Galactose: definition, foods, metabolism, myelin

What is galactose?

Galactose
Fig. 1 – beta-D-Galactopyranose

Galactose, sometimes abbreviated Gal, is a monosaccharide and the C4 epimer of glucose, that is, they differ only for the position of the -OH group on C4 (axial in Gal, equatorial in glucose).
It has a sweetness equal to 33% of sucrose.

Food sources of galactose

In human nutrition the most part comes from the hydrolysis of the disaccharide lactose, the milk sugar, including that of the human milk.
As mother’s milk is the only source of energy and carbohydrates for newborn, galactose has a crucial role in human nutrition.
The monosaccharide is also bound to caseins, and therefore it is found in all dairy products.
Findings from studies conducted since the 50s of last century have shown that galactose is present not only in milk and dairy products, but also in plant products such as legumes, grains, nuts, tubers and vegetables. It seems that in these foods it is often engaged in bonds resistant to the attack of human digestive enzymes, and therefore not metabolizable. However, different fruits and vegetables contain it also in free form, in variable amounts:

  • less than 0.1 mg/100 g of edible portion: artichokes, mushrooms, olives, and peanuts;
  • more than 10 mg/100 g of edible portion: bell peppers, date, papaya, watermelon, tomato;
  • up to 35.4 mg/100 g of edible portion in persimmon.

These values are very low, but to take into account in case of galactosemia (see below).

Galactose metabolism

Lactose hydrolysis by intestinal lactase leads to Gal release, together a glucose molecule. It is a β-(1→4)-glycosidic reaction. Lactase activity is present in a multifunctional enzyme containing also an active site capable of hydrolyzing milk glycolipids (ceramides to yield fatty acids and sphingosine).
Also bacterial β-galactosidase in yogurt is able to convert milk sugar into its  constituent  monosaccharides.
Free galactose is then absorbed through the mucosa of the small intestine, passes into the portal circulation and is transported to the liver, where it is almost completely absorbed, so that its blood concentration does not exceed 1 mmol/L. It should be noted that glucose represents over 95% of hexoses found in the blood stream.
Under normal physiological conditions one can observe an increase in its blood concentration as a result of alcohol consumption, which reduces its intestinal absorption but also the subsequent hepatic metabolism.

Leloir pathway

Galactose
Fig. 2 – Leloir Pathway

In hepatocytes, galactose enters the Leloir pathway.
Freed from lactose, the monosaccharide is mostly present as beta-isomer, and the first step of its hepatic metabolism is the conversion to the alpha-isomer, in the reaction catalyzed by galactose mutarotase (also known as aldose 1-epimerase).
In the second step, phosphorylation occurs of alpha-D-Gal to Gal-1-phosphate, in the reaction catalyzed by glucokinase (phosphorylation at C-1).
In the next step, galactose-1-phosphate uridyltransferase (GALT) catalyzes the transfer of a UMD group from UDP-Gal to glucose-1-phosphate, with formation of glucose-1-phosphate and UDP-Gal.
The cycle ends when the UDP-Gal is converted to UDP-glucose in the reaction catalyzed by UDP-galactose 4-epimerase (GALE).

Although in theory the glucose-1-phosphate product may be converted into glucose-6-phosphate in the reaction catalyzed by phosphoglucomutase, and then enter the glycolytic pathway, it seems that only a small part of the ingested galactose follows this pathway. Conversely, glucose-1-phosphate, activated to UDP-glucose, is used for glycogen synthesis.

Metabolic fate of UDP-Gal

  • UDP-Gal is an important precursor in the synthesis of glycolipids, such as gangliosides and galactocerebrosides, sphingolipids, mucopolysaccharides, and membrane glycoproteins.
  • In the adult mammary gland, under the influence of prolactin, UDP-Gal can be joined to glucose to give milk sugar.

Galactosemia

Mutations in three of the four enzymes of the Leloir pathway, i.e. galactokinase, GALT or GALE, that cause their malfunction, lead to galactosemia, a pathological condition less frequent but more severe than lactose intolerance.
In the disease, there is an increase in the blood concentration of galactose to values higher than 1 mmol/L; different tissues remove it from the blood stream and reduce it to galactitol (dulcitol) in the reaction catalyzed by aldehyde reductase. Galactitol is not further metabolized, accumulates in tissues and causes pathological changes resulting from the increase in osmotic pressure caused by it.

Galactose and myelin

Myelin is the covering sheath of axons of neurons, where it plays an insulating and protective role, crucial for the conduction of nerve impulses. Lipids account for about 70-80% of the dry weight of myelin, proteins 20-30%. In lipid fraction, in addition to cholesterol and phosphoglycerides, galactocerebrosides are also found.
The participation in the formation of the myelin sheath of nerve fibers, that begins during fetal life and is completed at second childhood, is by far the most important function of galactose.

References

Thoden J.B., Timson D.J., Reece R.J., and M. Holden H.M. Molecular structure of human galactose mutarotase. J Biol Chem 2004;279(22):23431-7 [Abstract]

Nelson D.L., Cox M.M. Lehninger: principles of biochemistry. Fourth edition. 2004 

Rosenthal M.D., Glew R.H. Medical biochemistry: human metabolism in health and disease. A John Wiley & sons, Inc., Publication. 2009

Gross K. C., Acosta P. B. Fruits and vegetables are a source of galactose: implications in planning the diets of patients with Galactosaemia. J Inherit Metab Dis 1991;14(2):253-8 [Abstract]

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