Enzymes
| UniProtKB help_outline | 1,672 proteins |
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- Name help_outline maleate Identifier CHEBI:30780 Charge -2 Formula C4H2O4 InChIKeyhelp_outline VZCYOOQTPOCHFL-UPHRSURJSA-L SMILEShelp_outline [O-]C(=O)\C=C/C([O-])=O 2D coordinates Mol file for the small molecule Search links Involved in 7 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
- Name help_outline citrate Identifier CHEBI:16947 (CAS: 126-44-3) help_outline Charge -3 Formula C6H5O7 InChIKeyhelp_outline KRKNYBCHXYNGOX-UHFFFAOYSA-K SMILEShelp_outline OC(CC([O-])=O)(CC([O-])=O)C([O-])=O 2D coordinates Mol file for the small molecule Search links Involved in 31 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
Cross-references
| RHEA:72491 | RHEA:72492 | RHEA:72493 | RHEA:72494 | |
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| Reaction direction help_outline | undefined | left-to-right | right-to-left | bidirectional |
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Publications
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Pathogenic mutations of the human mitochondrial citrate carrier SLC25A1 lead to impaired citrate export required for lipid, dolichol, ubiquinone and sterol synthesis.
Majd H., King M.S., Smith A.C., Kunji E.R.S.
Missense mutations of the human mitochondrial citrate carrier, encoded by the SLC25A1 gene, lead to an autosomal recessive neurometabolic disorder characterised by neonatal-onset encephalopathy with severe muscular weakness, intractable seizures, respiratory distress, and lack of psychomotor devel ... >> More
Missense mutations of the human mitochondrial citrate carrier, encoded by the SLC25A1 gene, lead to an autosomal recessive neurometabolic disorder characterised by neonatal-onset encephalopathy with severe muscular weakness, intractable seizures, respiratory distress, and lack of psychomotor development, often resulting in early death. Here, we have measured the effect of all twelve known pathogenic mutations on the transport activity. The results show that nine mutations abolish transport of citrate completely, whereas the other three reduce the transport rate by >70%, indicating that impaired citrate transport is the most likely primary cause of the disease. Some mutations may be detrimental to the structure of the carrier, whereas others may impair key functional elements, such as the substrate binding site and the salt bridge network on the matrix side of the carrier. To understand the consequences of impaired citrate transport on metabolism, the substrate specificity was also determined, showing that the human citrate carrier predominantly transports citrate, isocitrate, cis-aconitate, phosphoenolpyruvate and malate. Although D-2- and L-2 hydroxyglutaric aciduria is a metabolic hallmark of the disease, it is unlikely that the citrate carrier plays a significant role in the removal of hydroxyglutarate from the cytosol for oxidation to oxoglutarate in the mitochondrial matrix. In contrast, computer simulations of central metabolism predict that the export of citrate from the mitochondrion cannot be fully compensated by other pathways, restricting the cytosolic production of acetyl-CoA that is required for the synthesis of lipids, sterols, dolichols and ubiquinone, which in turn explains the severe disease phenotypes. << Less
Biochim. Biophys. Acta 1859:1-7(2018) [PubMed] [EuropePMC]
This publication is cited by 6 other entries.