fumarate hydratase Inhibitors
Fumarate hydratase inhibitors constitute a diverse class of compounds that exert regulatory control over the enzymatic activity of fumarate hydratase (FH) within the tricarboxylic acid (TCA) cycle. One prominent group includes substrate analogs such as dimethyl fumarate, malonate, succinyl phosphonate, citraconic acid, and sodium fluoroacetate, which directly interfere with FH activity by competitively binding to its active site. These inhibitors disrupt the catalytic conversion of fumarate to malate, resulting in the accumulation of fumarate and perturbation of cellular metabolism.
Another subgroup, represented by compounds like 2-methoxyestradiol, methoxyacetic acid, and alpha-ketoglutaric acid, employs indirect mechanisms to modulate FH expression and activity. These chemicals influence signaling pathways or cellular processes, such as the HIF-1α pathway, cellular redox balance, and TCA cycle flux, ultimately leading to altered FH levels. Additionally, tropolone and methylene blue showcase unique mechanisms by directly interacting with the active site metal ions and influencing cellular redox balance, respectively, underscoring the diverse strategies employed by fumarate hydratase inhibitors. Understanding the intricate interplay between these inhibitors and cellular processes provides valuable insights into the regulatory networks governing fumarate hydratase and its role in cellular metabolism. The specific and targeted actions of these inhibitors emphasize the importance of precise chemical interactions in modulating enzyme function, contributing to the broader understanding of metabolic regulation within cells.
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| Product Name | CAS # | Catalog # | QUANTITY | Price | Citations | RATING |
|---|---|---|---|---|---|---|
Dimethyl fumarate | 624-49-7 | sc-239774 | 25 g | $27.00 | 6 | |
Dimethyl fumarate is a small molecule that directly inhibits fumarate hydratase (FH). It achieves this by forming adducts with the active site cysteine residues of FH, leading to covalent modification and subsequent inhibition of FH enzymatic activity. The direct interaction with the active site disrupts the catalytic conversion of fumarate to malate, effectively impairing the function of FH in the tricarboxylic acid (TCA) cycle. | ||||||
2-Methoxyestradiol | 362-07-2 | sc-201371 sc-201371A | 10 mg 50 mg | $70.00 $282.00 | 6 | |
2-Methoxyestradiol acts as an indirect inhibitor of fumarate hydratase by modulating the hypoxia-inducible factor 1-alpha (HIF-1α) pathway. This compound inhibits HIF-1α, a key regulator of cellular response to hypoxia, by promoting its degradation. As a downstream consequence, the reduced HIF-1α levels lead to diminished expression of fumarate hydratase. | ||||||
Iclaprim | 192314-93-5 | sc-215166 | 25 mg | $10000.00 | ||
Iclaprim, an antibiotic, indirectly influences fumarate hydratase by targeting bacterial dihydrofolate reductase (DHFR), an enzyme crucial for folate metabolism. Inhibition of bacterial DHFR disrupts folate synthesis, impacting the availability of one-carbon units for purine and pyrimidine biosynthesis. This disruption extends to eukaryotic cells sharing similar metabolic pathways, indirectly affecting FH expression and activity. | ||||||
Tropolone | 533-75-5 | sc-253808 sc-253808A | 1 g 5 g | $32.00 $109.00 | ||
Tropolone functions as a direct inhibitor of fumarate hydratase by chelating the active site iron ions essential for enzyme activity. Through its ability to coordinate with the catalytic iron ions, tropolone disrupts the enzyme's metal-dependent catalysis, inhibiting the conversion of fumarate to malate. | ||||||
α-Ketoglutaric Acid | 328-50-7 | sc-208504 sc-208504A sc-208504B sc-208504C sc-208504D sc-208504E sc-208504F | 25 g 100 g 250 g 500 g 1 kg 5 kg 16 kg | $32.00 $42.00 $62.00 $108.00 $184.00 $724.00 $2050.00 | 2 | |
Alpha-ketoglutaric acid serves as an indirect inhibitor of fumarate hydratase by influencing the metabolic flux through the tricarboxylic acid (TCA) cycle. As an intermediate in the TCA cycle, alpha-ketoglutaric acid participates in cellular energy metabolism. Alterations in its levels can impact the overall flux through the TCA cycle, indirectly influencing fumarate hydratase activity. | ||||||
Citraconic acid | 498-23-7 | sc-357316 sc-357316A | 25 g 50 g | $77.00 $135.00 | ||
Citraconic acid acts as a direct inhibitor of fumarate hydratase by forming a covalent adduct with the enzyme's active site cysteine residues. This covalent modification disrupts the catalytic activity of fumarate hydratase, preventing the conversion of fumarate to malate. | ||||||
Methylene blue | 61-73-4 | sc-215381B sc-215381 sc-215381A | 25 g 100 g 500 g | $42.00 $102.00 $322.00 | 3 | |
Methylene Blue acts as an indirect inhibitor of fumarate hydratase by influencing cellular redox balance. As a redox-active compound, methylene blue participates in cellular electron transfer reactions. Its interactions with cellular redox systems impact the cellular redox state, indirectly affecting fumarate hydratase expression and activity. | ||||||