Structural Biochemistry/Carbohydrates/Oligosaccharides

Oligosaccharide is a carbohydrate polymers comprise three to ten monosaccharides, or, simple sugars. They were linked together mostly by O-glycosidic bond through condensation reaction between an anomeric carbon of a monosaccharide and the other. They can also form N-glycosidic linkages under certain atmosphere. The minimum numbers of reducing sugar components is one molecule lesser than the total number of simple sugars. Reducing sugar can be characterized from the hydroxyl group (-OH group) on the anomeric carbon.

O-glycosidic bond

Use of Oligosaccharides


Numbers of oligosaccharide molecules may form polysaccharides through multiple linkages between the anomeric carbon at the end of a molecule and the hydroxyl groups on another oligosaccharide molecule. Through O-glycosidic linkage and N-glycosidic bond, oligosaccharide may react with lipids and form lipopolysaccharides or saccharolipids. N-linked oligosaccharides can also react with the side chain(s) of amino acid residues - particularly Asparagine from a protein - to form a Glycoprotein. Glycoprotein does not form on random part of proteins. Glycoprotein usually forms on a residue that has sequence of Asn-X-Ser or Asn-X-Thr. However, not all of such residues will be attached to sugar molecule.

They are usually linked due to nitrogen or oxygen bonds to compatible amino acids. Oligosaccharides are known to be found in glycolipids and glycoproteins. Some of them are found from the breakdown of starch and cellulose, they are called cellodextrin and maltodextrin. Chemical marking is one of the functions of oligosaccharides, this is because they have much variations let similarities. For instance,blood types are marked by oligosaccharides. 'A' blood type has one oligosaccharide, 'B' blood type has one too. Both of these oligosaccharide markers are present in 'AB' blood type while 'O' blood type has none.The reason why blood needs to be typed before transfusion is because these oligosaccharides in blood are different enough than each other to be attacked by the body's immune system. Oligosaccharides can be identified as antigens detected by immune systems with incompatible blood as foreign pathogens. If transfusion were to occur with incompatible blood types, clotting and major illnesses would occur ultimately causing death. However, type AB blood contains all the possible oligosaccharide combinations possible (A or B) and since type O blood has no markers attached to it, type AB blood carriers are generally called universal acceptors. Whereas type O blood carriers can only accept blood transfusion from other type O blood donors which do not contain any oligosaccharides present within red blood cells.



Galactooligosaccharides are synthesized through an enzymatic conversion of lactose. It is comprised of chain units of galactose group through consecutive transgalactosylation reactions, which the degree of polymerization ranging from 2 to 8 monomeric units. It is known that these new classes of prebiotics have an important role in improving gut health by sustaining beneficial and balanced gut microbiota. Today, many infant formula companies have galactooligosaccharides in their formula milk.

Human Milk Oligosaccharides


Human milk oligosaccharides are complex glycans that can be found in breast milk. One of the most important factors in infant’s diet is from breast milk, which pertains one of the most complex group of oligosaccharides known as Human milk oligosaccharides(HMOs). They are found in three, four, five, or even six chain sugars. For example, some of the HMOs include raffinose, 2’-fucosyl-lactose, 3’-fucosyl-lactose, 3’-sialyl-lactose, 6’-sialyl-lactose, and Lacto-N-tetraose. These HMOs differ in their size, structure, and specific linkages. There are more than 150 distinct Human Milk Oligosaccharide structures out there that are identified so far. Also, these HMOs are distinct in their structure, acidity, and functions. The backbone of Human Milk Oligosaccharides is the disaccharide lactose, which is formed by the linkage between galactose and glucose sugars. The final structure of HMO all depends on whether the backbone, lactose, is fucosylated or sialated, in either beta or alpha configurations or at a different carbon. For example, 2’-fucosyl-lactose has a fucose group at the alpha-1-3 position of the glucose monosaccharide of the lactose. Being sialated means the addition of a sialic acid group and formation of an acidic HMO.

HMO Formation


When the protein alpha-lactalbumin, also referred to as LALBA, is present, the enzyme beta-1,4-galactosyltransferase changes its function so it connects galactose to glucose sugars, which forms lactose. Human milk oligosaccharides are formed from lactose sugars, but the exact mechanism for this transformation is still unknown. HMOs are produced only when a woman is lactating and are formed in the mammary glands.

HMO Research


Colostrum, which is the liquid secreted by women’s breasts plus or minus several days of childbirth, are known to contain the highest amounts of HMOs, which varies per individual, but falls in the range of 20-30 g per liter. Colostrum contains more amounts of acidic HMOs relative to others. Matured breast milk contains a significantly less amount of approximately 10 g per liter. Therefore, premature newborns are fed breast milk that contains a higher amount of HMOs than would a baby born after 37 weeks of gestation, since the milk has not had the time to mature.

Although many medical professionals believe breast milk is a healthier alternative to feed newborns from HIV positive mothers than formula, recent findings (what sources ?) by call forth a problem. Studies have suggested that the presence of a specific sugar, 3’-sialyllactose, in breast milk has been found to increase the risk of a HIV-negative baby becoming infected with HIV from his or her HIV-positive mother. However, out of approximately 150 various HMOs, 3’-sialyllactose has been the only one to have any negative impact on the baby, while five others were determined to have a positive effect. Newborns who were fed breast milk that contained these five sugars lived longer than those who drank breast milk that did not contain the sugars. With more research on the effects of HMOs on babies, the findings could be applied to formula milk research. Since formula milk contains only small concentrations of complex oligosaccharides, as opposed to HMOs, studies can be conducted to determine if beneficial HMOs can safely be added to formula milk, and have the same positive effect on newborns. Also, women who produce breast milk containing high levels of 3’-sialyllactose can choose to feed their newborn formula, rather than breast milk. Overall, breast milk is the more beneficial choice to feed a newborn, over formula. Studies strongly indicate that HMOs decrease the likelihood of pathogens attacking the respiratory, urogenital, and gastrointestinal tracts of newborns.

Extracting HMOs


HMOs can successfully be isolated from breast milk. First the milk must be pasteurized to kill off any bacteria. Then the milk undergoes centrifugation to separate the expel the lipids from the aqueous phase. Afterwards, proteins can be formed into pellets, and then removed. Finally, the sugars are left, and they can be separated by gel permeation chromatography, which separates the sugars according to their masses. This is an example of size-exclusion chromatography that uses an organic solvent to elute the sugars.

  • Bode, Lars. "Recent Advances on Structure, Metabolism, and Function of Human Milk Oligosaccharides1." Journal of Nutrition 136.8 (2006): 2127-130. Web. 26 Oct. 2012.

  • Engfer, Meike B., Bernd Stahl, Berndt Finke, Guenther Sawatzki, and Hannelore Daniel. "Human Milk Oligosaccharides Are Resistant to Enzymatic Hydrolysis in the Upper Gastrointestinal Tract 1." American Journal of Clinical Nutrition 71.6 (2000): 1589-596. Web. 26 Oct. 2012.