solute carrier family 5 member 1
The SLC5A1 gene provides instructions for producing a protein called sodium/glucose cotransporter protein 1 (SGLT1). This protein is found mainly in the intestinal tract and the kidneys. It spans the membrane of cells and moves (transports) two sugars called glucose and galactose from outside the cell to inside the cell. Sodium and water are transported across the cell membrane along with the sugars in this process. Glucose and galactose are simple sugars; they are present in many foods, or they can be obtained from the breakdown of other sugars (such as lactose, the sugar found in milk) and carbohydrates in the diet during digestion.
In the intestinal tract, the SGLT1 protein helps take in (absorb) glucose and galactose from the diet. The protein is found in intestinal epithelial cells, which are cells that line the walls of the intestine. These cells have fingerlike projections called microvilli that absorb nutrients from food as it passes through the intestine. Based on their appearance, groups of these microvilli are known collectively as the brush border. The SGLT1 protein is involved in the process of transporting glucose and galactose across the membrane of the intestinal epithelial cells so the sugars can be absorbed and used by the body.
The SGLT1 protein also plays a role in maintaining normal glucose levels in the body. In the kidneys, the SGLT1 protein is located in structures called proximal tubules. These structures help ensure that all nutrients have been extracted from waste fluids before the fluids are released from the body as urine. The SGLT1 protein, and a similar protein called SGLT2, transport glucose from proximal tubules, ensuring that the sugar is absorbed into the bloodstream and not released into the urine. The activity of the SGLT1 protein is the last step of glucose absorption in the kidneys.
More than 60 mutations in the SLC5A1 gene have been found to cause glucose-galactose malabsorption. This condition begins in infancy and is characterized by severe diarrhea, resulting in weight loss and dehydration that can be life-threatening. SLC5A1 gene mutations impair or eliminate the function of the SGLT1 protein. Some mutations result in a protein that is folded into the incorrect shape, other mutations result in a protein that is abnormally short.
The altered SGLT1 protein's ability to transport glucose and galactose is reduced or absent. The sugars are not fully absorbed by intestinal epithelial cells, but instead accumulate in the intestinal tract. In addition, water that normally would have been transported with the sugars remains in the intestinal tract, resulting in dehydration of the body's tissues and severe diarrhea. In the kidneys, the SGLT1 protein cannot filter glucose; however, other proteins in the proximal tubules, including the SGLT2 protein, are able to absorb enough glucose into the bloodstream, so that glucose in the urine (glucosuria) is mild, if present at all, in people with glucose-galactose malabsorption.