The composition and dynamic nature of the N-linked glycoprofile of bovine milk serum and its individual proteins: A structural and functional analysis

Rivca Valk-Weeber

Research output: ThesisThesis fully internal (DIV)

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Abstract

Bovine milk serum (whey), the solvent that remains after removal of the caseins, contains many functional proteins. Some of these proteins are decorated with carbohydrate structures, also known as glycans, that provide additional functions to their respective proteins. In this work, methods were developed and used for the analysis of the glycosylated proteins of bovine milk whey. The 3 main proteins that contribute to the overall glycoprofile of bovine whey were identified as lactoferrin, immunoglobulin G and glycosylation dependent adhesion molecule 1 (GlyCAM-1). The profile of glycans expressed on the glycoproteins is strongly regulated, but under certain conditions changes can take place. For example, we observed that the glycans of lactoferrin vary during the short colostrum period. In functional studies with highly purified glycans of lactoferrin, we showed that these glycans interact with the immune system via so-called Toll-like receptors. Changes in the glycoprofile can affect the receptor interaction, resulting in altered functionality. The protein GlyCAM-1 is absent in human milk, but in bovine milk we found that its concentration is relatively high. The glycans of GlyCAM-1 make a significant contribution to the overall whey glycoprofile and carry important functional epitopes, with a relatively high sialylation and fucosylation degree. We discovered that the levels of sialylation and fucosylation of GlyCAM-1 vary between individual cows, but also with dietary substrates, potentially as a result of metabolic imbalances. The large contribution of GlyCAM-1 to the overall glycoprofile, together with its glycoprofile variability, makes it an interesting target for further study.
Original languageEnglish
QualificationDoctor of Philosophy
Awarding Institution
  • University of Groningen
Supervisors/Advisors
  • Dijkhuizen, Lubbert, Supervisor
  • de Vos, Paul, Supervisor
  • Leeuwen, van, Sander, Co-supervisor
  • Wuhrer, Manfred, Assessment committee, External person
  • van de Merbel, Nico C., Assessment committee, External person
  • Hettinga, Kasper A., Assessment committee, External person
Award date9-Oct-2020
Place of Publication[Groningen]
Publisher
DOIs
Publication statusPublished - 2020

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