fatty acid metabolism

Coenzyme A 是所有活细胞中必需的辅助因子，由泛酸，三磷酸腺苷和半胱氨酸合成的。Coenzyme A 与过氧化物酶 5 共价结合导致其过氧化物酶活性完全抑制，通过 DTT 还原能够逆转。Coenzyme A 及其硫酯衍生物是主要分解代谢，合成代谢途径和基因表达调控的关键参与者。

L-Carnitine (L(-)-Carnitine) 是一种人内源性分子，在人体内以蛋氨酸和赖氨酸为底物进行生物合成，并参与脂肪酸代谢。L-Carnitine 将长链脂肪酰辅酶A 转运到线粒体。L-Carnitine 能够改善许多先天性代谢错误的代谢失衡。

Thiamine hydrochloride (Vitamin B1) 是一种必需的微量营养素，是许多中枢代谢酶的辅因子。

Trimetazidine dihydrochloride (Vastarel F) 是细胞保护性抗缺血剂，也用作缺血性心脏病或心绞痛的血管扩张剂，具有抗氧化，抗炎，抗伤害和胃保护作用。它可通过抑制脂肪酸代谢提高心肌葡萄糖利用率。

Biotin (Vitamin H) 属于天然产物，是一种 B 族维生素，具有水溶性。Biotin 参与脂肪酸产生、脂肪和氨基酸代谢以及细胞生长。Biotin 常被用于生物素标记。

L-Carnitine hydrochloride ((R)-Carnitine hydrochloride) 是一种高极性的双离子小分子，是线粒体 β-氧化的重要辅因子。L-Carnitine hydrochloride 促进长链脂酰辅酶 A 转运至线粒体以进行 β-氧化降解，辅助细胞能量代谢。L-Carnitine hydrochloride 还具有抗氧化活性，可缓解多种先天性代谢异常引起的代谢失衡，是代谢研究中的重要工具化合物。

(rac)-Isoleucine 是Isoleucine的外消旋混合物，包含L-isoleucine、L-alloisoleucine、D-isoleucine和D-alloisoleucine。L-Isoleucine作为支链氨基酸参与氮供给、葡萄糖代谢、脂肪酸代谢及免疫功能调节。L-Alloisoleucine由L-Isoleucine经转氨作用生成。

2,2-Dihydroxyacetic acid (Formylformic acid) 是乙醛酸循环的中间体，使某些生物体能够将脂肪酸转化为碳水化合物。2,2-Dihydroxyacetic acid 被发现与原发性高草酸尿有关，这是一种先天性代谢错误。作为一种醛，乙醛酸酯也具有高活性，可以修饰蛋白质形成晚期糖基化产物(AGEs)。

Acetoacetic acid lithium salt (Lithium 3-Oxobutyrate) 是内源性代谢产物的一种。

Erucic acid (13(Z)-Docosenoic Acid) 是单不饱和脂肪酸，分离自萝卜的种子。Erucic acid 可以容易地穿过血脑屏障，使大脑中长链脂肪酸的积累正常化。Erucic acid 能够改善认知障碍并有效预防痴呆。

3-Hydroxybutyric acid (Butanoic acid) 是人内源性代谢物，一种内源性的组蛋白去乙酰化酶 (HDAC) 抑制剂，对 HDAC3、HDAC4、HDAC1 的 IC50为2.4 mM、4.5 mM、5.3 mM。3-Hydroxybutyric acid有能量代谢、神经保护、抗炎作用、改善胰岛素抵抗作用。

Trans-​2-​butene-​1,​4-​dicarboxylic acid (3-Hexenedioic Acid) 是内源性代谢产物的一种。

D-Pantothenic acid (vitamin B5) 是必需的微量营养素，是辅酶 A 的前体，在很多生物过程中发挥关键作用，如调节碳水化合物，脂质，蛋白和核酸代谢。

Perhexiline maleate 是一种口服活性的 CPT1和 CPT2抑制剂，可降低脂肪酸的代谢。Perhexiline maleate 对大鼠心脏和肝脏CPT 1的IC50值分别为77 和 148 μM。

RP 54275 是一种天然存在的脂肪酸衍生物，一种新的降胆固醇化合物。它可以激活过氧化物酶体增殖物激活受体γ（PPARγ）途径，该途径参与脂质代谢、炎症和细胞分化的调节。

Nicodicosapent is a fatty acid niacin conjugate. It is also an inhibitor of the sterol regulatory element-binding protein (SREBP). The sterol regulatory element-binding protein (SREBP) is a key regulator of cholesterol metabolism proteins such as PCSK9, H

Deprodone 是一种活性化合物。它通过与耐甲氧西林金黄色葡萄球菌 (MRSA) 的水解酶和转移酶蛋白相互作用，抑制细菌细胞壁合成等关键过程。Deprodone 被应用于MRSA感染、炎症性皮肤病、肠道疾病和脂肪酸代谢紊乱的研究。

Trimetazidine是一种无关血流动力学的抗心绞痛剂，能够选择性地抑制mitochondrial enzyme 3-ketoacyl coenzyme A thiolase（LC 3-KAT）从而防止游离脂肪酸的β-氧化，IC50 值为 75 nM。Trimetazidine通过改变心脏代谢防止缺血再灌注损伤，具有抗氧化和抗缺血伤害的作用。

Lauroyl-coenzyme A can function as an acyl group carrier, acetyl-CoA. It can be used as an intermediate in lipid metabolism and is involved in lipid biosynthesis and fatty acid transport.

Cytochrome P450 metabolism of polyunsaturated fatty acids produces numerous bioactive epoxide regioisomers. (±)10(11)-EpDPA is a docosahexaenoic acid epoxygenase metabolite, derived via epoxidation of the 10,11-double bond of DHA. It has been detected in rat brain and spinal cord, as well as human serum, and acts as a substrate for soluble epoxide hydrolase with a Km value of 5.1 μM. (±)10(11)-EpDPA and other epoxy metabolites of DHA are reported to demonstrate antihyperalgesic activity in inflammatory and neuropathic pain models and to potently inhibit angiogenesis and tumor growth in in vitro assays.

Cytochrome P450 metabolism of polyunsaturated fatty acids produces numerous bioactive epoxide regioisomers. (±)13(14)-EpDPA is a docosahexaenoic acid epoxygenase metabolite, derived via epoxidation of the 13,14-double bond of DHA. It has been detected in rat brain and spinal cord and is a preferred substrate for soluble epoxide hydrolase with a Km value of 3.2 μM. (±)13(14)-EpDPA demonstrates antihyperalgesic activity in inflammatory and neuropathic pain models. (±)13(14)-EpDPA and other epoxy metabolites of DHA are also reported to potently inhibit angiogenesis and tumor growth in in vitro assays.

Octanoic acid-13C is intended for use as an internal standard for the quantification of octanoic acid by GC- or LC-MS. Octanoic acid is a medium-chain saturated fatty acid. It has been found in Teleme cheeses made from goat, ovine, or bovine milk.1 Octanoic acid is active against the bacteria S. mutans, S. gordonii, F. nucleatum, and P. gingivalis (IC80s = <125, <125, 1,403, and 2,294 μM, respectively).2 Levels of octanoic acid are increased in the plasma of patients with medium-chain acyl-CoA dehydrogenase (MCAD) deficiency, an inborn error of fatty acid metabolism characterized by hypoketotic hypoglycemia, medium-chain dicarboxylic aciduria, and intolerance to fasting.3,4 |1. Mallatou, H., Pappa, E., and Massouras, T. Changes in free fatty acids during ripening of Teleme cheese made with ewes', goats', cows' or a mixture of ewes' and goats' milk. Int. Dairy J. 13(1-3), 211-219 (2003).|2. Hyang, C.B., Alimova, Y., Myers, T.M., et al. Short- and medium-chain fatty acids exhibit antimicrobial activity for oral microorganisms. Arch. Oral Biol. 56(7), 650-654 (2011).|3. Onkenhout, W., Venizelos, V., van der Poel, P.F.H., et al. Identification and quantification of intermediates of unsaturated fatty acid metabolism in plasma of patients with fatty acid oxidation disorders. Clin. Chem. 41(10), 1467-1474 (1995).|4. Rinaldo, P., O'Shea, J.J., Coates, P.M., et al. Medium-chain acyl-CoA dehydrogenase deficiency. Diagnosis by stable-isotope dilution measurement of urinary n-hexanoylglycine and 3-phenylpropionylglycine. N. Engl. J. Med. 319(20), 1308-1313 (1988).

Peroxisome proliferator-activated receptors (PPARs) α, δ, γ are ligand-activated nuclear transcription factors involved in the regulation of energy homeostasis as well as insulin sensitivity and glucose metabolism. Pharmacologies of PPARδ receptor agonists, though relatively obscure, have recently been reported to elevate high-density lipoprotein (HDL) cholesterol and lower plasma triglyceride (TG) levels in obese insulin resistant rhesus monkeys. CAY10592 is a full PPARδ agonist (EC50 = 30 nM) in a fatty acid oxidation assay of rat L6 muscle cells with desirable oral pharmacokinetic properties. In a transactivation assay using human PPAR receptors, CAY10592 acts as a selective partial PPARδ agonist (EC50 = 53 nM) with no effect on PPARα or PPARγ activity up to 30 μM. Chronic treatment of high fat fed ApoB100/CETP-transgenic mice with CAY10592 at a dose of 20 mg/kg increases HDL levels, decreases LDL and TG levels, and improves insulin sensitivity.

ZLY032 is a dual agonist of free fatty acid receptor 1 (FFAR1/GPR40; EC50= 68 nM in a FLIPR assay) and peroxisome proliferator-activated receptor δ (PPARδ; EC50= 102 nM in a reporter assay).1It is selective for FFAR1 and PPARδ over PPARα and PPARγ (EC50s = >10 μM for both). ZLY032 (40 mg/kg, twice per day) reduces blood glucose levels in an oral glucose tolerance test and decreases plasma total cholesterol and triglyceride levels in theob/obmouse model of metabolic disease.2It reduces hepatic steatosis and plasma alanine transaminase (ALT) and aspartate aminotransferase (AST) levels in a mouse model of non-alcoholic steatohepatitis (NASH) induced by a methionine and choline-deficient diet at the same dose. 1.Li, Z., Chen, Y., Zhou, Z., et al.Discovery of first-in-class thiazole-based dual FFA1/PPARδ agonists as potential anti-diabetic agentsEur. J. Med. Chem.164352-365(2019) 2.Li, Z., Zhou, Z., Hu, L., et al.ZLY032, the first-in-class dual FFA1/PPARδ agonist, improves glucolipid metabolism and alleviates hepatic fibrosisPharmacol Res.159105035(2020)