is an acronym for succinate dehydrogenase complex subunit A
The term SDHA can refer to;
- The protein subunit itself.
- The gene that codes for this protein.
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
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:
- SDHA converts succinate to fumarate as part of the Citric Acid Cycle. This reaction also converts FAD to FADH2.
- 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
- Finally the electrons are transferred to the Ubiquinone (Q) pool via the SDHC/SDHD subunits.
Gene that Codes for SDHA
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
mutations (i.e. both copies of the gene are mutated) have been described in Leigh syndrome
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. This would require the improbable event of inactivation of all four alleles to trigger a paraganglioma.