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 fattyacid oxidation and a stimulation of glucose
Palmitic acid-13C (C1, C2, C3, and C4 labeled) is intended for use as an internal standard for the quantification of palmitic acid by GC- or LC-MS. Palmitic acid is a common 16-carbon saturated fat that represents 10-20% of human dietary fat intake and comprises approximately 25 and 65% of human total plasma lipids and saturated fattyacids, respectively.1,2Acylation of palmitic acid to proteins facilitates anchoring of membrane-bound proteins to the lipid bilayer and trafficking of intracellular proteins, promotes protein-vesicle interactions, and regulates various G protein-coupled receptor functions.1Red blood cell palmitic acid levels are increased in patients with metabolic syndrome compared to patients without metabolic syndrome and are also increased in the plasma of patients with type 2 diabetes compared to individuals without diabetes.3,4 1.Fatima, S., Hu, X., Gong, R.-H., et al.Palmitic acid is an intracellular signaling molecule involved in disease developmentCell. Mol. Life Sci.76(13)2547-2557(2019) 2.Santos, M.J., López-Jurado, M., Llopis, J., et al.Influence of dietary supplementation with fish oil on plasma fattyacid composition in coronary heart disease patientsAnn. Nutr. Metab.39(1)52-62(1995) 3.Yi, L.-Z., He, J., Liang, Y.-Z., et al.Plasma fattyacidmetabolic profiling and biomarkers of type 2 diabetes mellitus based on GC/MS and PLS-LDAFEBS Lett.580(30)6837-6845(2006) 4.Kabagambe, E.K., Tsai, M.Y., Hopkins, P.N., et al.Erythrocyte fattyacid composition and the metabolic syndrome: A National Heart, Lung, and Blood Institute GOLDN studyClin. Chem.54(1)154-162(2008)
ZLY032 is a dual agonist of free fattyacid 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)
10-PAHSA is a newly identified endogenous lipid that belongs to a collection of branched fattyacid esters of hydroxy fattyacids (FAHFAs). It is a FAHFA in which palmitic acid is esterified to 10-hydroxy stearic acid. Among the FAHFA family members, PAHSAs are the most abundant in the adipose tissue of glucose tolerant AG4OX mice, which overexpress the Glut4 glucose transporter specifically in adipose tissue. As other FAHFAs improve glucose tolerance, stimulate insulin secretion, and have anti-inflammatory effects, 10-PAHSA may be a bioactive lipid with roles in metabolic syndrome and inflammation.
Methylmalonyl coenzyme A (methylmalonyl-CoA) is an intermediate in multiple metabolic pathways in bacteria and eukaryotes.1,2,3It is an intermediate in carbon assimilation in certain bacteria and carbon fixation in plants.1,2Methylmalonyl-CoA is converted to succinyl-CoA by methylmalonyl-CoA mutase with vitamin B12as a coenzyme.3A deficiency in vitamin B12leads to a build-up of methylmalonyl-CoA.4 1.Anthony, C.How half a century of research was required to understand bacterial growth on C1 and C2 compounds; the story of the serine cycle and the ethylmalonyl-CoA pathwaySci. Prog.94(Pt 2)109-137(2011) 2.Tabita, F.R.The hydroxypropionate pathway of CO2 fixation: Fait accompliProc. Natl. Acad. Sci. U.S.A.106(50)21015-21016(2009) 3.Medicine, I.o.Vitamin B12Dietary reference intakes for thiamin, riboflavin, niacin, vitamin B6, folate, vitamin B12, pantothenic acid, biotin, and choline306-356(1998) 4.Cardinale, G.J., Carty, T.J., and Abeles, R.H.Effect of methylmalonyl coenzyme A, a metabolite which accumulates in vitamin B12 deficiency, on fattyacid synthesisJ. Biol. Chem.245(15)3771-3775(1970)
Octanoyl coenzyme A (octanoyl-CoA) is a medium-chain acyl CoA and a metabolic intermediate in mitochondrial fattyacid β-oxidation. Levels of octanoyl-CoA are increased in the liver of patients with Reye's syndrome and β-oxidation of octanoyl-CoA by medium-chain acyl CoA dehydrogenase (MCADH) is decreased in patients with MCADH deficiency (MCD). Octanoyl-CoA inhibits citrate synthase and glutamate dehydrogenase.
Carnitine facilitates the transport of fattyacids into the mitochondria to be used in fattyacid metabolism. It does so by accepting acyl groups from fattyacids complexed with coenzyme A, which yields esterified carnitine or acylcarnitines that enable the transport of fatty acyl groups into the inner mitochondrial matrix. β-Oxidation of fattyacids in mitochondria is inhibited by uncoupling conditions, thus changes in circulating levels of various acylcarnitines have been used to identify alterations in metabolic state.[1] [2] Arachidonoyl-L-carnitine formed from carnitine conjugated to arachidonic acid .
Phospholipase A2 (PLA2) catalyzes the hydrolysis of phospholipids at the sn-2 position leading to the production of lysophospholipids and free fattyacids. Calcium-dependent cytosolic PLA2 (cPLA2α) is a 85 kDa enzyme that plays a key role in the arachidonic cascade and the inflammatory response associated with this metabolic pathway. CAY10502 is a potent inhibitor of calcium-dependent cytosolic PLA2α (cPLA2α) with an IC50 value of 4.3 nM for the purified enzyme from human platelets. It inhibits arachidonic acid mobilization from A23187-stimulated or TPA-stimulated human platelets with IC50 values of 570 and 0.9 nM, respectively.
The endocannabinoids, 2-arachidonoyl glycerol (2-AG) and arachidonoyl ethanolamide (AEA), are biologically active lipids that regulate diverse neurological and metabolic functions by activating the cannabinoid receptors, central cannabinoid (CB1) and peripheral cannabinoid (CB2). Monoacylglycerol lipase (MAGL) and fattyacid amide hydrolase (FAAH) hydrolyze 2-AG and AEA, respectively, thus terminating their biological function. IDFP is an organophosphorus compound that dually inhibits MAGL and FAAH with IC50 values of 0.8 and 3 nM, respectively. At 10 mg/kg, IDFP elevates brain levels of 2-AG and AEA more than 10-fold, and decreases levels of arachidonic acid by a similar magnitude.
Galactosylcerebrosides are glycosphingolipids that contain a galactose attached to a ceramide acylated with a hydroxy or non-hydroxy fattyacid. They are metabolic precursors to sulfatides , found primarily in nerve tissues, and are the main glycosphingolipids in the central nervous system. Galactosylcerebrosides are involved in a multitude of cellular processes including cell agglutination, cellular signaling in glycosynapses, cellular development, and activation of T cells. They accumulate in globoid cells in the brain of patients with Krabbe disease, a disorder characterized by a deficiency in galactosylcerebrosidase activity. This product is a mixture of isolated bovine hydroxy galactosylcerebrosides.
Galactosylcerebrosides are glycosphingolipids that contain a galactose attached to a ceramide acylated with a hydroxy or non-hydroxy fattyacid. They are metabolic precursors to sulfatides , found primarily in nerve tissues, and are the main glycosphingolipids in the central nervous system. Galactosylcerebrosides are involved in a multitude of cellular processes including cell agglutination, cellular signaling in glycosynapses, cellular development, and activation of T cells. They accumulate in globoid cells in the brain of patients with Krabbe disease, a disorder characterized by a deficiency in galactosylcerebrosidase activity. This product is a mixture of isolated bovine non-hydroxy galactosylcerebrosides.
Certain chronic neurologic disorders, such as Parkinson's disease, are caused by an insufficiency of the neurotransmitter dopamine secondary to the degeneration of substantia nigra dopaminergic neurons. N-(α-Linolenoyl) tyrosine (NALT) is a simple α-amide conjugate between the ω-3 essential fattyacid α-linolenate and the amino acid tyrosine. α-Linolenate is an important precursor to docosahexaenoic acid (DHA), a prominent brain polyunsaturated fattyacid, while tyrosine is the metabolic precursor for neuronal dopamine synthesis. NALT was prepared as a method for enhancing central nervous system (CNS) dopamine content by facilitated transport of the tyrosine precursor across the blood-brain barrier. In experimental rat models of dopamine insufficiency, NALT increased CNS dopamine levels and exhibited an activity profile consistent with an anti-Parkinson's therapeutic agent.