Cell Biology

How does Lactase work?

Lactase is a transmembrane protein located in the lipid bilayer membrane such that its active sites extend into the lumen of the intestine. When the enzyme lactase binds to the disaccharide lactose, its active sites cleave lactose into its two constituent sugars: glucose and galactose. Glucose and galactose are then free to be absorbed through the intestinal epithelial cells and transported into the bloodstream.

Absorption of Glucose and Galactose

After lactase is broken down into glucose and galactose, the glucose transporters SGLT1 and GLUT2 facilitate the diffusion of glucose and galactose through the enterocyte and into the bloodstream. This process is powered by the diffusion of these molecules down their concentration gradient: there is a higher concentration of glucose and galactose in the lumen of the intestine than in the enterocyte cell body, and there is a higher concentration of glucose and galactose in the enterocyte cell body than in the blood.

In the above diagrams: Lactase is a transmembrane protein on the interior border of the enterocyte. When lactose from the intestine contents comes into contact with the active site of lactase, it is broken down into glucose and galactose. The SGLT1 transmembrane protein (Sodium-Glucose Linked Transporter 1), transports glucose or galactose via facilitated diffusion from the intestine into the enterocyte. Then GLUT2 (Glucose Transporter 2) transports glucose or galactose via diffusion from the enterocyte to the bloodstream.

The Cell Biology of Lactose Intolerance

If lactose is not broken down in the small intestine, as is the case in lactose intolerant individuals, it is passed into the large intestine. This leads to several problems that are characteristic of lactose intolerance. The high concentration of lactose in the large intestine creates an osmotic gradient, which causes large volumes of water to move from the blood into the gut as the system begins to equalize the solute concentrations on either side of the intestine wall. This excess water leads to cramping and diarrhea, which causes pain and can lead to dehydration.

Furthermore, when lactose is not broken down by lactase in the small intestine it can be consumed by bacteria that live in the large intestine. Many of these bacteria use the process of sugar fermentation to produce ATP. The fermentation process produces large amounts of gaseous by-products, such as methane, carbon dioxide, and hydrogen. This leads to gas build-up in the gut, resulting in cramping and flatulence.

Lactase Regulation

Almost all known mammals – and 65% of humans – experience a decrease in lactase biosynthesis in the years after weaning. However, the remaining 35% of humans continue to produce lactase after weaning, and are therefore able to continue to consume milk and other dairy products into adulthood. In the case of lactase persistence, there is a continued production of lactase at high levels throughout adulthood.

Why is the production of lactase regulated in the first place? Why not just produce lactase in the enterocytes of all adult mammals? The answer is a matter of cellular energetics. Most mammals (humans notwithstanding) do not consume milk after they have been weaned. Therefore, the energy invested in biosynthesizing lactase is an unnecessary expenditure. This may seem like a very small amount of energy, but remember that everything that occurs in an organism is directed at the cellular level. Cellular energetics are in fact a major evolutionary pressure, and have shaped the evolution of the inner workings of cells since life began.