fatty acid oxidation

Etomoxir is a carnitine palmitoyltransferase 1a (CPT-1a) inhibitor that inhibits fatty acid oxidation by inhibiting CPT-1a and inhibits palmitate oxidation in humans, rats, and guinea pigs. Etomoxir has an inhibitory effect on adenine nucleotide translocase and can inhibit macrophage polarization by disrupting CoA homeostasis.

L-Carnitine (L(-)-Carnitine) is an amino acid derivative. L-Carnitine facilitates long-chain fatty acid entry into mitochondria, delivering substrate for oxidation and subsequent energy production. Fatty acids are utilized as an energy substrate in all tissues except the brain.

Gemfibrozil (CI-719) interacts with peroxisome proliferator-activated receptors (PPARalpha) resulting in PPARalpha-mediated stimulation of fatty acid oxidation and an increase in lipoprotein lipase (LPL) synthesis. Gemfibrozil is a fibric acid derivative with hypolipidemic effects. This enhances triglyceride-rich lipoprotein clearance and reduces the expression of apolipoprotein C-III (apoC-III). The reduction in hepatic production of apoC-III result in the subsequent reduction of serum levels of very-low-density-lipoprotein cholesterol (VLDL-C). In addition, gemfibrozil-mediated PPARalpha stimulation of apoA-I and apoA-II expression results in an increase in high-density lipoprotein cholesterol (HDL-C).

NAD+ (β-Nicotinamide Adenine Dinucleotide) is a coenzyme composed of ribosylnicotinamide 5'-diphosphate coupled to adenosine 5'-phosphate by pyrophosphate linkage. It is found widely in nature and is involved in numerous enzymatic reactions in which it serves as an electron carrier by being alternately oxidized (NAD+) and reduced (NADH).

Triheptanoin (IND 106011) is a fatty acid metabolic modulator. It potentially for the treatment of fatty acid oxidation disorders and GLUT1.

CVT-2738 (RS-94287) is a metabolite of Ranolazine. Ranolazine is a partial fatty acid oxidation (pFOX) inhibitor and anti-anginal drug.

Suberic acid (1,8-Octanedioic acid) is present in the urine of patients with fatty acid oxidation disorders. A metabolic breakdown product derived from oleic acid. Elevated levels of this unstaruated dicarboxylic acid are found in individuals with medium-chain acyl-CoA dehydrogenase deficiency (MCAD). Suberic acid is also associated with carnitine-acylcarnitine translocase deficiency, malonyl-Coa decarboxylase deficiency.

Trans-2-butene-1,4-dicarboxylic acid (3-Hexenedioic Acid) is a normal human unsaturated dicarboxylic acid metabolite with increased excretion in patients with Dicarboxylic aciduria caused by fatty acid metabolism disorders The urinary excretion of Trans-2-butene-1,4-dicarboxylic acid is increased in conditions of augmented mobilization of fatty acids or inhibited fatty acid oxidation.

Tetradecylthioacetic acid is a synthetic fatty acid with a sulfur substitution in the β-position. This modification renders TTA unable to undergo complete β-oxidation and increases its biological activity, including activation of peroxisome proliferator activated receptors (PPARs) with preference for PPARα.

P053 is a potent, non-competitive, and selective ceramide synthase 1 (CerS1) inhibitor with an IC50 of 0.5 μM. It acts as an endogenous inhibitor of mitochondrial fatty acid oxidation in muscle and regulates whole-body adiposity[1].

Etomoxir sodium salt ((R)-Etomoxir sodium salt) is a carnitine palmitoyltransferase 1a (CPT-1a) inhibitor that inhibits fatty acid oxidation (FAO). Etomoxir sodium salt has antitumor activity.

N-Isovaleroylglycine (Isovaleroylglycine) is an acyl glycine. Acyl glycines are normally minor metabolites of fatty acids. However, the excretion of certain acyl glycines is increased in several inborn errors of metabolism. In certain cases, the measurement of these metabolites in body fluids can be used to diagnose disorders associated with mitochondrial fatty acid beta-oxidation. Acyl glycines are produced through the action of glycine N-acyltransferase which is an enzyme that catalyzes the chemical reaction: acyl-CoA + glycine < -- > CoA + N-acylglycine. N-Isovaleroylglycine is a byproduct of the catabolism of the amino acid leucine. Accumulation of N-Isovaleroylglycine occurs in Isovaleric Acidemia (IVA).

10,12-Tricosadiynoic acid is a highly selective and orally active inhibitor of acyl-CoA oxidase-1 (ACOX1), which can treat high-fat diet- or obesity-induced metabolic diseases by improving mitochondrial lipid and ROS metabolism.

Palmitoylcarnitine (Palmitoyl DL-carnitine) is a mitochondrial fatty acid oxidation intermediate that acts as a surfactant.

Palmitoylcarnitine chloride (Palmitoyl DL-carnitine chloride) is a mitochondrial fatty acid oxidation intermediate that mediates intralipid cardioprotection.Palmitoylcarnitine chloride eliminates colorectal cancer cell survival by depletion of glutathione. induces cancer cell death and regulates the interaction between protein kinase C βII and its receptor RACK1.

Dodecanoylcarnitine ((-)-Lauroylcarnitine) has been associated with disturbances in fatty acid oxidation, and the use of Dodecanoylcarnitine resulted in an increase in the permeability of salmon calcitonin.

CP-640186 is an isozyme-nonselective Acetyl-CoA carboxylase (ACCase) inhibitor. The IC50s of CP-640186(CP 640186) is 53 nM and 61 nM for rat liver ACC1 and rat skeletal muscle ACC2 respectively.

(R)-Aminocarnitine (Emeriamine) TFA is an inhibitor of fatty acid oxidation, effective in decreasing hyperglycemia and ketosis. This compound is used in research of metabolic diseases.

HDAC11-IN-2 (compound B6) is a highly selective inhibitor of Histone Deacetylase 11 (HDAC11). It demonstrates IC50 values of 51.1 ×10^-3 μM for HDAC11 and 5 μM for HDAC8. HDAC11-IN-2 reduces de novo lipogenesis (DNL) and enhances fatty acid oxidation, which alleviates hepatic lipid accumulation and pathological symptoms in MASLD mice. By inhibiting HDAC11, HDAC11-IN-2 enhances the phosphorylation of AMPKα1 at the Thr172 site, thereby modulating de novo lipogenesis and fatty acid oxidation in the liver.

Trimetazidine, an anti-ischemic (anti-anginal) metabolic agent, could improve myocardial glucose utilization through inhibition of long-chain 3-ketoacyl CoA thiolase activity and results in a reduction in fatty acid oxidation and a stimulation of glucose

C108297 is a glucocorticoid receptor modulator. C108297 prevents both diet-induced obesity and inflammation. C108297 decreased food and fructose intake and increased lipolysis in white adipose tissue (WAT) and free fatty acid levels in plasma, resulting i

(±)11-HETE is one of the six monohydroxy fatty acids produced by the non-enzymatic oxidation of arachidonic acid . The individual R and S isomers of racemic HETEs have been separated and identified using chiral phase HPLC. The racemic HETEs have been quantified as an index of lipid peroxidation using GC/MS.

(±)10-HDHA is an autoxidation product of docosahexaenoic acid (DHA) in vitro.[1][2] It is also produced from incubations of DHA in rat liver, brain, and intestinal microsomes.[3][4][5] (±)10-HDHA is a potential marker of oxidative stress in brain and retina where DHA is an abundant polyunsaturated fatty acid. Reference:[1]. VanRollins, M., and Murphy, R.C. Autooxidation of docosahexaenoic acid: Analysis of ten isomers of hydroxydocosahexaenoate. J. Lipid Res. 25(5), 507-517 (1984).[2]. Reynaud, D., Thickitt, C.P., and Pace-Asciak, C.R. Facile preparation and structural determination of monohydroxy derivatives of docosahexaenoic acid (HDoHE) by α-tocopherol-directed autoxidation. Anal. Biochem. 214(1), 165-170 (1993).[3]. VanRollins, M., Baker, R.C., Sprecher, H., et al. Oxidation of docosahexaenoic acid by rat liver microsomes. J. Biol. Chem. 259(9), 5776-5783 (1984).[4]. Yamane, M., Abe, A., and Yamane, S. High-performance liquid chromatography-thermospray mass spectrometry of epoxy polyunsaturated fatty acids and epoxyhydroxy polyunsaturated fatty acids from an incubation mixture of rat tissue homogenate. J. Chromatogr. 652(2), 123-136 (1994).[5]. Kim, H.Y., Karanian, J.W., Shingu, T., et al. Sterochemical analysis of hydroxylated docosahexaenoates produced by human platelets and rat brain homogenate. Prostaglandins 40(5), 473-490 (1990).

Ajoene is a disulfide that has been found inA. sativumand has diverse biological activities, including antibacterial, anticancer, antiplatelet, and antioxidant properties.1,2,3,4It is active against Gram-positive (MICs = 5-160 µg/ml) and Gram-negative bacteria (MICs = 136-200 µg/ml), as well as yeasts (MICs = 10-20 µg/ml).1Ajoene is cytotoxic to mouse melanoma cells (IC50= 18 µM), as well as human colon, lung, mammary, and pancreatic cancer cells (IC50s = 7-41 µM).2It reduces tumor growth in a B16/BL6 mouse model of melanoma when administered at a dose of 25 mg/kg every other day and decreases the number of lung metastases when administered prior to tumor cell inoculation at doses ranging from 1-25 mg/kg. It inhibits ADP- or collagen-induced platelet aggregation in isolated baboon platelets when used at concentrations ranging from 75 to 150 µg/ml and in platelet-rich plasma isolated from baboons when administered at a dose of 25 mg/kg.3Ajoene (25 mg/kg) prevents thrombus formation on damaged arterial walls in heparinized pigs in anin situmodel of thrombogenesis.5It also reduces high-fat diet-induced hepatic steatosis, histopathological markers of liver damage, thiobarbituric acid reactive substances (TBARS) formation, and protein oxidation in a mouse model of non-alcoholic fatty liver disease (NAFLD).4 1.Naganawa, R., Iwata, N., Ishikawa, K., et al.Inhibition of microbial growth by ajoene, a sulfur-containing compound derived from garlicAppl. Environ. Microbiol.62(11)4238-4242(1996) 2.Taylor, P., Noriega, R., Farah, C., et al.Ajoene inhibits both primary tumor growth and metastasis of B16/BL6 melanoma cells in C57BL/6 miceCancer Lett.239(2)298-304(2006) 3.Teranishi, K., Apitz-Castro, R., Robson, S.C., et al.Inhibition of baboon platelet aggregation in vitro and in vivo by the garlic derivative, ajoeneXenotransplantation10(4)374-379(2003) 4.Han, C.Y., Ki, S.H., Kim, Y.W., et al.Ajoene, a stable garlic by-product, inhibits high fat diet-induced hepatic steatosis and oxidative injury through LKB1-dependent AMPK activationAntioxid. Redox Signal.14(2)187-202(2011) 5.Apitz-Castro, R., Badimon, J.J., and Badimon, L.A garlic derivative, ajoene, inhibits platelet deposition on severely damaged vessel wall in an in vivo porcine experimental modelThromb. Res.75(3)243-249(1994)