Lactose synthesis pathway in mammary glands

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(Last Updated On: October 21, 2017)

Lactose is a milk sugar present in only the milk. It is a disaccharide composed of D-galactose and D-glucose linked through β 1-4 glycosidic linkage. Lactose synthesized involves a series of reactions and the pathway is lactose synthesis pathway. Lactose doesn’t  have a free hydroxy group at an anomeric carbon (carbon number 2). Because of that, oxidizing agents can easily oxidize them to a sugar acid.


Lactose synthesis occurs in mammary gland

Lactose synthesis occurs in the mammary gland. In the lumen of the Golgi complex, there is a membrane-bound enzyme lactose synthase. This is a type of galactosyltransferase responsible for the lactose synthesis. Lactose synthase catalyzes the condensation of UDP-galactose and D-glucose.

Lactose synthase is a two-proteins complex with subunits;  β-galactosyl transferase (a catalytic subunit) and α-lactalbmin (an auxiliary protein). Only the mammary gland expresses the α-lactalbumin that involves in lactose synthesis together with β-galactosyl transferase.

Lactose synthesis pathway

Lactose synthesis pathway in the lumen of Golgi complex in the mammary gland

The next enzyme is Nucleotide diphosphatase (NDPase) which catalyzes the regeneration of Pi from UDP. Nucleotide diphosphatase is a membrane-bound enzyme present in the Golgi complex. Formation of a lactose molecule requires one molecule of glucose and a UDP-galactose both of which come from the cytosol.

In lactose synthesis pathway, GLUT1 transports the glucose into the Golgi lumen by passive transport while UDP-galactose transport happens actively. The pathway is neither influenced by the glucose nor influenced by the product formed (lactose); however, it can be inhibited by the excess of UDP-galactose.

The lactose formed inside the Golgi lumen can’t be transported out of the Golgi vesicles. This is because there is no transporter for lactose and it remains in the lumen of Golgi complex creating an osmotic pressure. To maintain the osmotic pressure water is drained out into the vesicles.

Lactose synthesis stops if there is no α-lactalbumin in the Golgi complex. This is because the β-galactosyl transferase without α-lactalbumin catalyzes the transfer of galactose from UDP-galactose to terminal N-acetylglucosamine of oligosaccharides in glycoproteins biosynthesis in tissues other than mammary glands.

Alternative pathway

There are some alternative lactose synthesis pathways, such as condensation of UDP-galactose and glucose 1-phosphate. The galactosyltransferase catalyzes the condensation of UDP-galactose and glucose-1-phosphate to form lactose-1-phosphate. After that, phosphomonoesterase cleaves the phosphate group (dephosphorylation) from lactose-1-phosphtate giving rise to the lactose. This pathway is present only in some organisms other than mammals.

Utilization of Lactose

Lactase present in the gastrointestinal track can easily hydrolyze the lactose. In the GI tract, lactose breaks down into two hexoses; galactose and glucose. After digestion, villi and microvilli of GI tract absorb the hexoses for further cellular metabolism. Most of the mammals including human undergo a natural decline in lactase level following weaning; a process of gradual replacement of milk with another source of nutrition in the childhood.

However, in the Asian and black group people, lactase level declines during early childhood while in most Caucasians the decline of lactase occurs in late childhood. The lowered production of lactase is a hypolactasia that leads to the incomplete digestion of the lactose. Incomplete digestion of the lactose results in a rise of the osmotic load in the colon after consumption of the milk products that causes diarrhea.

Lactose Utilization In Bacteria

Some bacteria have an alternative mechanism of utilizing lactose as a source of energy. When there is no glucose, they utilize to sustain their life. The mechanism is based on the genetic control; Lac-Operon. Lac-Operon is a set of genes that encodes a series of enzymes for the lactose metabolism. The bacteria express it to synthesize three different enzymes that break down the lactose. Two of them are permease and β-galactosidase. These two are the most important enzymes responsible for the lactose metabolism. Permease provides a channel for the lactose transport while β-galactosidase catalyzes the lactose breakdown into galactose and glucose.

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