With around 55% carbohydrates form the largest diet component. The sugar molecules can be divided into polysaccharides, disaccharides and monosaccharides. The more complex molecules have to be cleaved to smaller disaccharides and monosaccharides by digestive enzymes. Only monosaccharides such as glucose and fructose can be taken up in the intestine. The molecular basis of monosaccharide transport is not completely understood. Whereas glucose is transported mainly via SGLT1 (sodium-glucose-cotransporter 1), fructose enters the enterocytes via GLUT5 (glucose transporter type 5). Also GLUT2 have been proposed to be involved in apical fructose absorption, but conflicting data exists. Besides other transporters, GLUT7 and GLUT9 have been described to be high affinity fructose transporters which could not confirmed by our group.
Lactose intolerance is characterized by diarrhoea, flatulence and abdominal pain. The condition is caused by malabsorption of milk sugar due to the absence of the mandatory enzyme lactase, which cleaves lactose to glucose and galactose. Comparable to that, subjects with fructose malabsorption show similar symptoms after ingestion of high amounts of fructose. In contrast to lactose intolerance, subjects with fructose malabsorption most likely display reduced fructose absorption due to impaired expression or misfolding of an intestinal fructose transporter. The underlying mechanism of fructose malabsorption, however, is unknown.
Our research group investigates several known or potential intestinal fructose transporters by direct DNA sequencing. In addition, we apply other methodological approaches such as the generation and investigation of human intestinal organoids from subjects with fructose malabsorption to determine the fructose transport and the expression of the corresponding transporters.
Moreover, we use a systematic approach by expression of wild-type as well as mutated proposed fructose transporters in Xenopus laevis oocytes or NIH-3T3 cells (immortalised fibroblasts of mice) and subsequent measurement of radiolabelled sugar transport. For example, to clarify which amino acids exactly enable fructose transport by GLUT5, we generated more than 100 chimeric proteins, that consist of parts of GLUT5 and GLUT7. With this approach, we were able to identify critical regions and single amino acids that facilitate fructose transport.
- Prof Hannelore Daniel (TUM, Munich, Germany)
- Prof Iris Antes (TUM, Munich, Germany)
Ebert K et al. Identification of essential amino acids for glucose transporter 5 (GLUT5)-mediated fructose transport. J Biol Chem. 2018;293(6):2115-2124. doi: 10.1074/jbc.RA117.001442. Pubmed
Ebert K et al. Reassessment of GLUT7 and GLUT9 as Putative Fructose and Glucose Transporters. J Membr Biol. 2017;250(2):171-182. doi: 10.1007/s00232-016-9945-7. Pubmed