Enzymes
| UniProtKB help_outline | 181 proteins |
| GO Molecular Function help_outline |
|
Reaction participants Show >> << Hide
- Name help_outline H2O Identifier CHEBI:15377 (Beilstein: 3587155; CAS: 7732-18-5) help_outline Charge 0 Formula H2O InChIKeyhelp_outline XLYOFNOQVPJJNP-UHFFFAOYSA-N SMILEShelp_outline [H]O[H] 2D coordinates Mol file for the small molecule Search links Involved in 6,204 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
-
Namehelp_outline
N6-biotinyl-L-lysyl-[protein]
Identifier
RHEA-COMP:10505
Reactive part
help_outline
- Name help_outline N6-biotinyl-L-lysine residue Identifier CHEBI:83144 Charge 0 Formula C16H26N4O3S SMILEShelp_outline *-N[C@@H](CCCCNC(=O)CCCC[C@@H]1SC[C@@H]2NC(=O)N[C@H]12)C(-*)=O 2D coordinates Mol file for the small molecule Search links Involved in 12 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
- Name help_outline NAD+ Identifier CHEBI:57540 (Beilstein: 3868403) help_outline Charge -1 Formula C21H26N7O14P2 InChIKeyhelp_outline BAWFJGJZGIEFAR-NNYOXOHSSA-M SMILEShelp_outline NC(=O)c1ccc[n+](c1)[C@@H]1O[C@H](COP([O-])(=O)OP([O-])(=O)OC[C@H]2O[C@H]([C@H](O)[C@@H]2O)n2cnc3c(N)ncnc23)[C@@H](O)[C@H]1O 2D coordinates Mol file for the small molecule Search links Involved in 1,186 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
- Name help_outline 2''-O-biotinyl-ADP-D-ribose Identifier CHEBI:189573 Charge -2 Formula C25H35N7O16P2S InChIKeyhelp_outline GCWCBBFOEBTFCM-ZRNDBVKMSA-L SMILEShelp_outline O1C(O)[C@H](OC(CCCC[C@@H]2SC[C@]3([C@@]2(NC(N3)=O)[H])[H])=O)[C@H](O)[C@H]1COP(OP(OC[C@@H]4[C@H]([C@H]([C@H](N5C6=NC=NC(=C6N=C5)N)O4)O)O)(=O)[O-])(=O)[O-] 2D coordinates Mol file for the small molecule Search links Involved in 1 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
-
Namehelp_outline
L-lysyl-[protein]
Identifier
RHEA-COMP:9752
Reactive part
help_outline
- Name help_outline L-lysine residue Identifier CHEBI:29969 Charge 1 Formula C6H13N2O SMILEShelp_outline C([C@@H](C(*)=O)N*)CCC[NH3+] 2D coordinates Mol file for the small molecule Search links Involved in 136 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
- Name help_outline nicotinamide Identifier CHEBI:17154 (Beilstein: 383619; CAS: 98-92-0) help_outline Charge 0 Formula C6H6N2O InChIKeyhelp_outline DFPAKSUCGFBDDF-UHFFFAOYSA-N SMILEShelp_outline NC(=O)c1cccnc1 2D coordinates Mol file for the small molecule Search links Involved in 61 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
Cross-references
| RHEA:70479 | RHEA:70480 | RHEA:70481 | RHEA:70482 | |
|---|---|---|---|---|
| Reaction direction help_outline | undefined | left-to-right | right-to-left | bidirectional |
| UniProtKB help_outline |
|
|||
| Gene Ontology help_outline |
Related reactions help_outline
More general form(s) of this reaction
Publications
-
Sirtuin 4 is a lipoamidase regulating pyruvate dehydrogenase complex activity.
Mathias R.A., Greco T.M., Oberstein A., Budayeva H.G., Chakrabarti R., Rowland E.A., Kang Y., Shenk T., Cristea I.M.
Sirtuins (SIRTs) are critical enzymes that govern genome regulation, metabolism, and aging. Despite conserved deacetylase domains, mitochondrial SIRT4 and SIRT5 have little to no deacetylase activity, and a robust catalytic activity for SIRT4 has been elusive. Here, we establish SIRT4 as a cellula ... >> More
Sirtuins (SIRTs) are critical enzymes that govern genome regulation, metabolism, and aging. Despite conserved deacetylase domains, mitochondrial SIRT4 and SIRT5 have little to no deacetylase activity, and a robust catalytic activity for SIRT4 has been elusive. Here, we establish SIRT4 as a cellular lipoamidase that regulates the pyruvate dehydrogenase complex (PDH). Importantly, SIRT4 catalytic efficiency for lipoyl- and biotinyl-lysine modifications is superior to its deacetylation activity. PDH, which converts pyruvate to acetyl-CoA, has been known to be primarily regulated by phosphorylation of its E1 component. We determine that SIRT4 enzymatically hydrolyzes the lipoamide cofactors from the E2 component dihydrolipoyllysine acetyltransferase (DLAT), diminishing PDH activity. We demonstrate SIRT4-mediated regulation of DLAT lipoyl levels and PDH activity in cells and in vivo, in mouse liver. Furthermore, metabolic flux switching via glutamine stimulation induces SIRT4 lipoamidase activity to inhibit PDH, highlighting SIRT4 as a guardian of cellular metabolism. << Less
Cell 159:1615-1625(2014) [PubMed] [EuropePMC]
This publication is cited by 1 other entry.