What enzyme glycosylates collagen?

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From the Guidelines

Vitamin C is essential for the glycosylation of collagen, acting as a cofactor for the enzymes prolyl hydroxylase and lysyl hydroxylase, which are involved in the hydroxylation of proline and lysine residues in collagen 1. The process of collagen glycosylation is crucial for the proper formation and stability of collagen fibrils. The glycosylation of collagen is a post-translational modification that occurs in the endoplasmic reticulum and Golgi apparatus, where enzymes such as hydroxylysyl galactosyltransferase and galactosylhydroxylysyl glucosyltransferase add sugar molecules to specific hydroxylysine residues in the collagen molecule. Some key points to consider about collagen glycosylation include:

  • The importance of vitamin C as a cofactor for the enzymes involved in collagen hydroxylation 1
  • The role of glycosylation in collagen fibril formation and stability
  • The potential for non-enzymatic glycosylation (glycation) to occur in collagen, particularly in disease states such as diabetes
  • The variation in collagen glycosylation by tissue type and the impact of age and disease states on this process. In the context of real-life clinical medicine, ensuring adequate vitamin C intake is crucial to support collagen glycosylation and overall collagen health 1.

From the Research

Glycosylation of Collagen

The glycosylation of collagen is a crucial post-translational modification that involves the attachment of glycan moieties to specific hydroxylysine residues on procollagen alpha chains. This process is essential for collagen and extracellular matrix (ECM) homeostasis 2.

Enzymes Involved in Collagen Glycosylation

Several glycosyltransferase enzymes are involved in the glycosylation of collagen, including:

  • COLGALT1 and COLGALT2, which are associated with the glycosylation of collagens 3
  • LH3, which has lysyl hydroxylase, hydroxylysyl galactosyltransferase, and galactosylhydroxylysyl glucosyltransferase activities 4
  • GLT25D1 and GLT25D2, which are collagen galactosyltransferases that correspond to the GLT25D1 and GLT25D2 proteins 5
  • PGGHG glucosidase, which is involved in the glycosylation of collagens 3

Glycosylation Process

The glycosylation of collagen involves the attachment of galactose and glucose-galactose units to specific hydroxylysine residues on procollagen alpha chains. This process occurs in the endoplasmic reticulum before triple-helix formation and is mediated by beta(1-O)galactosyl- and alpha(1-2)glucosyltransferase enzymes 5. The resulting galactosyl-hydroxylysine (Gal-Hyl) and glucosyl-galactosyl-hydroxylysine (Glc-Gal-Hyl) are essential for collagen and ECM homeostasis 2.

Importance of Collagen Glycosylation

Collagen glycosylation is essential for the formation of basement membranes and the organization of collagen fibrils 4. It is also involved in various biological and pathological processes, including collagen fibrillogenesis, intermolecular cross-linking, and collagen-cell interaction 6.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Glycosylation of Type I Collagen.

Methods in molecular biology (Clifton, N.J.), 2019

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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