Silencing ScGUX2 reduces xylan glucuronidation and improves biomass saccharification in sugarcane.

There is an increasing need for renewable energy sources to replace part of our fossil fuel-based economy and reduce greenhouse gas emission. Sugarcane bagasse is a prominent feedstock to produce cellulosic bioethanol, but strategies are still needed to improve the cost-effective exploitation of this potential energy source. In model plants, it has been shown that GUX genes are involved in cell wall hemicellulose decoration, adding glucuronic acid substitutions on the xylan backbone. Mutation of GUX genes increases enzyme access to cell wall polysaccharides, reducing biomass recalcitrance in Arabidopsis thaliana. Here, we characterized the sugarcane GUX genes and silenced GUX2 in commercial hybrid sugarcane. The transgenic lines had no penalty in development under greenhouse conditions. The sugarcane GUX1 and GUX2 enzymes generated different patterns of xylan glucuronidation, suggesting they may differently influence the molecular interaction of xylan with cellulose and lignin. Studies using biomass without chemical or steam pretreatment showed that the cell wall polysaccharides, particularly xylan, were less recalcitrant in sugarcane with GUX2 silenced than in WT plants. Our findings suggest that manipulation of GUX in sugarcane can reduce the costs of second-generation ethanol production and enhance the contribution of biofuels to lowering the emission of greenhouse gases.

Characterisation of UDP-glucuronosyltransferase activity in sea turtle Chelonia mydas.

Uridine diphosphate glucuronosyltransferase (UGT) enzymes conjugate many lipophilic chemicals, such as drugs, environmental contaminants, and endogenous compounds, promoting their excretion. The complexity of UGT kinetics, and the location of enzyme active site in endoplasmic reticulum lumen, requires an accurate optimisation of enzyme assays.In the present study, we characterised UGT activity in liver microsomes of green turtles (Chelonia mydas), an endangered species. The conditions for measuring UGT activity were standardised through spectrofluorimetric methods, using the substrates 4-methylumbelliferone (4-MU) and uridine diphosphate glucuronic acid (UDPGA) at 30 °C and pH 7.4.The green turtles showed UGT activity at the saturating concentrations of substrates of 250 µM to 4-MU and 7 mM to UDPGA. The alamethicin, Brij®58, bovine serum albumin (BSA), and magnesium increased UGT activity. The assay using alamethicin (22 µg per mg of protein), magnesium (1 mM), and BSA (0.25%) reached the highest Vmax (1203 pmol·min-1mg·protein-1). Lithocholic acid and diclofenac inhibited UGT activity in green turtles.This study is the first report of UGT activity in the liver of green turtles and provides a base for future studies to understand the mechanisms of toxicity by exposure to contaminants in this charismatic species.

Recent Evidence of the Beneficial Effects Associated with Glucuronic Acid Contained in Kombucha Beverages.

PURPOSE OF THE REVIEW: Glucuronic acid is contained naturally in kombucha beverages due to the associations between bacteria and yeasts during its fermentation. The purpose of this review is to describe the literature related to the hepatoprotective effect associated with glucuronic acid present in different kombucha beverages. RECENT FINDINGS: Although previous research supports beneficial hepatoprotective effects of glucuronic acid consumption from kombucha, these effects are mainly attributed to the tea phytochemicals. However, there are some improvements in methodological deficiencies in some in vivo studies that should be considered. There is no sufficient evidence to generalize the adverse effects of kombucha consumption. Consumption of kombucha could be considered a safe practice in healthy populations due to its hepatoprotective effects. The content of the beneficial or toxic components is very variable because it depends on its manufacturing process. In persons with side sickness, other conditions such as pregnancy, and hypersensitivity to some kombucha components, a restriction in its consumption must be advisable.

Enhanced UGT1A1 Gene and Protein Expression in Endometriotic Lesions.

The cellular function in endometriosis lesions depends on a highly estrogenic milieu. Lately, it is becoming evident that, besides the circulating levels of estrogens, the balance of synthesis versus inactivation (metabolism) of estrogens by intralesion steroid-metabolizing enzymes also determines the local net estrogen availability. In order to extend the knowledge of the role of estrogen-metabolizing enzymes in endometriosis, we investigated the gene and protein expression of a key uridine diphospho-glucuronosyltransferase (UGT) for estrogen glucuronidation, UGT1A1, in eutopic endometrial samples obtained from nonaffected and endometriosis-affected women and also from endometriotic lesions. Although UGT1A1 messenger RNA (mRNA) expression was detected at similar frequencies in endometriotic lesions and in eutopic endometrial samples, the levels of mRNA expression were greater in deep-infiltrating endometriotic lesions and in non-deep-infiltrating lesions when compared with either control endometrium or eutopic endometrium from women with endometriosis. Overall, we observed that protein expression of UGT1A1 was significantly more frequent in samples from endometriotic lesions in comparison with endometria. In addition, expression of UGT1A1 protein was greater in deep-infiltrating than in non-deep-infiltrating endometriotic lesions. We suggest that the finding of increased expression of UGT1A1 in lesions versus endometria might be related to impairment of regulatory mechanisms, in response to a highly estrogenic milieu, and that this enzyme may be a new target for therapy.

UDP-glucuronosyltransferases: Structure, Function and Drug Design Studies.

UDP-glucuronosyltransferases (UGTs) are important phase II metabolic enzymes responsible for approximately 40-70% of endo and xenobiotic reactions. It catalyzes the transfer of glucuronic acid to lipophilic substrates, converting them into hydrophilic compounds that are excreted. There are 22 active human UGTs that belong to 4 families. This review focuses on human UGTs, highlighting the most current issues in order to connect all information available and allowing a discussion on the challenges already solved and those in which we need to move forward. Although, several UGTs studies have been conducted, the most recent ones addressing drug-drug interactions and polymorphism issues, there are still bottlenecks to overcome. Tridimensional structure is difficult to obtain due to overexpression, purification, and crystallization problems as well as the action mechanism - since overlapping of substrate specificities renders impasses on the identification of which isoform is responsible for a particular drug metabolic pathway. For this reason, bioinformatic tools are gaining more space, since it is a faster and less expensive reliable methodology that complements in vitro and in vivo researches. Combinations of quantum and molecular methods have become increasingly common, leading to the incorporation of enzyme features comprising their structure, dynamics and chemical reactions. Breakthroughs related to the enzyme, not only enable the discovery of new drugs essential for the treatment of various diseases, but also provide an improved action of the existing drugs.

Corrigendum: Herbal medicines in Brazil: pharmacokinetic profile and potential herb-drug interactions.

[This corrects the article on p. 162 in vol. 5, PMID: 25071580.].

Herbal medicines in Brazil: pharmacokinetic profile and potential herb-drug interactions.

A plethora of active compounds found in herbal medicines can serve as substrate for enzymes involved in the metabolism of xenobiotics. When a medicinal plant is co-administered with a conventional drug and little or no information is known about the pharmacokinetics of the plant metabolites, there is an increased risk of potential herb-drug interactions. Moreover, genetic polymorphisms in a population may act to predispose individuals to adverse reactions. The use of herbal medicines is rapidly increasing in many countries, particularly Brazil where the vast biodiversity is a potential source of new and more affordable treatments for numerous conditions. Accordingly, the Brazilian Unified Public Health System (SUS) produced a list of 71 plant species of interest, which could be made available to the population in the near future. Physicians at SUS prescribe a number of essential drugs and should herbal medicines be added to this system the chance of herb-drug interactions further increases. A review of the effects of these medicinal plants on Phase 1 and Phase 2 metabolic mechanisms and the transporter P-glycoprotein was conducted. The results have shown that approximately half of these medicinal plants lack any pharmacokinetic data. Moreover, most of the studies carried out are in vitro. Only a few reports on herb-drug interactions with essential drugs prescribed by SUS were found, suggesting that very little attention is being given to the safety of herbal medicines. Here we have taken this information to discuss the potential interactions between herbal medicines and essential drugs prescribed to Brazilian patients whilst taking into account the most common polymorphisms present in the Brazilian population. A number of theoretical interactions are pinpointed but more pharmacokinetic studies and pharmacovigilance data are needed to ascertain their clinical significance.

Terapêutica felina: diferenças farmacológicas e fisiológicas / Feline therapy: pharmacological and physiological differences

É sabido que gatos apresentam respostas diferentes das manifestadas pelos cães, quando tratados com diversos fármacos. Entretanto, as doses de muitos medicamentos, para terapêutica de felídeos, são obtidas a partir das utilizadas para cães, ocasionando uma série de reações adversas. Essas rea¬ções se manifestam de várias maneiras, conforme dose utilizada, tipo de fármaco, via de administra¬ção, idade e condição física do animal, devido às diferenças no metabolismo entre as espécies. Gatos apresentam uma deficiência relativa na atividade de enzimas glicuronil transferase, que catalisam as reações de conjugação mais importantes nos mamíferos. Além disso, eles são muito susceptíveis à me¬tahemoglobinemia e à formação de corpúsculos de Heinz, após a administração de alguns fármacos, por possuir um número maior de grupos sulfidril comparado aos cães e humanos. O objetivo deste trabalho é revisar as características metabólicas e fisiológicas dos felídeos domésticos e os principais fármacos capazes de causar reações adversas e intoxicações nestes animais

It is known that cats respond different1y from dogs to several drugs. Many medicine dosages recom¬mended for dogs are extrapolated to cats, and this usually causes adverse reactions in felines. Those reactions can be manifested by various ways according to a series of factors like the type of drug used, the dose of drug, age, corporal status and route of administration. Those manifestations occur mainly due to differences into the metabolism among the species. The cat has a relative deficiency in the activity of some glycuronyl transferase, which catalyzes the most conjugation reactions in mam¬mals. Besides, the species are very susceptible to methemoglobinemia and. Heinz body formation after administration of some drugs due own a major number of sulfidril groups compared with dogs and men. The intention this paper is review eats physiologic and. metabolic features and the main drugs that can cause adverse reactions and intoxication in cats

Terapêutica felina: diferenças farmacológicas e fisiológicas / Feline therapy: pharmacological and physiological differences

É sabido que gatos apresentam respostas diferentes das manifestadas pelos cães, quando tratados com diversos fármacos. Entretanto, as doses de muitos medicamentos, para terapêutica de felídeos, são obtidas a partir das utilizadas para cães, ocasionando uma série de reações adversas. Essas rea¬ções se manifestam de várias maneiras, conforme dose utilizada, tipo de fármaco, via de administra¬ção, idade e condição física do animal, devido às diferenças no metabolismo entre as espécies. Gatos apresentam uma deficiência relativa na atividade de enzimas glicuronil transferase, que catalisam as reações de conjugação mais importantes nos mamíferos. Além disso, eles são muito susceptíveis à me¬tahemoglobinemia e à formação de corpúsculos de Heinz, após a administração de alguns fármacos, por possuir um número maior de grupos sulfidril comparado aos cães e humanos. O objetivo deste trabalho é revisar as características metabólicas e fisiológicas dos felídeos domésticos e os principais fármacos capazes de causar reações adversas e intoxicações nestes animais(AU)

It is known that cats respond different1y from dogs to several drugs. Many medicine dosages recom¬mended for dogs are extrapolated to cats, and this usually causes adverse reactions in felines. Those reactions can be manifested by various ways according to a series of factors like the type of drug used, the dose of drug, age, corporal status and route of administration. Those manifestations occur mainly due to differences into the metabolism among the species. The cat has a relative deficiency in the activity of some glycuronyl transferase, which catalyzes the most conjugation reactions in mam¬mals. Besides, the species are very susceptible to methemoglobinemia and. Heinz body formation after administration of some drugs due own a major number of sulfidril groups compared with dogs and men. The intention this paper is review eats physiologic and. metabolic features and the main drugs that can cause adverse reactions and intoxication in cats(AU)