EC Number   |
General Information |
Reference |
|---|
    1.3.5.1 | evolution |
enzyme QFR is a member of the complex II superfamily and is composed of FrdABCD subunits |
763250 |
| 1.3.5.1 | evolution |
one menaquinone molecule is bound near heme bL in the hydrophobic subunit C. This location of the menaquinone-binding site differs from the menaquinol-binding cavity proposed previously for QFR from Wolinella succinogenes. The observed bound menaquinone might serve as an additional redox cofactor to mediate the proton-coupled electron transport across the membrane |
-, 763727 |
| 1.3.5.1 | evolution |
quinol:fumarate reductase (QFR) is a member of the respiratory complex II superfamily |
763400 |
| 1.3.5.1 | evolution |
the enzyme as respiratory complex II belongs to the succinate:quinone oxidoreductases superfamily that comprises succinate:quinone reductases and quinol:fumarate reductases |
-, 724421 |
| 1.3.5.1 | evolution |
the SDH function is regulated through distinct molecular pathways in different species |
762781 |
| 1.3.5.1 | evolution |
the SDH function is regulated through distinct molecular pathways in different species. SDH has evolved to have extra roles in certain microorganisms and immune cells to meet the energy demands of the cells |
762781 |
| 1.3.5.1 | malfunction |
impaired function of SDH results in deleterious disorders from cancer to neurodegeneration. Defective SDH leads to tumorigenesis, where accumulated succinate promotes HIF-1 stabilization. In humans, another regulatory mechanism through alternative splicing of SDHC transcript is reported in which a shorter isoform of SDHC (DELTA5 lacking exon 5) is produced which lacks heme binding region and therefore has no function. This results in significant downregulation of SDH complex. This variant of SDHC may, therefore, act as a dominant-negative inhibitor of full-length SDHC. DELAT5 may have a role in the pathogenesis of tumorigenesis associated with the malfunction of SDH. A posttranscriptional regulation has been described in late stages of lung cancer in which miR-210 (a microRNA) is overexpressed in normoxia. miR-210 targets SDHD and other transcripts of complex I and II such as NDUAF4 eventually leading to mitochondrial dysfunction and cell death. miR-210-dependent targeting of SDHD transcript activates HIF-1 and in agreement with earlier findings links loss-of-function SDH mutations to HIF-1 stabilization. A mutation in K547 of SDHA (which is typically desuccinylated by SIRT5) renders SDHA unable to interact with SDH5 and thereby made SDH inactive. Furthermore, SIRT5 promotes clear cell renal cell carcinoma (ccRCC) proliferation through inactivation of SDH and switching metabolism to aerobic glycolysis |
762781 |
| 1.3.5.1 | malfunction |
the frequency of polymorphisms of SDHs, hypoxia-inducible factor type 1 and angiotensin converting enzyme genes is compared between 40 subjects with intolerance to high altitude and a low hypoxic ventilatory response at exercise and 41 subjects without intolerance to high altitude and a high hypoxic ventilatory. No significant association between low or high hypoxic ventilatory response and the allele frequencies for nine single nucleotide polymorphisms in the SDHD and SDHB genes, the ACE insertion/deletion polymorphism and four single nucleotide polymorphisms in the hypoxia-inducible factor type 1 a gene is found. No clear association is found between gene variants involved in oxygen sensing and chemoresponsiveness, although some mutations in the SDHB and SDHD genes deserve further investigations in a larger population |
697362 |
| 1.3.5.1 | malfunction |
the presentation of three synchronous extra-adrenal abdominal paragangliomas in an adolescent boy who carries a germline mutation in the SDHB gene are reported. Loss of heterozygosity of this allele is demonstrated by direct sequencing of DNA from two of his tumors, confirming loss of tumor suppressor function in the pathogenesis of these paragangliomas |
697078 |
| 1.3.5.1 | malfunction |
the succinate:ubiquinone oxidoreductase activity of the mitochondrial respiratory complex II is specifically impaired by reactive oxygen species without affecting the second enzymatic activity of this complex as a succinate dehydrogenase. The different pro-apoptotic agents responsible for complex II inhibition lead to mitochondrial matrix acidification. Complex II contributes to apoptosis induction only when the SQR activity is inhibited while the SDH activity is still fully functioning,creating an uncoupling phenomenon at the complex II level. The association of an active SDH activity with an inhibited SQR function is not possible, rendering complex II incapable of apoptosis induction and promoting tumourigenesis |
724698 |
