The UDP-Glycosyltransferase (UGT) Superfamily: New Members, New Functions, and Novel Paradigms.

UDP-glycosyltransferases (UGTs) catalyze the covalent addition of sugars to a broad range of lipophilic molecules. This biotransformation plays a critical role in elimination of a broad range of exogenous chemicals and by-products of endogenous metabolism, and also controls the levels and distribution of many endogenous signaling molecules. In mammals, the superfamily comprises four families: UGT1, UGT2, UGT3, and UGT8. UGT1 and UGT2 enzymes have important roles in pharmacology and toxicology including contributing to interindividual differences in drug disposition as well as to cancer risk. These UGTs are highly expressed in organs of detoxification (e.g., liver, kidney, intestine) and can be induced by pathways that sense demand for detoxification and for modulation of endobiotic signaling molecules. The functions of the UGT3 and UGT8 family enzymes have only been characterized relatively recently; these enzymes show different UDP-sugar preferences to that of UGT1 and UGT2 enzymes, and to date, their contributions to drug metabolism appear to be relatively minor. This review summarizes and provides critical analysis of the current state of research into all four families of UGT enzymes. Key areas discussed include the roles of UGTs in drug metabolism, cancer risk, and regulation of signaling, as well as the transcriptional and posttranscriptional control of UGT expression and function. The latter part of this review provides an in-depth analysis of the known and predicted functions of UGT3 and UGT8 enzymes, focused on their likely roles in modulation of levels of endogenous signaling pathways.

Wnt/ß-catenin signaling induces the myomiRs miR-133b and miR-206 to suppress Pax7 and induce the myogenic differentiation program.

The downregulation of Pax7 expression is an essential requirement for adult muscle progenitor cell differentiation during muscle regeneration. We previously found that canonical Wnt signals drive myogenic differentiation by positively regulating the expression of myogenic target genes, and also by negatively regulating Pax7 expression. To better understand how Wnt signals repress Pax7 expression, we screened for Wnt-regulated microRNAs (miRNAs) that could target the Pax7 3'untranslated region (UTR). Using wild-type and ß-catenin null primary mouse myoblasts, we identified several Wnt/ß-catenin regulated miRNAs, the most abundant of which were miR-133b and miR-206. While miR-206 was previously identified as Pax7 regulator, miR-133b has never been shown to regulate the Pax7 transcript. We show here that miR-133b is a more potent inhibitor of Pax7 expression than miR-206, and that it acts via a site adjacent to the miR-206 binding site in the Pax7 3'UTR. The primary transcript encoding miR-133b/miR-206 is specifically induced by Wnt/ß-catenin, while the miR-1/miR-133a transcript is not; moreover, Wnt signals increase the secretion of mature miR-133b/miR-206 into exosomes. Overall, we conclude that miR-133b and to a lesser degree miR-206, but not miR-1 or miR-133a, are key components of the canonical Wnt-mediated pathway that allows differentiation to proceed by relieving Pax7-mediated repression of the myogenic program. Secretion of these miRNAs into exosomes may allow them to directly control the differentiation of neighboring cells.

Direct biodiesel production from wet spent coffee grounds.

Utilization of waste spent coffee grounds (SCG) remains limited and requires pre-treatment before being discarded to avoid pollution to the environment. Lipids contained in SCG could be converted to biodiesel through an in situ transesterification method. Current in situ transesterification of wet SCG biomass, conducted at high reaction temperature to reduce the water effect and reduce reaction time, is energy intensive. A new approach, which combines simultaneous extraction-transesterification in a single step using soxhlet apparatus, was developed to produce biodiesel directly from wet SCG biomass. A homogeneous base catalyst at a concentration of 0.75 M showed better catalytic activity than acid, with hexane as a co-solvent on fatty acid (FA) extraction efficiency and FA to fatty acid methyl ester (FAME) conversion efficiency. Studying the factorial effect of ratio of methanol to hexane and reaction time led to the highest FA to FAME conversion efficiency of 97% at a ratio of 1 : 2 and 30 min reaction time. In addition, the catalyst could be used five times without losing its activity. In term of energy consumption, the reactive extraction soxhlet (RES) method could save 38-99% of energy compared to existing methods.