The peroxisome proliferator-activated receptor alpha (PPARα) is a ligand-activated transcription factor involved in the regulation of a variety of processes, ranging from inflammation and immunity to nutrient metabolism and energy homeostasis. PPARα serves as a molecular target for hypolipidemic fibrates drugs which bind the receptor with high affinity. Furthermore, PPARα binds and is activated by numerous fatty acids and fatty acid-derived compounds. PPARα governs biological processes by altering the expression of a large number of target genes. Accordingly, the specific role of PPARα is directly related to the biological function of its target genes. Here, we present an overview of the involvement of PPARα in lipid metabolism and other pathways through a detailed analysis of the different known or putative PPARα target genes. The emphasis is on gene regulation by PPARα in liver although many of the results likely apply to other organs and tissues as well.

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Peroxisome Proliferator-Activated Receptor Alpha Target Genes

Epoxyeicosatrienoic acids (EETs): metabolism and biochemical function.

Xenobiotics, which are absorbed into biological systems by passive diffusion across membranes are usually lipid soluble and not ideally suited for excretion. Indeed very lipophilic substances may remain in the mammalian body for many years. After a xenobiotic has been absorbed, it may undergo biotransformation to products which are rapidly excreted and therefore elimination of the compound from the animal is facilitated. However, biotransformation may also change the biological activity of the substance. Hence, the metabolic fate of the compound can have an important bearing on its toxic potential, the disposition of the compound in the body and the excretion of the compound. The metabolic reactions involved are usually divided into phase 1 and phase 2 reactions, the latter being conjugation reactions. The products of metabolism are usually more water soluble than the original compound. Although usually detoxifying, these reactions, especially phase 1 ones, sometimes increase toxicity.


Keywords:

biotransformation;
metabolism;
Phase 1;
Phase 2;
conjugation;
cytochrome;
hydroxylation;
oxidation;
dealkylation

Biotransformation of Xenobiotics

Regulation of energy metabolism by long-chain fatty acids

https://escholarship.org/content/qt14t5c95n/qt14t5c95n.pdf?t=qlunya

L. Ashley Cowart

Papers

The CYP4A Isoforms Hydroxylate Epoxyeicosatrienoic Acids to Form High Affinity Peroxisome Proliferator-activated Receptor Ligands