Enzymes
UniProtKB help_outline | 4 proteins |
Enzyme class help_outline |
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Reaction participants Show >> << Hide
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Namehelp_outline
apo-[propionyl-CoA:carbon-dioxide ligase (ADP-forming)]
Identifier
RHEA-COMP:10511
Reactive part
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- 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 137 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
- Name help_outline biotin Identifier CHEBI:57586 (Beilstein: 10186323) help_outline Charge -1 Formula C10H15N2O3S InChIKeyhelp_outline YBJHBAHKTGYVGT-ZKWXMUAHSA-M SMILEShelp_outline [H][C@]12CS[C@@H](CCCCC([O-])=O)[C@@]1([H])NC(=O)N2 2D coordinates Mol file for the small molecule Search links Involved in 14 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
- Name help_outline ATP Identifier CHEBI:30616 (Beilstein: 3581767) help_outline Charge -4 Formula C10H12N5O13P3 InChIKeyhelp_outline ZKHQWZAMYRWXGA-KQYNXXCUSA-J SMILEShelp_outline Nc1ncnc2n(cnc12)[C@@H]1O[C@H](COP([O-])(=O)OP([O-])(=O)OP([O-])([O-])=O)[C@@H](O)[C@H]1O 2D coordinates Mol file for the small molecule Search links Involved in 1,284 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
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Namehelp_outline
holo-[propionyl-CoA:carbon-dioxide ligase (ADP-forming)]
Identifier
RHEA-COMP:10512
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 AMP Identifier CHEBI:456215 Charge -2 Formula C10H12N5O7P InChIKeyhelp_outline UDMBCSSLTHHNCD-KQYNXXCUSA-L SMILEShelp_outline Nc1ncnc2n(cnc12)[C@@H]1O[C@H](COP([O-])([O-])=O)[C@@H](O)[C@H]1O 2D coordinates Mol file for the small molecule Search links Involved in 512 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
- Name help_outline diphosphate Identifier CHEBI:33019 (Beilstein: 185088) help_outline Charge -3 Formula HO7P2 InChIKeyhelp_outline XPPKVPWEQAFLFU-UHFFFAOYSA-K SMILEShelp_outline OP([O-])(=O)OP([O-])([O-])=O 2D coordinates Mol file for the small molecule Search links Involved in 1,139 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 9,521 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
Cross-references
RHEA:11204 | RHEA:11205 | RHEA:11206 | RHEA:11207 | |
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Reaction direction help_outline | undefined | left-to-right | right-to-left | bidirectional |
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MetaCyc help_outline |
Publications
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Mutations in the holocarboxylase synthetase gene HLCS.
Suzuki Y., Yang X., Aoki Y., Kure S., Matsubara Y.
Holocarboxylase synthetase (HLCS) deficiency is an autosomal recessive disorder. HLCS is an enzyme that catalyzes biotin incorporation into carboxylases and histones. Since the first report of the cDNA sequence, 30 mutations in the HLCS gene have been reported. Mutations occur throughout the entir ... >> More
Holocarboxylase synthetase (HLCS) deficiency is an autosomal recessive disorder. HLCS is an enzyme that catalyzes biotin incorporation into carboxylases and histones. Since the first report of the cDNA sequence, 30 mutations in the HLCS gene have been reported. Mutations occur throughout the entire coding region except exons 6 and 10. The types of mutations are one single amino acid deletion, five single nucleotide insertions/deletions, 22 missense mutations, and two nonsense mutations. The only intronic mutation identified thus far is c.1519+5G>A (also designated IVS10+5G>A), which causes a splice error. Several lines of evidence suggest that c.1519+5G>A is a founder mutation in Scandinavian patients. Prevalence of this mutation is about 10 times higher in the Faroe Islands than in the rest of the world. The mutations p.L237P and c.780delG are predominant only in Japanese patients. These are probably founder mutations in this population. Mutations p.R508W and p.V550M are identified in several ethic groups and accompanied with various haplotypes, suggesting that these are recurrent mutations. There is a good relationship between clinical biotin responsiveness and the residual activity of HLCS. A combination of a null mutation and a point mutation that shows less than a few percent of the normal activity results in neonatal onset. Patients who have mutant HLCS with higher residual activity develop symptom after the neonatal period and show a good clinical response to biotin therapy. << Less
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THE ENZYMATIC SYNTHESIS OF PROPIONYL COENZYME A HOLOCARBOXYLASE FROM D-BIOTINYL 5'-ADENYLATE AND THE APOCARBOXYLASE.
SIEGEL L., FOOTE J.L., COON M.J.
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Relationship between kinetic properties of mutant enzyme and biochemical and clinical responsiveness to biotin in holocarboxylase synthetase deficiency.
Sakamoto O., Suzuki Y., Li X., Aoki Y., Hiratsuka M., Suormala T., Baumgartner E.R., Gibson K.M., Narisawa K.
Holocarboxylase synthetase (HCS) deficiency is a metabolic disorder that causes a biotin-responsive multiple carboxylase deficiency. We analyzed the kinetic properties of seven mutant HCS proteins. Two of these enzymes harbored mutations within the putative biotin-binding region of HCS and showed ... >> More
Holocarboxylase synthetase (HCS) deficiency is a metabolic disorder that causes a biotin-responsive multiple carboxylase deficiency. We analyzed the kinetic properties of seven mutant HCS proteins. Two of these enzymes harbored mutations within the putative biotin-binding region of HCS and showed elevated Km values for biotin compared with that of the wild-type form (Km mutant; Gly581Ser: 45 times, delThr610: 3 times). The remaining five mutations (Arg183Pro, Leu216Arg, Leu237Pro, Val333Glu, and Val363Asp) were located outside the biotin-binding region. The enzymes containing these mutations showed normal or low Km values for biotin (non-Km mutant). Symptoms of patients who have the non-Km, mutants, as well as those of patients who have the Km, mutants, responded to biotin therapy. This is probably because the Km value for biotin of normal HCS is higher than the physiologic concentration of biotin in human cells. The Vmax values of all mutant HCS proteins were considerably decreased, but to a variable degree. The responsiveness to biotin supplementation of propionyl-CoA carboxylase activity in cultured cells bearing the mutations correlated well with the degree of reduction in the Vmax of HCS. Patients who have mutant HCS proteins with lower Vmax showed poorer clinical and biochemical responses to biotin therapy. These observations suggest that the reduction of Vmax is an essential factor for pathophysiology and prognosis of HCS deficiency under treatment with large amounts of biotin. The determination of HCS genotype can be valuable for characterizing the clinical phenotype in HCS deficient patients. << Less