Allomorphy as a mechanism of post-translational control of enzyme activity

Enzyme regulation is vital for metabolic adaptability in living systems. Fine control of enzyme activity is often delivered through post-translational mechanisms, such as allostery or allokairy. β-phosphoglucomutase (βPGM) from Lactococcus lactis is a phosphoryl transfer enzyme required for complete catabolism of trehalose and maltose, through the isomerisation of β-glucose 1-phosphate to glucose 6-phosphate via β-glucose 1,6-bisphosphate. Surprisingly for a gatekeeper of glycolysis, no fine control mechanism of βPGM has yet been reported. Herein, we describe allomorphy, a post-translational control mechanism of enzyme activity. In βPGM, isomerisation of the K145-P146 peptide bond results in the population of two conformers that have different activities owing to repositioning of the K145 sidechain. In vivo phosphorylating agents, such as fructose 1,6-bisphosphate, generate phosphorylated forms of both conformers, leading to a lag phase in activity until the more active phosphorylated conformer dominates. In contrast, the reaction intermediate β-glucose 1,6-bisphosphate, whose concentration depends on the β-glucose 1-phosphate concentration, couples the conformational switch and the phosphorylation step, resulting in the rapid generation of the more active phosphorylated conformer. In enabling different behaviours for different allomorphic activators, allomorphy allows an organism to maximise its responsiveness to environmental changes while minimising the diversion of valuable metabolites

Chemical Approaches To Perturb, Profile, and Perceive Glycans

Glycosylation is an essential form of post-translational modification that regulates intracellular and extracellular processes. Regrettably, conventional biochemical and genetic methods often fall short for the study of glycans, because their structures are often not precisely defined at the genetic level. To address this deficiency, chemists have developed technologies to perturb glycan biosynthesis, profile their presentation at the systems level, and perceive their spatial distribution. These tools have identified potential disease biomarkers and ways to monitor dynamic changes to the glycome in living organisms. Still, glycosylation remains the underexplored frontier of many biological systems. In this Account, we focus on research in our laboratory that seeks to transform the study of glycan function from a challenge to routine practice

Problématiques digestives et nutritionnelles de l’enfant en situation de handicap [Digestive and nutritional problems of children with cerebral palsy]

Digestive and nutritional problems of children with cerebral palsy put them at risk of malnutrition. Identification of these problems through measurements of weight, height, and body composition is essential. Feeding difficulties may be caused by a combination of oral and digestive problems, such as swallowing difficulties, gastroesophageal reflux, and constipation. If oral feeding is difficult or unsafe, a nasogastric tube or gastrostomy may be necessary. Once the feeding regimen has been established, energy needs must be assessed on an individual basis. This nutritional management involves a multidisciplinary team of health care professionals, the child, and the family

Pediatric Patients with Eosinophilic Esophagitis and Their Parents Identify Symptoms as the Most Important Treatment Outcome.

Given the lack of data, we aimed to explore which therapeutic endpoints pediatric patients with eosinophilic esophagitis (EoE) and their parents consider to be relevant. We created an educational brochure on EoE and a questionnaire, both of which were content-validated by pediatric patients and parents. Validated documents were sent to 112 patients and parents. They ranked the importance (5 levels) of short (during next 3 months) and long-term (≥1 year) treatment effect on symptoms, quality of life, endoscopic inflammation, stricture formation, histological inflammation, and fibrosis. A total of 45 parents and 30 pediatric patients ≥11 years completed the questionnaires. Pediatric patients identified improvement in the following domains as most important in the short- and long-term, respectively: symptoms (73% vs. 77%), QoL (53% vs. 57%), histologic inflammation (47% vs. 50%), histologic fibrosis (40% vs. 33%), endoscopic inflammation (47% vs. 40%), and strictures (33% vs. 40%). Parents of children ≥11 years old classified improvement in the following domains as most important in the short- and long-term, respectively: symptoms (70% vs. 83%), QoL (63% vs. 80%), histologic inflammation (67% vs. 77%), histologic fibrosis (47% vs. 63%), endoscopic inflammation (77% vs. 80%), and strictures (40% vs. 53%). Agreement between caregiver and children on the short-term importance of treatment outcomes was as follows: symptoms (77%), QoL (40%), histologic inflammation and fibrosis (47% and 43%), endoscopic inflammation and strictures (50% and 40%). Pediatric patients and parents attributed most importance to improvement in symptoms and QoL. Agreement between parents and patients regarding therapy goals is limited