Title:Phenylbutyric Acid: Simple Structure - Multiple Effects
Volume: 21
Issue: 16
Author(s): Magdalena Kusaczuk, Marek Bartoszewicz and Marzanna Cechowska-Pasko
Affiliation:
Keywords:
Ammonia scavenger, butyric acid, chemical chaperone, ER stress, histone deacetylase inhibitor, phenylbutyrate.
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.
