Acyl-CoA dehydrogenase
From Proteopedia
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== Function == | == Function == | ||
| - | '''Acyl-CoA dehydrogenase''' (ACDH) catalyzes the introduction of a double bond between C2 and C3 of the thio-ester CoA substrate. This is the first reaction in fatty acid metabolism which produces acetyl-CoA. FAD is the cofactor of ACDH activity. ACDH is classified according to the length of its substrates as short- (SCAD), medium- (MCAD), very- and very long-chain (VLCAD) ACDH. MCAD can bind a broad range of chain length acyl-CoA substrates.<ref>PMID:7601336</ref> | + | '''Acyl-CoA dehydrogenase''' (ACDH) catalyzes the introduction of a double bond between C2 and C3 of the thio-ester CoA substrate. This is the first reaction in fatty acid metabolism which produces acetyl-CoA. FAD is the cofactor of ACDH activity. ACDH is classified according to the length of its substrates as short- (SCAD), medium- (MCAD), very- and very long-chain (VLCAD) ACDH. MCAD can bind a broad range of chain length acyl-CoA substrates.<ref>PMID:7601336</ref> See also [[Beta oxidation]] and [[Glutaryl-CoA dehydrogenase]]. |
| + | *'''Glutaryl-CoA dehydrogenase''' is required for the metabolism of Lys, Trp and hydroxyLys. | ||
| + | *'''Isovaleryl-CoA dehydrogenase''' catalyzes the conversion of isovaleryl-CoA to 3-methylcrotonyl-CoA<ref>PMID:9665741</ref>. | ||
| + | *'''3-hydroxyacyl-CoA dehydrogenase''' oxidates straight chain 3-hydroxyacyl-CoA<ref>PMID:16176262</ref>. | ||
== Disease == | == Disease == | ||
| - | Impairment of the activity of ACDH causes a variety of diseases associated with lack of fatty acid metabolism. MCAD mutations are associated with Sudden Infant Death. | + | Impairment of the activity of ACDH causes a variety of diseases associated with lack of fatty acid metabolism. MCAD mutations are associated with Sudden Infant Death and with Medium-chain Acyl-CoA Dehydrogenase Deficiency (MCADD)<ref>PMID:32809672</ref>. For details see [[Investigating the Mechanisms of Active Site Mutations to the 1T9G WT MCAD Protein to Better Understand Medium Chain Acyl-CoA Dehydrogenase Deficiency (MCADD)]]. SCAD deficiency is a recessive disorder of fatty acid β-oxidation. |
== Structural highlights == | == Structural highlights == | ||
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SCAD is a homodimer with a single FAD binding site. <scene name='49/491924/Cv/12'>MCAD is a homotetramer</scene> with 4 FAD binding sites in the subunits interface and 4 binding sites for acyl-CoA substrate within each monomer. | SCAD is a homodimer with a single FAD binding site. <scene name='49/491924/Cv/12'>MCAD is a homotetramer</scene> with 4 FAD binding sites in the subunits interface and 4 binding sites for acyl-CoA substrate within each monomer. | ||
*One of the <scene name='49/491924/Cv/9'>FAD binding sites</scene> in homotetramer of rat ACDH. Water molecules are shown as red spheres. | *One of the <scene name='49/491924/Cv/9'>FAD binding sites</scene> in homotetramer of rat ACDH. Water molecules are shown as red spheres. | ||
| - | *One of the <scene name='49/491924/Cv/11'>CoA binding sites</scene> in homotetramer of rat ACDH.<ref>PMID:11812788</ref> | + | *One of the <scene name='49/491924/Cv/11'>CoA binding sites</scene> in homotetramer of rat ACDH.<ref>PMID:11812788</ref> |
==3D structures of acyl-CoA dehydrogenase== | ==3D structures of acyl-CoA dehydrogenase== | ||
[[Acyl-CoA dehydrogenase 3D structures]] | [[Acyl-CoA dehydrogenase 3D structures]] | ||
</StructureSection> | </StructureSection> | ||
| - | ==3D structures of acyl-CoA dehydrogenase== | ||
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| - | Updated on {{REVISIONDAY2}}-{{MONTHNAME|{{REVISIONMONTH}}}}-{{REVISIONYEAR}} | ||
| - | {{#tree:id=OrganizedByTopic|openlevels=0| | ||
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| - | *Short chain ACDH | ||
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| - | **[[1jqi]] - SCAD + acetoacetyl-CoA + FAD – rat<BR /> | ||
| - | **[[2dvl]], [[2z1q]] - TtSCAD + FAD – ''Thermus thermophilus''<BR /> | ||
| - | **[[2jif]], [[2vig]] - hSCAD + CoA persulfide + FAD – human<br /> | ||
| - | **[[5ol2]] – ACDH + FAD + CoA persulfide + electron transfer flavoprotein – ''Clostridium difficile''<br /> | ||
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| - | *Medium chain ACDH | ||
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| - | **[[1ws9]], [[2cx9]] - TtMCAD <BR /> | ||
| - | **[[3mdd]] – pMCAD + FAD – pig<BR /> | ||
| - | **[[1egd]], [[1ege]], [[4p13]] - hMCAD (mutant) + FAD<BR /> | ||
| - | **[[1ukw]], [[2d29]] - TtMCAD + FAD<BR /> | ||
| - | **[[1egc]] - hMCAD (mutant) + octanoyl-CoA + FAD<BR /> | ||
| - | **[[3mde]] - pMCAD + octanoyl-CoA + FAD<BR /> | ||
| - | **[[1udy]] - pMCAD + thiaoctanoyl-CoA + FAD<BR /> | ||
| - | **[[1t9g]] - hMCAD + electron transfer flavoprotein + AMP + FAD<BR /> | ||
| - | **[[2a1t]] - hMCAD + electron transfer flavoprotein (mutant) + AMP + FAD<BR /> | ||
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| - | *Very long chain ACDH | ||
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| - | **[[2uxw]] - hVLCAD + tetradecanoyl CoA + FAD<BR /> | ||
| - | **[[3b96]] - hVLCAD + trans-δ2-palmitenoyl CoA + FAD<BR /> | ||
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| - | *Unspecified length ACDH | ||
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| - | **[[2oku]] – ACDH C terminal – ''Porphyromonas gingivalis''<BR /> | ||
| - | **[[2pg0]] - ACDH + FAD – ''Geobacillus kaustophilus''<BR /> | ||
| - | **[[2wbi]] – hACDH 11 + FAD<BR /> | ||
| - | **[[3nf4]], [[3pfd]] – ACHD + FAD – ''Mycobacterium thermoresistibile''<BR /> | ||
| - | **[[3oib]], [[4iv6]] - ACHD + FAD – ''Mycobacterium smegmatis''<br /> | ||
| - | **[[4x28]] - ACHD + FAD – ''Mycobacterium tuberculosis''<br /> | ||
| - | **[[4m9a]] – ACDH + FAD – ''Burkholderia thailandensis''<br /> | ||
| - | **[[3owa]] - ACDH + FAD – ''Bacillus anthracis''<br /> | ||
| - | **[[4rm7]] – ShACDH – ''Slackia heliotrinireducens''<br /> | ||
| - | **[[4w9u]] – ACDH – ''Brucella abortus''<br /> | ||
| - | **[[5ez3]] – ACDH + FAD – ''Brucella melitensis''<br /> | ||
| - | **[[4y9l]] – CeACDH + FAD – ''Caenorhabditis elegans''<br /> | ||
| - | **[[4y9j]] – CeACDH + FAD + CoA-11<br /> | ||
| - | **[[5af7]] – AmACDH + FAD – ''Advenella mimigardefordensis''<br /> | ||
| - | **[[5ahs]] – AmACDH + FAD + succinyl-CoA<br /> | ||
| - | **[[5lnx]] – ACDH + FAD – ''Bacillus subtilis''<br /> | ||
| - | **[[6es9]] – ACDH + FAD + CoA – ''Paracoccus denitrificans''<br /> | ||
| - | **[[4y9l]] – CeACDH + FAD – ''Caenorhabditis elegans''<br /> | ||
| - | **[[4y9j]] – CeACDH + FAD + undecanoyl-CoA <br /> | ||
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| - | *Butyryl-CoA dehydrogenase | ||
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| - | **[[4u83]] – ShBCDH <br /> | ||
| - | **[[1buc]] – BCDH + acetoacetyl-CoA + FAD – ''Megasphaera elsdenii''<br /> | ||
| - | **[[1rx0]] – hiso-BCDH + methacrylyl-CoA + FAD <br /> | ||
| - | **[[6cy8]], [[6cxt]] – BCDH + alpha/beta hydrolase fold protein + FAD – ''Marinomonas mediterranea''<br /> | ||
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| - | }} | ||
== References == | == References == | ||
<references/> | <references/> | ||
[[Category:Topic Page]] | [[Category:Topic Page]] | ||
Current revision
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References
- ↑ Thorpe C, Kim JJ. Structure and mechanism of action of the acyl-CoA dehydrogenases. FASEB J. 1995 Jun;9(9):718-25. PMID:7601336
- ↑ Mohsen AW, Anderson BD, Volchenboum SL, Battaile KP, Tiffany K, Roberts D, Kim JJ, Vockley J. Characterization of molecular defects in isovaleryl-CoA dehydrogenase in patients with isovaleric acidemia. Biochemistry. 1998 Jul 14;37(28):10325-35. PMID:9665741 doi:10.1021/bi973096r
- ↑ Yang SY, He XY, Schulz H. 3-Hydroxyacyl-CoA dehydrogenase and short chain 3-hydroxyacyl-CoA dehydrogenase in human health and disease. FEBS J. 2005 Oct;272(19):4874-83. PMID:16176262 doi:10.1111/j.1742-4658.2005.04911.x
- ↑ Ibrahim SA, Temtem T. Medium-Chain Acyl-CoA Dehydrogenase Deficiency. PMID:32809672
- ↑ Battaile KP, Molin-Case J, Paschke R, Wang M, Bennett D, Vockley J, Kim JJ. Crystal structure of rat short chain acyl-CoA dehydrogenase complexed with acetoacetyl-CoA: comparison with other acyl-CoA dehydrogenases. J Biol Chem. 2002 Apr 5;277(14):12200-7. Epub 2002 Jan 25. PMID:11812788 doi:10.1074/jbc.M111296200
