title: Phenylbutyric Acid: simple structure - multiple effects.
abstract: Phenylbutyrate (PBA) is an aromatic short-chain fatty acid which is a chemical derivative of butyric acid naturally produced by colonic bacteria fermentation. At the intestinal level butyrate exerts a multitude of activities including amelioration of mucosal inflammation, regulation of transepithelial fluid transport, improvement in oxidative status and colon cancer prevention. Moreover, increasing number of studies report the beneficial role of butyric acid in prevention or inhibition of other types of malignancies, leading to cancer cell growth arrest and apoptosis. Similarly, phenylbutyrate displays potentially favorable effects on many pathologies including cancer, genetic metabolic syndromes, neuropathies, diabetes, hemoglobinopathies, and urea cycle disorders. The mechanisms by which PBA exerts these effects are different. Some of them are connected with the regulation of gene expression, playing the role of a histone deacetylase inhibitor, while others contribute to the ability of rescuing conformational abnormalities of proteins, serving as chemical chaperone, and some are dedicated to its metabolic characteristic enabling excretion of toxic ammonia, thus acting as ammonia scavenger. Phenylbutyrate may exert variable effects depending on the cell type, thus the term "butyrate paradox" has been proposed. These data indicate a broad spectrum of beneficial effects evoked by PBA with a high potential in therapy. In this review, we focus on cellular and systemic effects of PBA treatment with special attention to the three main branches of its molecular activity: ammonia scavenging, chaperoning and histone deacetylase inhibiting, and describe its particular role in various human diseases.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Kusaczuk
authors.forename: Marek
authors.initials: M
authors.lastname: Bartoszewicz
authors.affiliation: Department of Pharmaceutical Biochemistry, Medical University of Biaystok, Mickiewicza 2A, 15-222 Biaystok, Poland. mapasko@gmail.com.
authors.forename: Marzanna
authors.initials: M
authors.lastname: Cechowska-Pasko
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000473:pathology; D006801:Humans; D019636:Neurodegenerative Diseases / Q000188:drug therapy / Q000473:pathology; D010654:Phenylbutyrates / Q000737:chemistry* / Q000627:therapeutic use*
chemical_list: D010654:Phenylbutyrates; C075773:4-phenylbutyric acid