Reaction participants Show >> << Hide
- Name help_outline (3R)-3-hydroxy-4-oxobutanoate Identifier CHEBI:138809 Charge -1 Formula C4H5O4 InChIKeyhelp_outline QWHDXIUUXWGQME-GSVOUGTGSA-M SMILEShelp_outline [O-]C(C[C@H](C([H])=O)O)=O 2D coordinates Mol file for the small molecule Search links Involved in 4 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
- Name help_outline NADP+ Identifier CHEBI:58349 Charge -3 Formula C21H25N7O17P3 InChIKeyhelp_outline XJLXINKUBYWONI-NNYOXOHSSA-K 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](OP([O-])([O-])=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 1,335 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
- Name help_outline H2O Identifier CHEBI:15377 (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 6,485 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
- Name help_outline (R)-malate Identifier CHEBI:15588 Charge -2 Formula C4H4O5 InChIKeyhelp_outline BJEPYKJPYRNKOW-UWTATZPHSA-L SMILEShelp_outline O[C@H](CC([O-])=O)C([O-])=O 2D coordinates Mol file for the small molecule Search links Involved in 9 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
- Name help_outline NADPH Identifier CHEBI:57783 (Beilstein: 10411862) help_outline Charge -4 Formula C21H26N7O17P3 InChIKeyhelp_outline ACFIXJIJDZMPPO-NNYOXOHSSA-J SMILEShelp_outline NC(=O)C1=CN(C=CC1)[C@@H]1O[C@H](COP([O-])(=O)OP([O-])(=O)OC[C@H]2O[C@H]([C@H](OP([O-])([O-])=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 1,329 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
- Name help_outline H+ Identifier CHEBI:15378 Charge 1 Formula H InChIKeyhelp_outline GPRLSGONYQIRFK-UHFFFAOYSA-N SMILEShelp_outline [H+] 2D coordinates Mol file for the small molecule Search links Involved in 9,932 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
Cross-references
| RHEA:81423 | RHEA:81424 | RHEA:81425 | RHEA:81426 | |
|---|---|---|---|---|
| Reaction direction help_outline | undefined | left-to-right | right-to-left | bidirectional |
| UniProtKB help_outline |
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Related reactions help_outline
More general form(s) of this reaction
Publications
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Biochemical and structural elucidation of the L-carnitine degradation pathway of the human pathogen <i>Acinetobacter baumannii</i>.
Piskol F., Lukat P., Kaufhold L., Heger A., Blankenfeldt W., Jahn D., Moser J.
<i>Acinetobacter baumannii</i> is an opportunistic human pathogen which can use host-derived L-carnitine as sole carbon and energy source. Recently, an L-carnitine transporter (Aci1347) and a specific monooxygense (CntA/CntB) for the intracellular cleavage of L-carnitine have been characterized. S ... >> More
<i>Acinetobacter baumannii</i> is an opportunistic human pathogen which can use host-derived L-carnitine as sole carbon and energy source. Recently, an L-carnitine transporter (Aci1347) and a specific monooxygense (CntA/CntB) for the intracellular cleavage of L-carnitine have been characterized. Subsequent conversion of the resulting malic semialdehyde into the central metabolite L-malate was hypothesized. Alternatively, L-carnitine degradation via D-malate with subsequent oxidation into pyruvate was proposed. Here we describe the <i>in vitro</i> and <i>in vivo</i> reconstitution of the entire pathway, starting from the as yet uncharacterized gene products of the carnitine degradation gene operon. Using recombinantly purified enzymes, enantiomer-specific formation of D-malate by the NAD(P)<sup>+</sup>-dependent malic semialdehyde dehydrogenase (MSA-DH) is demonstrated. The solved X-ray crystal structure of tetrameric MSA-DH reveals the key catalytic residues Cys<sup>290</sup> and Glu<sup>256</sup>, accessible through opposing substrate and cofactor funnels. Specific substrate binding is enabled by Arg<sup>166</sup>, Arg<sup>284</sup> and Ser<sup>447</sup> while dual cofactor specificity for NAD<sup>+</sup> and NADP<sup>+</sup> is mediated by Asn<sup>184</sup>. The subsequent conversion of the unusual D-malate reaction product by an uncharacterized NAD<sup>+</sup>-dependent malate dehydrogenase (MDH) is shown. Tetrameric MDH is a β-decarboxylating dehydrogenase that synthesizes pyruvate. MDH experiments with alternative substrates showed a high degree of substrate specificity. Finally, the entire <i>A. baumannni</i> pathway was heterologously reconstituted, allowing <i>E. coli</i> to grow on L-carnitine as a carbon and energy source. Overall, the metabolic conversion of L-carnitine via malic semialdehyde and D-malate into pyruvate, CO<sub>2</sub> and trimethylamine was demonstrated. Trimethylamine is also an important gut microbiota-dependent metabolite that is associated with an increased risk of cardiovascular disease. The pathway reconstitution experiments allowed us to assess the TMA forming capacity of gut microbes which is related to human cardiovascular health. << Less
Front Microbiol 15:1446595-1446595(2024) [PubMed] [EuropePMC]
This publication is cited by 4 other entries.