A comprehensive overview of substrate specificity of glycoside hydrolases and transporters in the small intestine
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Cellular and Molecular Life Sciences
REVIEW
A comprehensive overview of substrate specificity of glycoside hydrolases and transporters in the small intestine “A gut feeling” Hidde Elferink1 · Jeroen P. J. Bruekers1 · Gerrit H. Veeneman2 · Thomas J. Boltje1 Received: 10 April 2020 / Revised: 21 May 2020 / Accepted: 25 May 2020 © The Author(s) 2020
Abstract The human body is able to process and transport a complex variety of carbohydrates, unlocking their nutritional value as energy source or as important building block. The endogenous glycosyl hydrolases (glycosidases) and glycosyl transporter proteins located in the enterocytes of the small intestine play a crucial role in this process and digest and/or transport nutritional sugars based on their structural features. It is for these reasons that glycosidases and glycosyl transporters are interesting therapeutic targets to combat sugar related diseases (such as diabetes) or to improve drug delivery. In this review we provide a detailed overview focused on the molecular structure of the substrates involved as a solid base to start from and to fuel research in the area of therapeutics and diagnostics. In most diets, carbohydrates constitute a major source of energy in the form of digestible oligo- and disaccharides. For example, amylose (α-1,4-linked glucose) and amylopectin (α-1,6 branched α-1,4-linked glucose) are components of starches and an important source of glucose. Disaccharides such as sucrose (α-Glc-1 → 2-β-Fruc), lactose (β-Gal-1 → 4-Glc) and trehalose (α-Glc-1 → 1-α-Glc) are precursors for fructose, galactose and glucose, respectively. To unlock the nutritional value of these molecules, the body expresses enzymes to hydrolyze the oligo- and disaccharides into their respective monosaccharide constituents followed by uptake via a series of monosaccharide transporters [1]. Upstream of intestinal digestion, large α-linked polysaccharides such as amylose are degraded to disaccharides (e.g. maltose) and oligosaccharides by salivary- and pancreatic amylase [2]. In addition, a small amount is hydrolyzed in the stomach [3]. As these processes upstream of the small intestine produce negligible quantities of transportable sugars, they are beyond the scope of this review. The bulk of * Thomas J. Boltje [email protected] 1
Institute for Molecules and Materials, Radboud University, Heyendaalseweg 135, 6525 Nijmegen, The Netherlands
PharmaCytics B.V., Noviotech Campus, Nijmegen, The Netherlands
2
oligo- and disaccharide digestion and uptake occurs in the small intestine by the action of membrane bound glycosyl hydrolases present in the brush border of the jejunum (Fig. 1). The breakdown of starch oligosaccharides is carried out by enzymes capable of cleaving the α-1,6-Glc and α-1,4-Glc linkages such as the maltase-glucoamylase complex (MGAM) and sucrase isomaltase (SI). In addition, SI is also capable of cleaving sucrose into glucose and fructose. Lactose is converted by lactase-phlorizin hydrolase (LPH) yielding galactose and glucose. Trehalose, a disacchari
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