Digestive enzyme | EPFL Graph Search

Digestive enzymes are a group of enzymes that break down polymeric macromolecules into their smaller building blocks, in order to facilitate their absorption into the cells of the body. Digestive enzymes are found in the digestive tracts of animals (including humans) and in the tracts of carnivorous plants, where they aid in the digestion of food, as well as inside cells, especially in their lysosomes, where they function to maintain cellular survival. Digestive enzymes of diverse specificities are found in the saliva secreted by the salivary glands, in the secretions of cells lining the stomach, in the pancreatic juice secreted by pancreatic exocrine cells, and in the secretions of cells lining the small and large intestines. Digestive enzymes are classified based on their target substrates: *Lipases split fatty acids into fats and oils. *Proteases and peptidases split proteins into small peptides and amino acids. *Amylases split carbohydrates such as starch and sugars into simple su

Redefining the metabolic landscape through TGF-beta/Activin signaling in Drosophila melanogaster

Wen Bin Chng

Multicellular organisms assess their nutritional state and adapt their metabolic landscape to match their energy demands. In this thesis, we address a longstanding conundrum of how an organism coordinates digestive enzyme expression in response to its nutritional status. Hydrolysis of food materials by endogenous or microbial-derived digestive enzymes precedes absorption through the gut lumen. Thus, modulation of endogenous digestive mechanism represents a pragmatic step to limit the uptake of nutrients when nutrients are in abundance. In Drosophila melanogaster, it is known that dietary glucose represses amylase transcript and enzymatic activity, in a process known as glucose repression. Here, we show that glucose reduces the expression of many carbohydrases, lipases, and glucose transporters, presumably to prevent nutritional overload after feeding. We found that the repression of carbohydrases is effected by nutritious sugars through the induction of the TGF-beta ligand, Dawdle. Interestingly, glucose repression of digestive enzymes is dependent upon the induction of Dawdle in the fat body, a tissue functionally analogous to the mammalian liver and adipose tissue. Dawdle is then transported via the circulation to activate TGFÎ²/Activin signaling in the midgut, leading to the repression of digestive enzymes expression. We later discovered that Dawdle expression in the fat body is regulated by the evolutionarily conserved Mio-bigmax transcription factor complex. In addition, expression of Dawdle must be tightly coordinated to reflect the nutritional state of adult flies, as flies overexpressing Dawdle are sensitive to starvation and have their TAG and glycogen stores rapidly depleted upon nutrient limitation. Thus, our results are consistent with a model whereby fat body derived Daw functions as a nutritional cue for carbohydrates to modulate metabolic responses in distal tissues. Its induction provides the nutritional signal to repress carbohydrate digestive capacity and stimulate peripheral insulin signaling. In conclusion, our study identifies the TGFÎ²/Activin signaling as a critical mechanism for carbohydrate homeostasis. Our results indicate that the fat body functions as a carbohydrate sensing tissue, which through the secretion of the TGFÎ² ligand, Daw, regulates organism-wide carbohydrate metabolism. Our work in Drosophila is likely to have a broader scientific impact by placing a pathway known for its role in development, immunity, and cancer, as an integral component for sugar sensing and metabolism.

EPFL2015

Multitarget Drug Discovery for Tuberculosis and Other Infectious Diseases

Stewart Cole, Benoit Lechartier, Kai Li, Wei Zhu

We report the discovery of a series of new drug leads that have potent activity against Mycobacterium tuberculosis as well as against other bacteria, fungi, and a malaria parasite. The compounds are analogues of the new tuberculosis (TB) drug SQ109 (1), which has been reported to act by inhibiting a transporter called MmpL3, involved in cell wall biosynthesis. We show that 1 and the new compounds also target enzymes involved in menaquinone biosynthesis and electron transport, inhibiting respiration and ATP biosynthesis, and are uncouplers, collapsing the pH gradient and membrane potential used to power transporters. The result of such multitarget inhibition is potent inhibition of TB cell growth, as well as very low rates of spontaneous drug resistance. Several targets are absent in humans but are present in other bacteria, as well as in malaria parasites, whose growth is also inhibited.

Amer Chemical Soc2014

Transforming Growth Factor beta/Activin Signaling Functions as a Sugar-Sensing Feedback Loop to Regulate Digestive Enzyme Expression

Maroun Bou Sleiman, Wen Bin Chng, Bruno Lemaitre

Organisms need to assess their nutritional state and adapt their digestive capacity to the demands for various nutrients. Modulation of digestive enzyme production represents a rational step to regulate nutriment uptake. However, the role of digestion in nutrient homeostasis has been largely neglected. In this study, we analyzed the mechanism underlying glucose repression of digestive enzymes in the adult Drosophila midgut. We demonstrate that glucose represses the expression of many carbohydrases and lipases. Our data reveal that the consumption of nutritious sugars stimulates the secretion of the transforming growth factor beta (TGF-beta) ligand, Dawdle, from the fat body. Dawdle then acts via circulation to activate TGF-beta/Activin signaling in the midgut, culminating in the repression of digestive enzymes that are highly expressed during starvation. Thus, our study not only identifies a mechanism that couples sugar sensing with digestive enzyme expression but points to an important role of TGF-beta/Activin signaling in sugar metabolism.

Elsevier2014

Redefining the metabolic landscape through TGF-beta/Activin signaling in Drosophila melanogaster

Wen Bin Chng

EPFL2015