FIH-1 Activators
Factor inhibiting HIF-1 (FIH-1) is an essential enzyme in cellular oxygen sensing mechanisms, functioning as an asparagine hydroxylase that regulates the activity of hypoxia-inducible factor 1α (HIF-1α) under normoxic conditions. By hydroxylating an asparagine residue in HIF-1α, FIH-1 disrupts the interaction of HIF-1α with transcriptional coactivators such as p300/CBP, thereby inhibiting the transcriptional activity of HIF-1α. This hydroxylation reaction is crucial for the suppression of the hypoxic response under normoxic conditions, ensuring that genes involved in angiogenesis, erythropoiesis, and metabolic adaptation to low oxygen levels are not unnecessarily expressed. FIH-1 thus serves as a key regulator of the cellular response to oxygen availability, maintaining cellular homeostasis by hindering the activation of hypoxia-responsive genes under conditions where oxygen is sufficient.
The activation of FIH-1 is closely tied to the availability of its substrates and cofactors, as well as to the cellular oxygen concentration. Under normoxic conditions, FIH-1 is fully active, utilizing molecular oxygen, 2-oxoglutarate, and iron (Fe2+) as cofactors to hydroxylate HIF-1α. This enzymatic activity is directly influenced by the concentration of oxygen; oxygen acts as a substrate for the hydroxylation reaction, enabling FIH-1 to function as an oxygen sensor within the cell. Additionally, the availability of 2-oxoglutarate and the iron status of the cell can modulate the activity of FIH-1, with sufficient levels of these cofactors being essential for its enzymatic function. Furthermore, the post-translational modification of FIH-1, including phosphorylation, can impact its stability and interaction with other proteins, enhancing its ability to regulate HIF-1α activity in response to changing intracellular and extracellular cues. Through these mechanisms, FIH-1 is activated in response to normoxia, playing a critical role in the cellular adaptation to oxygen availability by ensuring the precise regulation of the hypoxic response.
SEE ALSO...
| Product Name | CAS # | Catalog # | QUANTITY | Price | Citations | RATING |
|---|---|---|---|---|---|---|
Ferrous Sulfate (Iron II Sulfate) Heptahydrate | 7782-63-0 | sc-211505 sc-211505A | 250 g 500 g | $73.00 $109.00 | ||
Ferrous sulfate provides essential iron for the TCA cycle and acts as a cofactor for FIH-1. Adequate iron levels promote FIH-1 function, leading to the hydroxylation and degradation of HIF-1α under normoxic conditions. | ||||||
Iron(III) chloride | 7705-08-0 | sc-215192 sc-215192A sc-215192B | 10 g 100 g 500 g | $41.00 $46.00 $87.00 | ||
Ferric chloride is another source of iron that can serve as a cofactor for FIH-1. By providing iron, ferric chloride indirectly supports FIH-1's enzymatic activity, promoting the hydroxylation and subsequent degradation of HIF-1α under normoxic conditions. | ||||||
N-[(4-Hydroxy-1-methyl-7-phenoxy-3-isoquinolinyl)carbonyl]glycine-d3 | 808118-40-3 unlabeled | sc-488006 | 10 mg | $12000.00 | ||
N-[(4-Hydroxy-1-methyl-7-phenoxy-3-isoquinolinyl)carbonyl]glycine-d3 inhibits prolyl hydroxylase enzymes (EGLNs) in the HIF pathway. By inhibiting EGLNs, roxadustat indirectly activates FIH-1, enhancing its availability to hydroxylate HIF-1α and promote its degradation under normoxic conditions. | ||||||
Vitamin K1 | 84-80-0 | sc-280189 sc-280189A | 1 g 5 g | $81.00 $166.00 | ||
Vitamin K1 can influence FIH-1 activity through post-translational modification. Adequate levels of vitamin K1 enhance FIH-1 function, indirectly promoting the hydroxylation of HIF-1α and its degradation under normoxic conditions. | ||||||
Citric Acid, Anhydrous | 77-92-9 | sc-211113 sc-211113A sc-211113B sc-211113C sc-211113D | 500 g 1 kg 5 kg 10 kg 25 kg | $50.00 $110.00 $145.00 $248.00 $598.00 | 1 | |
Citrate is a TCA cycle activator, resulting in the production of α-ketoglutarate (α-KG), a cofactor for FIH-1. Increased citrate levels indirectly activate FIH-1 by enhancing α-KG availability, supporting FIH-1 function, and promoting HIF-1α degradation. | ||||||