ACOT5 Inhibitors
Chemical inhibitors of ACOT5, a key enzyme in fatty acid metabolism, include a diverse group of compounds that interfere with various aspects of lipid synthesis and degradation. Triclosan is one such inhibitor, which can disrupt lipid synthesis pathways and thus interfere with the functionality of ACOT5. By targeting enzymes upstream of ACOT5, such as enoyl-acyl carrier protein reductase, Triclosan reduces the availability of acyl-CoAs, which are necessary substrates for ACOT5's enzymatic activity. Similarly, Orlistat, a lipase inhibitor, limits the breakdown of fats, consequently decreasing the levels of free fatty acids and their acyl-CoA derivatives for ACOT5 to act upon. This results in a reduced capacity for ACOT5 to perform its role in fatty acid metabolism.
Furthermore, Triacsin C and Cerulenin act upstream by inhibiting long-chain acyl-CoA synthetase and fatty acid synthase, respectively. These actions result in a diminished pool of acyl-CoA molecules for ACOT5 to hydrolyze. Perhexiline and Etomoxir, both inhibitors of carnitine palmitoyltransferase 1 (CPT1), alter the mitochondrial uptake and oxidation of fatty acids. This can lead to an accumulation of acyl-CoAs in the cytosol, and while this might suggest an increased substrate availability for ACOT5, it can also result in a feedback inhibition scenario where the enzyme is overwhelmed by the excess acyl-CoAs. In a similar vein, Thiazolidinediones, through their activation of PPAR-gamma, can modulate the cellular concentration of fatty acids and their related coenzyme A derivatives, thereby influencing ACOT5 activity indirectly. GSK2194069 and C75, both inhibitors of fatty acid synthase, reduce the synthesis of fatty acids, leading to a concomitant decrease in acyl-CoA substrates for ACOT5. AICAR, by activating AMP-activated protein kinase, shifts cellular metabolism toward fatty acid oxidation and away from lipogenesis, effectively decreasing the acyl-CoA pool. Lastly, Oxfenicine inhibits carnitine acetyltransferase, which could disrupt the acyl-CoA/CoA balance and potentially impede ACOT5 activity through substrate competition or feedback inhibition mechanisms.
SEE ALSO...
| Product Name | CAS # | Catalog # | QUANTITY | Price | Citations | RATING |
|---|---|---|---|---|---|---|
Triclosan | 3380-34-5 | sc-220326 sc-220326A | 10 g 100 g | $141.00 $408.00 | ||
Triclosan can inhibit ACOT5 by interfering with lipid synthesis pathways. ACOT5, being an acyl-CoA thioesterase, is crucial for the hydrolysis of acyl-CoAs to free fatty acids and CoA, a step important in fatty acid metabolism. Triclosan, known to inhibit enoyl-acyl carrier protein reductase involved in fatty acid synthesis, could reduce the availability of acyl-CoAs, thus indirectly reducing ACOT5 substrate availability and inhibiting its activity. | ||||||
Lipase Inhibitor, THL | 96829-58-2 | sc-203108 | 50 mg | $52.00 | 7 | |
Orlistat, a lipase inhibitor, can indirectly inhibit ACOT5 by reducing the breakdown of fats, which could lower the levels of fatty acids and their corresponding acyl-CoAs, the substrates for ACOT5. This could result in diminished activity of ACOT5 due to the lack of substrate availability. | ||||||
Triacsin C Solution in DMSO | 76896-80-5 | sc-200574 sc-200574A | 100 µg 1 mg | $187.00 $843.00 | 14 | |
Triacsin C inhibits long-chain acyl-CoA synthetase, which is responsible for converting free fatty acids into fatty acyl-CoA substrates for ACOT5. Inhibiting this enzyme would decrease the availability of acyl-CoA substrates for ACOT5, thereby functionally inhibiting ACOT5 activity. | ||||||
Cerulenin (synthetic) | 17397-89-6 | sc-200827 sc-200827A sc-200827B | 5 mg 10 mg 50 mg | $161.00 $312.00 $1210.00 | 9 | |
Cerulenin inhibits fatty acid synthase, leading to a decreased synthesis of fatty acids. As ACOT5 is involved in the hydrolysis of acyl-CoAs, a reduction in fatty acid synthesis would likely lead to a decrease in acyl-CoA levels, thereby indirectly inhibiting ACOT5 by limiting its substrate. | ||||||
(+)-Etomoxir sodium salt | 828934-41-4 | sc-215009 sc-215009A | 5 mg 25 mg | $151.00 $506.00 | 3 | |
Etomoxir inhibits CPT1, similar to Perhexiline. By inhibiting CPT1, etomoxir can decrease fatty acid oxidation, potentially increasing acyl-CoA levels in the cytosol, which could lead to feedback inhibition of ACOT5, as it may be unable to process the excess acyl-CoAs efficiently. | ||||||
Rosiglitazone | 122320-73-4 | sc-202795 sc-202795A sc-202795C sc-202795D sc-202795B | 25 mg 100 mg 500 mg 1 g 5 g | $120.00 $326.00 $634.00 $947.00 $1259.00 | 38 | |
Thiazolidinediones activate PPAR-gamma, a nuclear receptor that regulates fatty acid storage and glucose metabolism. Activation of PPAR-gamma can alter fatty acid metabolism, potentially decreasing the availability of acyl-CoA substrates for ACOT5, and thus indirectly inhibiting the enzyme’s activity. | ||||||
Lonafarnib | 193275-84-2 | sc-482730 sc-482730A | 5 mg 10 mg | $173.00 $234.00 | ||
C75 is a synthetic inhibitor of fatty acid synthase, and by inhibiting fatty acid production, C75 would reduce the substrate availability for ACOT5, thus indirectly inhibiting the enzyme’s activity. | ||||||
AICAR | 2627-69-2 | sc-200659 sc-200659A sc-200659B | 50 mg 250 mg 1 g | $65.00 $280.00 $400.00 | 48 | |
AICAR is an activator of AMP-activated protein kinase (AMPK). When activated, AMPK can enhance fatty acid oxidation and inhibit lipogenesis, which could reduce the cytosolic pool of acyl-CoAs, the substrates for ACOT5, indirectly inhibiting its enzymatic activity. | ||||||