SDHD
Encyclopedia
Succinate dehydrogenase [ubiquinone] cytochrome b small subunit, mitochondrial (CybS), also known as succinate dehydrogenase complex subunit D (SDHD), is a protein
that in humans is encoded by the SDHD gene
.
SDHD, which stands for succinate dehydrogenase complex subunit D, is one of the two transmembrane subunits of the four-subunit succinate dehydrogenase protein complex that resides in the inner mitochondrial membrane. It also refers to the gene
that codes for this protein. The other transmembrane subunit is SDHC. SDHD/SDHC are connected to the SDHB
electron transfer subunit. SDHB in turn transfers electrons from the SDHA
subunit to the SDHC/SDHD dimer
.
Succinate dehydrogenase is an important enzyme
in both the citric acid cycle
and the electron transfer chain
The SDHD gene is located on chromosome 11, at locus
11q23. Names previously used for SDHD were PGL and PGL1.
can cause familial paraganglioma
.
Germline mutations in SDHD were first linked to hereditary paraganglioma in 2000. Since then, it has been shown that mutations in SDHB and to a lesser degree SDHC can cause paranglioma as well familial pheochromocytoma
. Notably, the tumor spectrum is different for the different mutations. SDHB mutations often lead to metastatic disease that is extra-adrenal, while SDHD mutation related tumors are more typically benign, originating in the head and neck.
The exact mechanism for tumorigenesis is not determined, but it is suspected that malfunction of the SDH complex can cause a hypoxic
response in the cell that leads to tumor formation. People living at higher altitudes (for example, the Andes mountains) are known to have an increased rate of benign paraganglioma, with the rate of disease increasing with the altitude of the population.
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
that in humans is encoded by the SDHD gene
Gene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...
.
SDHD, which stands for succinate dehydrogenase complex subunit D, is one of the two transmembrane subunits of the four-subunit succinate dehydrogenase protein complex that resides in the inner mitochondrial membrane. It also refers to the gene
Gene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...
that codes for this protein. The other transmembrane subunit is SDHC. SDHD/SDHC are connected to the SDHB
SDHB
Succinate dehydrogenase [ubiquinone] iron-sulfur subunit, mitochondrial also known as iron-sulfur subunit of complex II is a protein that in humans is encoded by the SDHB gene....
electron transfer subunit. SDHB in turn transfers electrons from the SDHA
SDHA
Succinate dehydrogenase complex, subunit A, flavoprotein variant is a protein that in humans is encoded by the SDHA gene.The succinate dehydrogenase protein complex catalyzes the oxidation of succinate . The SDHA subunit is connected to the SDHB subunit on the hydrophilic, catalytic end of the...
subunit to the SDHC/SDHD dimer
Protein dimer
In biochemistry, a dimer is a macromolecular complex formed by two, usually non-covalently bound, macromolecules like proteins or nucleic acids...
.
Succinate dehydrogenase is an important enzyme
Enzyme
Enzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical reactions in a biological cell need enzymes in order to occur at rates...
in both the citric acid cycle
Citric acid cycle
The citric acid cycle — also known as the tricarboxylic acid cycle , the Krebs cycle, or the Szent-Györgyi-Krebs cycle — is a series of chemical reactions which is used by all aerobic living organisms to generate energy through the oxidization of acetate derived from carbohydrates, fats and...
and the electron transfer chain
The SDHD gene is located on chromosome 11, at locus
Locus (genetics)
In the fields of genetics and genetic computation, a locus is the specific location of a gene or DNA sequence on a chromosome. A variant of the DNA sequence at a given locus is called an allele. The ordered list of loci known for a particular genome is called a genetic map...
11q23. Names previously used for SDHD were PGL and PGL1.
Role in disease
Mutations in the SDHD geneGene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...
can cause familial paraganglioma
Paraganglioma
A paraganglioma is a rare neuroendocrine neoplasm that may develop at various body sites . About 97% are benign and cured by surgical removal; the remaining 3% are malignant because they are able to produce distant metastases...
.
Germline mutations in SDHD were first linked to hereditary paraganglioma in 2000. Since then, it has been shown that mutations in SDHB and to a lesser degree SDHC can cause paranglioma as well familial pheochromocytoma
Pheochromocytoma
A pheochromocytoma or phaeochromocytoma is a neuroendocrine tumor of the medulla of the adrenal glands , or extra-adrenal chromaffin tissue that failed to involute after birth and secretes excessive amounts of catecholamines, usually noradrenaline , and adrenaline to a lesser extent...
. Notably, the tumor spectrum is different for the different mutations. SDHB mutations often lead to metastatic disease that is extra-adrenal, while SDHD mutation related tumors are more typically benign, originating in the head and neck.
The exact mechanism for tumorigenesis is not determined, but it is suspected that malfunction of the SDH complex can cause a hypoxic
Hypoxia (medical)
Hypoxia, or hypoxiation, is a pathological condition in which the body as a whole or a region of the body is deprived of adequate oxygen supply. Variations in arterial oxygen concentrations can be part of the normal physiology, for example, during strenuous physical exercise...
response in the cell that leads to tumor formation. People living at higher altitudes (for example, the Andes mountains) are known to have an increased rate of benign paraganglioma, with the rate of disease increasing with the altitude of the population.