BioPAX pathway converted from "Beta-oxidation of pristanoyl-CoA" in the Reactome database.

Beta-oxidation of pristanoyl-CoA

Pristanoyl-CoA, generated in the peroxisome by alpha-oxidation of dietary phytanic acid, is further catabolized by three cycles of peroxisomal beta-oxidation to yield 4,8-dimethylnonanoyl-CoA, acetyl-CoA and two molecules of propionyl-CoA. These molecules in turn are converted to carnitine conjugates, which can be transported to mitochondria (Wanders and Waterham 2006, Verhoeven et al. 1998, Ferdinandusse et al. 1999).

Authored: D'Eustachio, P, 2009-03-16 18:50:14Reviewed: Jassal, Bijay, 2009-02-27Edited: D'Eustachio, P, 2009-03-18 13:33:40

5.1.99.4

Isomerization of (2R)-pristanoyl-CoA to (2S)-pristanoyl-CoA

Peroxisomal 2-methylacyl-CoA racemase (AMACR) catalyzes the isomerization of (2R)-pristanoyl-CoA to form (2S)-pristanoyl-CoA. The active form of the enzyme is a monomer (Schmitz et al. 1995; Amery et al. 2000; Ferdinandusse et al. 2000).

Authored: D'Eustachio, P, 2009-03-16 18:50:14Reviewed: Jassal, Bijay, 2009-02-27Edited: D'Eustachio, P, 2009-03-18 13:33:40

Reactome DB_ID: 389569

peroxisomal matrixGO0005782

pristanoyl-CoA [ChEBI:51341]

pristanoyl-CoA

Reactomehttp://www.reactome.orgChEBI51341

Reactome DB_ID: 389893

(2S)-pristanoyl-CoA [ChEBI:64039]

(2S)-pristanoyl-CoA

(2S)-pristanoyl-coenzyme A(2S)-2,6,10,14-tetramethylpentadecanoyl-coenzyme A(2S)-2,6,10,14-tetramethylpentadecanoyl-CoA

ChEBI64039PHYSIOL-LEFT-TO-RIGHT

ACTIVATION

Reactome DB_ID: 192146

UniProt:Q9UHK6 AMACR

AMACR

AMACRFUNCTION Catalyzes the interconversion of (R)- and (S)-stereoisomers of alpha-methyl-branched-chain fatty acyl-CoA esters (PubMed:7649182, PubMed:10655068, PubMed:11060359). Acts only on coenzyme A thioesters, not on free fatty acids, and accepts as substrates a wide range of alpha-methylacyl-CoAs, including pristanoyl-CoA, trihydroxycoprostanoyl-CoA (an intermediate in bile acid synthesis), and arylpropionic acids like the anti-inflammatory drug ibuprofen (2-(4-isobutylphenyl)propionic acid) but neither 3-methyl-branched nor linear-chain acyl-CoAs (PubMed:7649182, PubMed:10655068, PubMed:11060359).PATHWAY Lipid metabolism; bile acid biosynthesis.PATHWAY Lipid metabolism; fatty acid metabolism.SUBUNIT Monomer.SIMILARITY Belongs to the CoA-transferase III family.

Homo sapiens

NCBI Taxonomy9606UniProtQ9UHK6

Chain Coordinates

EQUAL

382

EQUAL

GO0008111

GO molecular function

Reactome Database ID Release 75191973Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=191973Reactome Database ID Release 75389897Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=389897ReactomeR-HSA-389897

Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-389897.17649182Pubmed1995Purification and characterization of an alpha-methylacyl-CoA racemase from human liverSchmitz, WAlbers, CFingerhut, RConzelmann, EEur J Biochem 231:815-2211060359Pubmed2000Subcellular localization and physiological role of alpha-methylacyl-CoA racemaseFerdinandusse, SachaDenis, SimoneIJlst, LDacremont, GeorgesWaterham, HRWanders, Ronald J AJ Lipid Res 41:1890-611060344Pubmed2000Mitochondrial and peroxisomal targeting of 2-methylacyl-CoA racemase in humansAmery, LFransen, MDe Nys, KMannaerts, Guy PVan Veldhoven, Paul PJ Lipid Res 41:1752-9

1.3.3

ACOX2:FAD, ACOXL:FAD oxidise (2S)-pristanoyl-CoA to trans-2,3-dehydropristanoyl-CoA

(2S)-pristanoyl-CoA + O2 => trans-2,3-dehydropristanoyl-CoA + H2O2 (ACOX2)In human liver and kidney tissue, monomeric peroxisomal ACOX2 (bound to FAD cofactor) catalyzes the reaction of (2S)-pristanoyl-CoA and O2 to form trans-2,3-dehydropristanoyl-CoA and H2O2 (Vanhove et al. 1993; Baumgart et al. 1996). A putative acyl-coenzyme A oxidase-like protein ACOXL could catalyse this type of reaction but its activity has not yet been determined.

Authored: D'Eustachio, P, 2009-03-16 18:50:14Reviewed: Jassal, Bijay, 2009-02-27Edited: D'Eustachio, P, 2009-03-18 13:33:40

Reactome DB_ID: 389893

Reactome DB_ID: 113535

dioxygen [ChEBI:15379]

dioxygen

ChEBI15379

Reactome DB_ID: 389894

(E)-2,3-didehydropristanoyl-CoA [ChEBI:63803]

(E)-2,3-didehydropristanoyl-CoA

trans-2,3-dehydropristanoyl-CoAtrans-2,3-didehydropristanoyl-CoA

ChEBI63803

Reactome DB_ID: 113575

hydrogen peroxide [ChEBI:16240]

hydrogen peroxide

ChEBI16240PHYSIOL-LEFT-TO-RIGHT

ACTIVATION

Converted from EntitySet in Reactome

Reactome DB_ID: 8848531

ACOX2:FAD, ACOXL:FAD [peroxisomal matrix]Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntity

GO0016402

GO molecular function

Reactome Database ID Release 75389900Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=389900Reactome Database ID Release 75389889Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=389889ReactomeR-HSA-389889

Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-389889.28943006Pubmed1996Molecular characterization of the human peroxisomal branched-chain acyl-CoA oxidase: cDNA cloning, chromosomal assignment, tissue distribution, and evidence for the absence of the protein in Zellweger syndromeBaumgart, EVanhooren, JCFransen, MMarynen, PPuype, MVandekerckhove, JLeunissen, JAFahimi, HDMannaerts, Guy PVan Veldhoven, Paul PProc Natl Acad Sci U S A 93:13748-538387517Pubmed1993The CoA esters of 2-methyl-branched chain fatty acids and of the bile acid intermediates di- and trihydroxycoprostanic acids are oxidized by one single peroxisomal branched chain acyl-CoA oxidase in human liver and kidneyVanhove, GFVan Veldhoven, Paul PFransen, MDenis, SimoneEyssen, HJWanders, Ronald J AMannaerts, Guy PJ Biol Chem 268:10335-44

1.3.3

(2S)-pristanoyl-CoA + O2 => trans-2,3-dehydropristanoyl-CoA + H2O2 (ACOX3)

Peroxisomal ACOX3 catalyzes the reaction of (2S)-pristanoyl-CoA and O2 to form trans-2,3-dehydropristanoyl-CoA and H2O2. ACOX3 protein and enzyme activity have been observed in prostate tumors, but are undetectable in normal prostate tissue as well as in liver and kidney (where ACOX2 catalyzes the oxidation of pristanoyl-CoA) (Zha et al. 2005; Vanhooren et al. 1997). The physiological consequences of this differential gene expression are unknown.

Authored: D'Eustachio, P, 2009-03-16 18:50:14Reviewed: Jassal, Bijay, 2009-02-27Edited: D'Eustachio, P, 2009-03-18 13:33:40

Reactome DB_ID: 389893

Reactome DB_ID: 113535

Reactome DB_ID: 389894

Reactome DB_ID: 113575

PHYSIOL-LEFT-TO-RIGHT

ACTIVATION

Reactome DB_ID: 389905

ACOX3:FAD [peroxisomal matrix]

ACOX3:FAD

Acyl-CoA oxidase 3 (FAD cofactor)

Reactome DB_ID: 141335

FAD [ChEBI:16238]

FAD

Flavin adenine dinucleotide

ChEBI16238

Reactome DB_ID: 389884

UniProt:O15254 ACOX3

ACOX3

BRCOXPRCOXACOX3FUNCTION Oxidizes the CoA-esters of 2-methyl-branched fatty acids.PATHWAY Lipid metabolism; peroxisomal fatty acid beta-oxidation.SIMILARITY Belongs to the acyl-CoA oxidase family.

UniProtO15254

EQUAL

700

EQUAL

Reactome Database ID Release 75389905Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=389905ReactomeR-HSA-389905

Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-389905.1Reactome Database ID Release 75389903Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=389903Reactome Database ID Release 75389891Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=389891ReactomeR-HSA-389891

Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-389891.19271077Pubmed1997Evidence for the existence of a pristanoyl-CoA oxidase gene in manVanhooren, JCMarynen, PMannaerts, Guy PVan Veldhoven, Paul PBiochem J 325:593-915599942Pubmed2005Peroxisomal branched chain fatty acid beta-oxidation pathway is upregulated in prostate cancerZha, SFerdinandusse, SachaHicks, JLDenis, SimoneDunn, TAWanders, Ronald J ALuo, JDe Marzo, AMIsaacs, WBProstate 63:316-23

4.2.1.74

trans-2,3-dehydropristanoyl-CoA + H2O => 3-hydroxypristanoyl-CoA

Peroxisomal HSD17B4 dimer catalyzes the reaction of trans-2,3-dehydropristanoyl-CoA and H2O to form 3-hydroxypristanoyl-CoA. The enzyme is bifunctional - an aminoterminal domain catalyzes the dehydrogenation of a variety of 3-hydroxyacyl-CoA's and a carboxyterminal domain catalyzes the hydration of a variety of trans-2,3-dehydroacyl-CoA's, the reaction annotated here (Jiang et al. 1996, 1997). Defects in the enzyme are associated with a severe disorder of peroxisomal fatty acid metabolism in humans (Ferdinandusse et al. 2006).

Authored: D'Eustachio, P, 2009-03-16 18:50:14Reviewed: Jassal, Bijay, 2009-02-27Edited: D'Eustachio, P, 2009-03-18 13:33:40

Reactome DB_ID: 389894

Reactome DB_ID: 141343

water [ChEBI:15377]

water

ChEBI15377

Reactome DB_ID: 389982

3-hydroxypristanoyl-CoA [ChEBI:63914]

3-hydroxypristanoyl-CoA

3-hydroxy-2,6,10,14-tetramethylpentadecanoyl-coenzyme A3-hydroxypristanoyl-coenzyme A3-hydroxy-2,6,10,14-tetramethylpentadecanoyl-CoA

ChEBI63914PHYSIOL-LEFT-TO-RIGHT

ACTIVATION

Reactome DB_ID: 389999

HSD17B4 dimer [peroxisomal matrix]

HSD17B4 dimer

Peroxisomal multifunctional enzyme type 2 dimer

Reactome DB_ID: 192322

UniProt:P51659 HSD17B4

HSD17B4

SDR8C1EDH17B4HSD17B4FUNCTION Bifunctional enzyme acting on the peroxisomal beta-oxidation pathway for fatty acids. Catalyzes the formation of 3-ketoacyl-CoA intermediates from straight-chain, 2-methyl-branched-chain fatty acids bile acid intermediates. With EHHADH, catalyzes the hydration of trans-2-enoyl-CoA and the dehydrogenation of 3-hydroxyacyl-CoA, but with opposite chiral specificity (PubMed:10671535).PATHWAY Lipid metabolism; fatty acid beta-oxidation.SUBUNIT Homodimer.TISSUE SPECIFICITY Present in many tissues with highest concentrations in liver, heart, prostate and testis.MISCELLANEOUS The protein is found both as a full-length peptide and in a cleaved version.SIMILARITY Belongs to the short-chain dehydrogenases/reductases (SDR) family.

UniProtP51659

EQUAL

736

EQUAL

Reactome Database ID Release 75389999Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=389999ReactomeR-HSA-389999

Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-389999.1GO0016508

GO molecular function

Reactome Database ID Release 75389989Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=389989Reactome Database ID Release 75389986Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=389986ReactomeR-HSA-389986

Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-389986.19089413Pubmed1997Structure of D-3-hydroxyacyl-CoA dehydratase/D-3-hydroxyacyl-CoA dehydrogenase bifunctional proteinJiang, LLMiyazawa, SSouri, MHashimoto, TakashiJ Biochem 121:364-916385454Pubmed2006Mutational spectrum of D-bifunctional protein deficiency and structure-based genotype-phenotype analysisFerdinandusse, SachaYlianttila, MSGloerich, JoleinKoski, MKOostheim, WWaterham, HRHiltunen, J KalervoWanders, Ronald J AGlumoff, TAm J Hum Genet 78:112-248902629Pubmed1996Purification and properties of human D-3-hydroxyacyl-CoA dehydratase: medium-chain enoyl-CoA hydratase is D-3-hydroxyacyl-CoA dehydrataseJiang, LLKobayashi, AMatsuura, HFukushima, HHashimoto, TakashiJ Biochem (Tokyo) 120:624-32

1.1.1.35

3-hydroxypristanoyl-CoA + NAD+ => 3-ketoxypristanoyl-CoA + NADH + H+

Peroxisomal HSD17B4 dimer catalyzes the reaction of 3-hydroxypristanoyl-CoA and NAD+ to form 3-ketoxypristanoyl-CoA and NADH + H+. The enzyme is bifunctional - an aminoterminal domain catalyzes the dehydrogenation of a variety of 3-hydroxyacyl-CoA's, the reaction annotated here, and a carboxyterminal domain catalyzes the hydration of a variety of trans-2,3-dehydroacyl-CoA's (Jiang et al. 1996, 1997). Defects in the enzyme are associated with a severe disorder of peroxisomal fatty acid metabolism in humans (Ferdinandusse et al. 2006).

Authored: D'Eustachio, P, 2009-03-16 18:50:14Reviewed: Jassal, Bijay, 2009-02-27Edited: D'Eustachio, P, 2009-03-18 13:33:40

Reactome DB_ID: 389982

Reactome DB_ID: 192307

NAD(1-) [ChEBI:57540]

NAD(1-)

NAD(+)adenosine 5'-{3-[1-(3-carbamoylpyridinio)-1,4-anhydro-D-ribitol-5-yl] diphosphate}NAD anion

ChEBI57540

Reactome DB_ID: 389996

3-oxopristanoyl-CoA [ChEBI:15371]

3-oxopristanoyl-CoA

ChEBI15371

Reactome DB_ID: 192305

NADH(2-) [ChEBI:57945]

NADH(2-)

NADH dianionadenosine 5'-{3-[1-(3-carbamoyl-1,4-dihydropyridin-1-yl)-1,4-anhydro-D-ribitol-5-yl] diphosphate}NADH

ChEBI57945

Reactome DB_ID: 193465

hydron [ChEBI:15378]

hydron

ChEBI15378PHYSIOL-LEFT-TO-RIGHT

ACTIVATION

Reactome DB_ID: 389999

GO0003857

GO molecular function

Reactome Database ID Release 75193365Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=193365Reactome Database ID Release 75389995Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=389995ReactomeR-HSA-389995

Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-389995.1

2.3.1.176

3-ketopristanoyl-CoA + CoASH => 4,8,12-trimethyltridecanoyl-CoA + propionyl-CoA

Peroxisomal SCPx (Non-specific lipid transfer protein; SCP2) catalyzes the reaction of 3-ketopristanoyl-CoA and CoASH to form 4,8,12-trimethyltridecanoyl-CoA and propionyl-CoA. Both intact SCPx and an SCPx fragment corresponding to approximately the 430 aminoterminal residues of the protein are catalytically active in vitro; the latter form may predominate in vivo. Consistent with the role of SCPx in the beta-oxidation of branched-chain fatty acids in vitro, mutations in the protein are associated with elevated levels of pristanic acid in the blood in vivo and the development of neurological defects (Ferdinandusse et al. 2000, 2006).

Authored: D'Eustachio, P, 2009-03-16 18:50:14Reviewed: Jassal, Bijay, 2009-02-27Edited: D'Eustachio, P, 2009-03-18 13:33:40

Reactome DB_ID: 389996

Reactome DB_ID: 193514

coenzyme A [ChEBI:15346]

coenzyme A

ChEBI15346

Reactome DB_ID: 390002

4,8,12-trimethyltridecanoyl-CoA [ChEBI:15495]

4,8,12-trimethyltridecanoyl-CoA

ChEBI15495

Reactome DB_ID: 192314

propionyl-CoA [ChEBI:15539]

propionyl-CoA

ChEBI15539PHYSIOL-LEFT-TO-RIGHT

ACTIVATION

Reactome DB_ID: 192348

UniProt:P22307-1 SCP2

SCP2

SCP2FUNCTION Mediates in vitro the transfer of all common phospholipids, cholesterol and gangliosides between membranes. May play a role in regulating steroidogenesis.SUBUNIT Interacts with PEX5.TISSUE SPECIFICITY Liver, fibroblasts, and placenta.INDUCTION Up-regulated by 4-hydroxy-tamoxifen.SIMILARITY In the N-terminal section; belongs to the thiolase-like superfamily. Thiolase family.

UniProtP22307-1

EQUAL

547

EQUAL

GO0050632

GO molecular function

Reactome Database ID Release 75192310Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=192310Reactome Database ID Release 75390224Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=390224ReactomeR-HSA-390224

Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-390224.110706581Pubmed2000Peroxisomal fatty acid oxidation disorders and 58 kDa sterol carrier protein X (SCPx). Activity measurements in liver and fibroblasts using a newly developed method.Ferdinandusse, SachaDenis, Simonevan Berkel, EDacremont, GeorgesWanders, Ronald J AJ Lipid Res 41:336-4216685654Pubmed2006Mutations in the gene encoding peroxisomal sterol carrier protein X (SCPx) cause leukencephalopathy with dystonia and motor neuropathyFerdinandusse, SachaKostopoulos, PDenis, SimoneRusch, HOvermars, HDillmann, UReith, WHaas, DWanders, Ronald J ADuran, MMarziniak, MAm J Hum Genet 78:1046-52

4,8,12-trimethyltridecanoyl-CoA + 2 O2 + 2 H2O + 2 NAD+ + 2 CoASH => 4,8-dimethylnonanoyl-CoA + 2 H2O2 + 2 NADH + 2 H+ + acetyl-CoA + propionyl-CoA

In two cycles of beta-oxidation mediated by the same enzyme activities responsible for the conversion of pristanoyl-CoA to 4,8,12-trimethyltridecanoyl-CoA, the latter molecule is converted to 4,8-dimethylnonanoyl-CoA. Two molecules each of O2, H2O, NAD+, and CoASH are consumed in the process and two molecules of H2O2 and NADH + H+ are generated, together with single molecules of acetyl-CoA and propionyl-CoA (Verhoeven et al. 1998).

Authored: D'Eustachio, P, 2009-03-16 18:50:14Reviewed: Jassal, Bijay, 2009-02-27

Reactome DB_ID: 141343

Reactome DB_ID: 390002

Reactome DB_ID: 193514

Reactome DB_ID: 192307

Reactome DB_ID: 113535

Reactome DB_ID: 353123

acetyl-CoA [ChEBI:15351]

acetyl-CoA

ChEBI15351

Reactome DB_ID: 390271

4,8-dimethylnonanoyl-CoA [ChEBI:63856]

4,8-dimethylnonanoyl-CoA

4,8-dimethylnonanoyl-Coenzyme A

ChEBI63856

Reactome DB_ID: 192305

Reactome DB_ID: 193465

Reactome DB_ID: 113575

Reactome DB_ID: 192314

Reactome Database ID Release 75390276Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=390276ReactomeR-HSA-390276

Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-390276.19469587Pubmed1998Phytanic acid and pristanic acid are oxidized by sequential peroxisomal and mitochondrial reactions in cultured fibroblastsVerhoeven, Nanda MRoe, DSKok, RMWanders, Ronald J AJakobs, CornelisRoe, CRJ Lipid Res 39:66-74

2.3.1.137

4,8-dimethylnonanoyl-CoA + carnitine => 4,8-dimethylnonanoylcarnitine + CoASH

Peroxisomal CROT catalyzes the reaction of 4,8-dimethylnonanoyl-CoA and carnitine to form 4,8-dimethylnonanoylcarnitine and CoASH (Ferdinandusse et al. 1999).

Authored: D'Eustachio, P, 2009-03-16 18:50:14Reviewed: Jassal, Bijay, 2009-02-27Edited: D'Eustachio, P, 2009-03-18 13:33:40

Reactome DB_ID: 390294

carnitine [ChEBI:17126]

carnitine

ChEBI17126

Reactome DB_ID: 390271

Reactome DB_ID: 193514

Reactome DB_ID: 390290

O-(4,8-dimethylnonanoyl)carnitine [ChEBI:63874]

O-(4,8-dimethylnonanoyl)carnitine

4,8-dimethylnonanoylcarnitine

ChEBI63874PHYSIOL-LEFT-TO-RIGHT

ACTIVATION

Reactome DB_ID: 390296

UniProt:Q9UKG9 CROT

CROT

COTCROTFUNCTION Beta-oxidation of fatty acids. The highest activity concerns the C6 to C10 chain length substrate. Converts the end product of pristanic acid beta oxidation, 4,8-dimethylnonanoyl-CoA, to its corresponding carnitine ester.PATHWAY Lipid metabolism; fatty acid beta-oxidation.SUBUNIT Monomer.SIMILARITY Belongs to the carnitine/choline acetyltransferase family.

UniProtQ9UKG9

EQUAL

612

EQUAL

GO0008458

GO molecular function

Reactome Database ID Release 75390282Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=390282Reactome Database ID Release 75390281Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=390281ReactomeR-HSA-390281

Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-390281.110486279Pubmed1999Molecular cloning and expression of human carnitine octanoyltransferase: evidence for its role in the peroxisomal beta-oxidation of branched-chain fatty acidsFerdinandusse, SachaMulders, JIJlst, LDenis, SimoneDacremont, GeorgesWaterham, HRWanders, Ronald J ABiochem Biophys Res Commun 263:213-8

2.3.1.7

acetyl-CoA + carnitine => acetylcarnitine + CoASH

Peroxisomal carnitineacetyltransferase (CRAT) catalyzes the reaction of acetyl-CoA and carnitine to form acetylcarnitine and CoASH. The active form of the enzyme is a monomer (Bloisi et al. 1990; Wu et al. 2003).

Authored: D'Eustachio, P, 2009-03-16 18:50:14Reviewed: Jassal, Bijay, 2009-02-27Edited: D'Eustachio, P, 2009-03-18 13:33:40

Reactome DB_ID: 390294

Reactome DB_ID: 353123

Reactome DB_ID: 390287

O-acetylcarnitinium [ChEBI:15960]

O-acetylcarnitinium

ChEBI15960

Reactome DB_ID: 193514

PHYSIOL-LEFT-TO-RIGHT

ACTIVATION

Reactome DB_ID: 390293

UniProt:P43155 CRAT

CRAT

CAT1CRATFUNCTION Catalyzes the reversible transfer of acyl groups from carnitine to coenzyme A (CoA) and regulates the acyl-CoA/CoA ratio. Also plays a crucial role in the transport of fatty acids for beta-oxidation (PubMed:15099582, PubMed:29395073). Responsible for the synthesis of short- and branched-chain acylcarnitines (PubMed:23485643). Active towards some branched-chain amino acid oxidation pathway (BCAAO) intermediates (PubMed:23485643). Trans-2-enoyl-CoAs and 2-methylacyl-CoAs are poor substrates (PubMed:23485643).SUBUNIT Monomer.TISSUE SPECIFICITY Mostly in skeletal muscle, less in heart, liver and pancreas, only weakly detectable in brain, placenta, lung and kidney.SIMILARITY Belongs to the carnitine/choline acetyltransferase family.

UniProtP43155

EQUAL

626

EQUAL

GO0004092

GO molecular function

Reactome Database ID Release 75390278Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=390278Reactome Database ID Release 75390291Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=390291ReactomeR-HSA-390291

Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-390291.112562770Pubmed2003Structure of human carnitine acetyltransferase. Molecular basis for fatty acyl transfer.Wu, DGovindasamy, LLian, WGu, YKukar, TAgbandje-McKenna, MMcKenna, RJ Biol Chem 278:13159-652351134Pubmed1990Purification and properties of carnitine acetyltransferase from human liverBloisi, WColombo, IGaravaglia, BGiardini, RFinocchiaro, GDiDonato, SEur J Biochem 189:539-46

3.1.2.1

acetyl-CoA + H2O => acetate + CoASH

Peroxisomal ACOT8 catalyzes the hydrolysis of acetyl-CoA to form acetate and CoASH (Jones et al. 1999; Wanders and Waterham 2006).

Authored: D'Eustachio, P, 2009-03-16 18:50:14Reviewed: Jassal, Bijay, 2009-02-27Edited: D'Eustachio, P, 2009-03-18 13:33:40

Reactome DB_ID: 353123

Reactome DB_ID: 141343

Reactome DB_ID: 390305

acetic acid [ChEBI:15366]

acetic acid

ChEBI15366

Reactome DB_ID: 193514

PHYSIOL-LEFT-TO-RIGHT

ACTIVATION

Reactome DB_ID: 193426

UniProt:O14734 ACOT8

ACOT8

ACOT8PTE1ACTEIIIFUNCTION Acyl-coenzyme A (acyl-CoA) thioesterases are a group of enzymes that catalyze the hydrolysis of acyl-CoAs to the free fatty acid and coenzyme A (CoASH), providing the potential to regulate intracellular levels of acyl-CoAs, free fatty acids and CoASH (PubMed:9299485, PubMed:9153233, PubMed:15194431). Acyl-coenzyme A thioesterase 8/ACOT8 display no strong substrate specificity with respect to the carboxylic acid moiety of Acyl-CoAs (By similarity). Hydrolyzes medium length (C2 to C20) straight-chain, saturated and unsaturated acyl-CoAS but is inactive towards substrates with longer aliphatic chains (PubMed:9299485, PubMed:9153233). Moreover, it catalyzes the hydrolysis of CoA esters of bile acids, such as choloyl-CoA and chenodeoxycholoyl-CoA and competes with bile acid CoA:amino acid N-acyltransferase (BAAT) (By similarity). ACOT8 is also able to hydrolyze CoA esters of dicarboxylic acids (By similarity). It is involved in the metabolic regulation of peroxisome proliferation (PubMed:15194431).FUNCTION (Microbial infection) May mediate Nef-induced down-regulation of CD4 cell-surface expression (PubMed:9153233).ACTIVITY REGULATION Inhibited by CoASH (IC(50)=10-15 uM). Also inhibited by cysteine-reactive agents.PATHWAY Lipid metabolism; fatty acid metabolism.SUBUNIT Homodimer (By similarity).SUBUNIT (Microbial infection) Interacts with human immunodeficiency virus (HIV-1) Nef (via middle region); this interaction enhances ACOT8 Acyl-CoA thioesterase activity and occurs in a Nef myristoylation-independent manner (PubMed:9299485). According to a second report, the interaction with HIV-1 Nef occurs in a Nef myristoylation-independent manner but does not enhance ACOT8 Acyl-CoA thioesterase activity (PubMed:9153233).TISSUE SPECIFICITY Detected in a T-cell line (at protein level). Ubiquitous (PubMed:9153233, PubMed:9299485).INDUCTION Regulated by peroxisome proliferator (such as Clofibrate), via the peroxisome proliferator-activated receptors (PPARs).SIMILARITY Belongs to the C/M/P thioester hydrolase family.

UniProtO14734

EQUAL

319

EQUAL

GO0003986

GO molecular function

Reactome Database ID Release 75390301Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=390301Reactome Database ID Release 75390304Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=390304ReactomeR-HSA-390304

Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-390304.110092594Pubmed1999Identification of peroxisomal acyl-CoA thioesterases in yeast and humansJones, JMNau, KGeraghty, Michael TErdmann, RGould, Stephen JJ Biol Chem 274:9216-2316756494Pubmed2006Biochemistry of mammalian peroxisomes revisitedWanders, Ronald J AWaterham, HRAnnu Rev Biochem 75:295-332

2.3.1.7

propionyl-CoA + carnitine => propionylcarnitine + CoASH

Peroxisomal carnitineacetyltransferase (CRAT) catalyzes the reaction of propionyl-CoA and carnitine to form propionylcarnitine and CoASH. The active form of the enzyme is a monomer (Bloisi et al. 1990; Wu et al. 2003).

Authored: D'Eustachio, P, 2009-03-16 18:50:14Reviewed: Jassal, Bijay, 2009-02-27Edited: D'Eustachio, P, 2009-03-18 13:33:40

Reactome DB_ID: 390294

Reactome DB_ID: 192314

Reactome DB_ID: 390274

O-propanoylcarnitine [ChEBI:28867]

O-propanoylcarnitine

ChEBI28867

Reactome DB_ID: 193514

PHYSIOL-LEFT-TO-RIGHT

ACTIVATION

Reactome DB_ID: 390293

EQUAL

626

EQUAL

Reactome Database ID Release 75390284Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=390284ReactomeR-HSA-390284

Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-390284.1

Reactome Database ID Release 75389887Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=389887ReactomeR-HSA-389887

Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-389887.3GO0033540

GO biological process