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Glycans, a class of complex heterogeneous molecules, can be covalently attached to proteins to form glycosylated proteins that regulate various physiological and pathological processes. Glycosylated proteins or glycoproteins comprise N-linked and O-linked oligosaccharides. O-glycosylation is the most common type of protein glycosylation. Here, glycans attach to the oxygen atom of the hydroxyl groups of Serine or Threonine residues. O-linked glycosylation occurs later in protein processing,...
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[Gla-containing proteins].

Toshio Okano1

  • 1Department of Hygienic Sciences, Kobe Pharmaceutical University, Japan.

Clinical Calcium
|January 30, 2014
PubMed
Summary

Discover the complex roles of gamma-carboxylation in protein function beyond blood coagulation. Research suggests undercarboxylated forms of proteins like osteocalcin regulate glucose metabolism and insulin sensitivity.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Post-Translational Modifications

Context:

  • 16 gamma-carboxyglutamic acid (Gla)-containing proteins identified in humans.
  • 7 Gla proteins are involved in the blood coagulation cascade, while 9 are not.
  • Gamma-carboxylation, catalyzed by gamma-glutamyl carboxylase with vitamin K, modifies glutamic acid residues.

Purpose:

  • To explore the multifaceted roles of gamma-carboxylation in protein function.
  • To investigate mechanisms beyond simple protein activation by gamma-carboxylation.
  • To understand the regulatory functions of undercarboxylated and decarboxylated proteins.

Summary:

  • Gamma-carboxylation is a post-translational modification essential for certain protein functions, notably in blood coagulation.

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  • Contrary to expectations, undercarboxylated osteocalcin, not highly carboxylated osteocalcin, demonstrates regulatory effects on glucose metabolism and insulin sensitivity in mice.
  • This finding indicates that the degree of gamma-carboxylation and potential decarboxylation significantly influence protein activity.

    • Impact:

    • Challenges the traditional view of gamma-carboxylation solely as a protein activation mechanism.
    • Highlights the potential for under- and decarboxylated proteins to play critical regulatory roles in metabolic processes.
    • Opens new avenues for research into the broader physiological functions of Gla-proteins and their modifications.