Pirinixic acid
From Wikipedia, the free encyclopedia
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| ECHA InfoCard | 100.150.489 |
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| Formula | C14H14ClN3O2S |
| Molar mass | 323.80 g·mol−1 |
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Pirinixic acid is a peroxisome proliferator-activated receptor alpha (PPARα) agonist that is under experimental investigation for prevention of severe cardiac dysfunction, cardiomyopathy and heart failure as a result of lipid accumulation within cardiac myocytes.[1] Treatment is primarily aimed at individuals with an adipose triglyceride lipase (ATGL) enzyme deficiency or mutation[1] because of the essential PPAR protein interactions with free fatty acid monomers derived from the ATGL catalyzed lipid oxidation reaction.[1] It was discovered as WY-14,643 in 1974.[2]
Adipose triglyceride lipase (ATGL), an enzyme that catalyzes the rate limiting hydrolysis step of triglycerides[3] in the triacylglycerol lipolysis cascade, is expressed predominantly in adipose tissue, but is also found in lesser amounts within cardiac and skeletal muscle.[3] Its function is to initiate the breakdown of intracellular triglycerides into fatty acid monomers.[1] Individuals deficient in the ATGL enzyme are at higher risk for cardiac dysfunction and premature death because of increased size and accumulation of lipid droplets within cardiac myocytes.[4]
Peroxisome proliferator activated receptors (PPARs)
PPARs are a family of ligand activated receptors which include PPARα, PPARδ and PPARγ subtypes that are expressed in varying amounts in nuclear membranes of in different tissues.[5] PPAR activation occurs with free fatty acid binding, or fatty acid derivative ligands that have been broken down via the triacylglycerol lipolysis cascade.[1] Activated PPARs act as transcription factors to increase expression of specific genes within cells.[6] PPARα, a PPAR subtype, controls the expression of genes involved in cardiac fatty acid utilization,[6][7] and its activation, stimulates free fatty acid oxidation by increasing mitochondrial free fatty acid uptake and oxidation via two enzymes: carnitine palmitoyltransferase I (M-CPT I) and medium-chain acyl-CoA dehydrogenase (MCAD).[6]
