial proteins."

He96a: He XY, Yang SY (1996). "Histidine-450 is the catalytic residue of L-3-hydroxyacyl coenzyme A dehydrogenase associated with the large alpha-subunit of the multienzyme complex of fatty acid oxidation from Escherichia coli." Biochemistry 1996;35(29);9625-30. PMID: 8755745

Nakahigashi90: Nakahigashi K, Inokuchi H (1990). "Nucleotide sequence of the fadA and fadB genes from Escherichia coli." Nucleic Acids Res 18(16);4937. PMID: 2204034

Pawar81: Pawar S, Schulz H (1981). "The structure of the multienzyme complex of fatty acid oxidation from Escherichia coli." J Biol Chem 1981;256(8);3894-9. PMID: 7012144

Pramanik79: Pramanik A, Pawar S, Antonian E, Schulz H (1979). "Five different enzymatic activities are associated with the multienzyme complex of fatty acid oxidation from Escherichia coli." J Bacteriol 1979;137(1);469-73. PMID: 368024

Ren04a: Ren Y, Aguirre J, Ntamack AG, Chu C, Schulz H (2004). "An alternative pathway of oleate beta-oxidation in Escherichia coli involving the hydrolysis of a dead end intermediate by a thioesterase." J Biol Chem 279(12);11042-50. PMID: 14707139

UniProt10: UniProt Consortium (2010). "UniProt version 2010-11 released on 2010-11-02 00:00:00." Database.

UniProt10a: UniProt Consortium (2010). "UniProt version 2010-07 released on 2010-06-15 00:00:00." Database.

UniProt11: UniProt Consortium (2011). "UniProt version 2011-06 released on 2011-06-30 00:00:00." Database.

UniProt14: UniProt Consortium (2014). "UniProt version 2014-01 released on 2014-01-01 00:00:00." Database.

UniProtGOA11: UniProt-GOA (2011). "Gene Ontology annotation based on manual assignment of UniProtKB keywords in UniProtKB/Swiss-Prot entries."

UniProtGOA12: UniProt-GOA (2012). "Gene Ontology annotation based on UniPathway vocabulary mapping."

Yang83: Yang SY, Schulz H (1983). "The large subunit of the fatty acid oxidation complex from Escherichia coli is a multifunctional polypeptide. Evidence for the existence of a fatty acid oxidation operon (fad AB) in Escherichia coli." J Biol Chem 1983;258(16);9780-5. PMID: 6350283

Yang91b: Yang XY, Schulz H, Elzinga M, Yang SY (1991). "Nucleotide sequence of the promoter and fadB gene of the fadBA operon and primary structure of the multifunctional fatty acid oxidation protein from Escherichia coli." Biochemistry 1991;30(27);6788-95. PMID: 1712230

Yang93: Yang SY, Elzinga M (1993). "Association of both enoyl coenzyme A hydratase and 3-hydroxyacyl coenzyme A epimerase with an active site in the amino-terminal domain of the multifunctional fatty acid oxidation protein from Escherichia coli." J Biol Chem 1993;268(9);6588-92. PMID: 8454629

Yang95: Yang SY, He XY, Schulz H (1995). "Glutamate 139 of the large alpha-subunit is the catalytic base in the dehydration of both D- and L-3-hydroxyacyl-coenzyme A but not in the isomerization of delta 3, delta 2-enoyl-coenzyme A catalyzed by the multienzyme complex of fatty acid oxidation from Escherichia coli." Biochemistry 1995;34(19);6441-7. PMID: 7756275


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 Tue Nov 25, 2014, biocyc14.