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Disorders caused by deficiency of succinate-CoA ligase

  • SSIEM SYMPOSIUM 2007
  • Published:
Journal of Inherited Metabolic Disease

Summary

Succinate-CoA ligase catalyses the reversible conversion of succinyl-CoA and ADP or GDP to succinate and ATP or GTP. It is a mitochondrial matrix enzyme and at least the ADP-forming enzyme is part of the Krebs cycle. The substrate specificity is determined by the β subunit of succinate-CoA ligase, which is encoded by either SUCLA2 or SUCLG2. In patients with severe hypotonia, deafness and Leigh-like syndrome, mutations have been found in SUCLA2. Mutations have also been reported in SUCLG1, which encodes the α subunit found in both enzymes, in patients with severe infantile acidosis and lactic aciduria. Elevated methylmalonate and methylcitrate and severe mtDNA depletion were found in both disorders. The mtDNA depletion may be explained by the interaction of succinate-CoA ligase with nucleoside diphosphate kinase, which is involved in mitochondrial nucleotide metabolism.

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Abbreviations

MMA:

methylmalonate

NDPK:

nucleoside diphosphate kinase

SUCL:

succinate-CoA ligase

A-SUCL:

ADP-forming succinate-CoA ligase

G-SUCL:

GDP-forming succinate-CoA ligase

References

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Authors and Affiliations

  1. Department of Clinical Genetics 4062, National University Hospital Rigshospitalet, Blegdamsvej 9, 2100, Copenhagen, Denmark

    E. Ostergaard

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  1. E. Ostergaard
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Correspondence to E. Ostergaard.

Additional information

Communicating editor: John Walter

Competing interests: None declared

References to electronic databases: SUCLG1, OMIM 611224, Genbank accession number NM_003849. SUCLA2, OMIM 603921, Genbank accession number NM_003850. ADP-forming succinate-CoA ligase, EC 6.2.1.5. GDP-forming succinate-CoA ligase, EC 6.2.1.4. Nucleoside diphosphate kinase, EC 2.7.4.6. MITOP2: http://www.mitop2.de.

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Ostergaard, E. Disorders caused by deficiency of succinate-CoA ligase. J Inherit Metab Dis 31, 226–229 (2008). https://doi.org/10.1007/s10545-008-0828-7

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  • DOI: https://doi.org/10.1007/s10545-008-0828-7

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