SDHA

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Succinate dehydrogenase complex, subunit A, flavoprotein (Fp)
SuccDeh.svg
PDB rendering based on 2h89.
Available structures
PDB Ortholog search: PDBe, RCSB
Identifiers
Symbols SDHA ; CMD1GG; FP; PGL5; SDH1; SDH2; SDHF
External IDs OMIM600857 MGI1914195 HomoloGene3073 ChEMBL: 5758 GeneCards: SDHA Gene
EC number 1.3.5.1
Orthologs
Species Human Mouse
Entrez 6389 66945
Ensembl ENSG00000073578 ENSMUSG00000021577
UniProt P31040 Q8K2B3
RefSeq (mRNA) NM_004168 NM_023281
RefSeq (protein) NP_004159 NP_075770
Location (UCSC) Chr 5:
0.22 – 0.26 Mb
Chr 13:
74.32 – 74.35 Mb
PubMed search [1] [2]

Succinate dehydrogenase complex, subunit A, flavoprotein variant is a protein that in humans is encoded by the SDHA gene.[1][2]

The succinate dehydrogenase (SDH) protein complex catalyzes the oxidation of succinate (succinate + ubiquinone => fumarate + ubiquinol). The SDHA subunit is connected to the SDHB subunit on the hydrophilic, catalytic end of the complex, and weighs 72.7 kDA. Electrons removed from succinate transfer to SDHA, transfer across SDHB to the SDHC/SDHD subunits on the hydrophobic end of the complex anchored in the mitochondrial membrane.

Function of the SDHA Protein[edit]

The SDH complex is located on the inner membrane of the mitochondria and participates in both the Citric Acid Cycle and Respiratory chain.

SDHA acts as an intermediate in the basic SDH enzyme action:

  1. SDHA converts succinate to fumarate as part of the Citric Acid Cycle. This reaction also converts FAD to FADH2.
  2. Electrons from the FADH2 are transferred to the SDHB subunit iron clusters [2Fe-2S],[4Fe-4S],[3Fe-4S]. This function is part of the Respiratory chain
  3. Finally the electrons are transferred to the Ubiquinone (Q) pool via the SDHC/SDHD subunits.

Gene that Codes for SDHA[edit]

The gene that codes for the SDHA protein is nuclear, even though the protein is located in the inner membrane of the mitochondria. The location of the gene in humans is on the fifth chromosome at p15. The gene is partitioned in 15 exons. The expressed protein has 664 amino acids.

Role in Disease[edit]

Bi-allelic mutations (i.e. both copies of the gene are mutated) have been described in Leigh syndrome.

Mutations in the SDHA subunit have a distinct pathology from mutations in the SDHB/SDHC/SDHD subunits; it is the only subunit to never have shown tumor suppressor behaviour. Heterozygous carriers of an SDHA mutation do not develop paragangliomas as has been seen for mutations in the other subunits. This appears to be due to the expression of two similar SDHA genes (Types I and II) in the paraganglia system.[3] This would require the improbable event of inactivation of all four alleles to trigger a paraganglioma.

Interactive pathway map[edit]

Click on genes, proteins and metabolites below to link to respective articles. [§ 1]

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TCA Cycle edit
  1. ^ The interactive pathway map can be edited at WikiPathways: "TCACycle_WP78". 

References[edit]

  1. ^ "Entrez Gene: succinate dehydrogenase complex". 
  2. ^ Hirawake H, Wang H, Kuramochi T, Kojima S, Kita K (July 1994). "Human complex II (succinate-ubiquinone oxidoreductase): cDNA cloning of the flavoprotein (Fp) subunit of liver mitochondria". J. Biochem. 116 (1): 221–7. PMID 7798181. 
  3. ^ Brière JJ, Favier J, Bénit P, El Ghouzzi V, Lorenzato A, Rabier D, Di Renzo MF, Gimenez-Roqueplo AP, Rustin P (November 2005). "Mitochondrial succinate is instrumental for HIF1alpha nuclear translocation in SDHA-mutant fibroblasts under normoxic conditions". Hum. Mol. Genet. 14 (21): 3263–9. doi:10.1093/hmg/ddi359. PMID 16195397. 

Further reading[edit]