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Mitochondrial and peroxisomal disorders
Published in Steve Hannigan, Inherited Metabolic Diseases: A Guide to 100 Conditions, 2018
Fumarase deficiency is a rare disorder of the Kreb’s cycle (also known as the citric acid cycle), a metabolic pathway that is central to the breakdown of carbohydrates, fats and proteins to carbon dioxide and water in order to generate energy. Individuals afected by this disorder develop postnatal neurological problems. Patients who have a more severe form of fumarase deiciency usually develop respiratory diiculties, and this results in their life expectancy not extending beyond early childhood, whereas patients who are less severely afected develop non-progressive brain problems and survive into adolescence or adulthood.
Coupling of oxidative stress responses to tricarboxylic acid cycle and prostaglandin E2 alterations in Caenorhabditis elegans under extremely low-frequency electromagnetic field
Published in International Journal of Radiation Biology, 2018
Yongyan Sun, Zhenhua Shi, Yahong Wang, Chao Tang, Yanyan Liao, Chuanjun Yang, Peng Cai
Decreased fumarase expression, both in transcription and translation level in ELF-EMF exposed worms were identified in this study (Figure 1). Fumarase depression can affect hydrolysis of fumarate to malate and result in accumulation of fumarate which is indicated in our previous results (Shi et al. 2015). In recent researches, the fumarase has been regarded as a tumor suppressor gene whose heterozygous mutations predispose to hereditary leiomyomatosis and renal cell cancer (Lorenzato et al. 2008; Wang et al. 2016). Similar inhibitory regulation of fumarase has been reported to cause Mycobacterium tuberculosis hypersusceptible to oxidative stress (Ruecker et al. 2017). Induced oxidative stress by ELF-EMF exposure has been demonstrated in numerous organisms, including in human cells (Garip and Akan 2010) and rats (Bułdak et al. 2012), etc. Similar results of ROS elevation and depressed T-AOC were demonstrated in the following results of this study. Fumarate accumulation and fumarase deficiency can act as a response to oxidative stress induced by ELF-EMF exposure.
Fumarate hydratase as a therapeutic target in renal cancer
Published in Expert Opinion on Therapeutic Targets, 2020
Priyanka Kancherla, Michael Daneshvar, Rebecca A. Sager, Mehdi Mollapour, Gennady Bratslavsky
HLRCC was first described as a familial renal cancer syndrome in 2001 [20]. Genetic linkage analyses identified FH to be the responsible gene [21]. Located on the long arm of chromosome 1 at the 1q42.3-q43 locus, FH encodes fumarate hydratase, a citric acid cycle enzyme. In the case of HLRCC, the disease demonstrates autosomal dominant inheritance with loss of heterozygosity resulting in the phenotypic expression of the disease, suggesting the role of FH as a tumor suppressor gene. Biallelic germline mutation of FH, on the other hand, results in a neurologically devastating and ultimately fatal condition known as fumarase deficiency [22].