β-Galactosidase: intestinal enzyme complex involved in the hydrolysis of lactose to glucose and galactose. Commonly called lactase
Leloir pathway: primary pathway for the conversion of galactose to glucose
Galactosemia: results from defects in any of the 3 primary genes involved in conversion of galactose to glucose
A major form of galactose found in these complex biomolecules is N-acetylgalactosamine (GalNAc). GalNAc is not acquired from the diet but is formed from dietary galactose. The major source of galactose in the human diet is from the disaccharide, lactose, found in dairy products. This sugar comprises around 2% to 8% of milk solids. Lactose is a disaccharide of glucose and galactose. Upon consumption of lactose, it is hydrolyzed to glucose and galactose via the action of the intestinal enzyme complex called β-galactosidase (lactase-glycosylceramidase). The enzyme complex is attached to the surface of intestinal brush border cells via a GPI linkage (see Chapter 38). There are 2 enzymatic activities associated with the β-galactosidase complex, one that hydrolyzes the β-glycosidic linkage in lactose (thereby releasing glucose and galactose), while the other activity hydrolyzes the β-glycosidic bond connecting galactose or glucose to ceramide in ingested glycolipids. Galactose is subsequently absorbed by intestinal enterocytes via the action of the same sodium (Na+)-dependent glucose transporter (SGLT1) that is responsible for glucose absorption. Galactose enters the blood from intestinal enterocytes via GLUT2-mediated transport as for glucose and fructose.
Entry of Galactose Into Glycolysis
Although glucose is the form of sugar stored as glycogen within cells, galactose is utilized via conversion to glucose, which can then be oxidized in glycolysis or stored as glycogen. Indeed, up to 30% of ingested galactose is incorporated into glycogen. Galactose enters glycolysis by its conversion to glucose-1-phosphate (G1P). This occurs through a series of steps that is referred to as the Leloir pathway, named after Luis Federico Leloir who determined the overall process of galactose utilization. First, the galactose is phosphorylated by galactokinase to yield galactose-1-phosphate. The galactokinase protein is encoded by the GALK1 gene. There is another gene identified as GALK2 that was originally thought to encode a second galactokinase but was subsequently shown to be a GalNAc kinase. Epimerization of galactose-1-phosphate to G1P requires the transfer of UDP from uridine diphosphoglucose (UDP-glucose) catalyzed by galactose-1-phosphate uridyltransferase (GALT). The GALT-catalyzed reaction generates UDP-galactose and G1P. The UDP-galactose is epimerized to UDP-glucose by UDP-galactose-4 epimerase (GALE). The UDP portion is exchanged for phosphate-generating glucose-1-phosphate, which then is converted to G6P by phosphoglucose mutase. GALE catalyzes 2 distinct but analogous epimerization reactions, the epimerization of UDP-galactose to UDP-glucose and the epimerization of UDP-N-acetylgalactosamine to UDP-N-acetylglucosamine (Figure 12-1).
Pathway of conversion of (A) galactose to glucose in the liver. Murray RK, Bender DA, Botham KM, Kennelly PJ, Rodwell VW, Weil PA. Harper's Illustrated ...