Human Milk Oligosaccharides (HMO) carry lactose at the reducing end. Lactose is synthesized in the Golgi of mammary gland epithelial cells. In the presence of α-lactalbumin, which is specifically expressed during lactation, the substrate specificity of β1-4-galactosyltransferase shifts from N-acetylglucosamine to Glucose (Glc), now linking Galactose (Gal) to Glc to form lactose. The biosynthetic steps from lactose to HMO are currently unknown. The fucosylated and/or sialylated lactosamine backbone could be synthesized on glycoproteins or glycolipids and later transferred to lactose en bloc. The lactosamine backbone could also be synthesized onto lactose, one monosaccharide at a time.
Our lab is currently using human mammary gland epithelial cell cultures to induce lactose and HMOS expression and dissect the biosynthetic pathway.
The project is supported in part by the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD).