Rabbit anti-Human FH polyclonal antibody

Fumarate hydratase (FH) is an enzyme in the tricarboxylic acid (TCA) cycle, biallelic loss-of-function mutations of which are associated with hereditary leiomyomatosis and renal cell cancer. However, how FH defect modulates intracellular metabolic fluxes in human cells has remained unclear. This study aimed to reveal metabolic flux alterations induced by reduced FH activity. We applied C-13 metabolic flux analysis (C-13-MFA) to an established cell line with diminished FH activity (FHdim) and parental HEK293 cells. FHdim cells showed reduced pyruvate import flux into mitochondria and subsequent TCA cycle fluxes. Interestingly, the diminished FH activity decreased FH flux only by about 20%, suggesting a very low need for FH to maintain the oxidative TCA cycle. Cellular ATP production from the TCA cycle was dominantly suppressed compared with that from glycolysis in FHdim cells. Consistently, FHdim cells exhibited higher glucose dependence for ATP production and higher resistance to an ATP synthase inhibitor. In summary, using FHdim cells we demonstrated that FH defect led to suppressed pyruvate import into mitochondria, followed by downregulated TCA cycle activity and altered ATP production pathway balance from the TCA cycle to glycolysis. We confirmed that C-13-MFA can provide direct and quantitative information on metabolic alterations induced by FH defect.

Purpose The study examined the association between mastoid pneumatization (MP) volume and the existence of foramen Huschke (FH). Methods Cone beam computed tomography (CBCT) images of 1117 patients (2234 mastoid regions) were analyzed. The prevalence of FH was calculated. The association of MP volume calculated in 83 patients (48 women, 35 men) with sex, side, and the existence of FH analyzed.Ttest and Pearson's Chi-square test were used for statistical analyses. Results FH was observed in 223 (20%) patients. FH was unilateral in 141 (63.7%) patients (74 left-sided, 68 right-sided) and bilateral in 81 (36.3%) patients. Six patients with FH had herniation into the external auditory canal. MP volume was significantly greater in females (p = 0.016). Additionally, MP volume was significantly greater in patients having FH (p = 0.009). Conclusion It is possible to speculate that the volume of MP, which is in close neighborhood with the external auditory canal, somehow affects the existence of FH located in the tympanic segment.