Role of fructose in glycation and cross-linking of proteins

John Douglas Mcpherson, B. H. Shilton, D. J. Walton

Research output: Contribution to journalArticle

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Abstract

Incubation of carbohydrate-free human serum albumin (HSA) with fructose in an aqueous buffer at pH 7.4 resulted in glycation of ε-amino groups of lysyl residues. A recently developed procedure, involving analysis of hexitol amino acids by high-performance liquid chromatography of phenylthiocarbamyl derivatives, was used to show that 85% of the bound hexose was attached to protein via carbon 2 (C-2). The remainder was attached to protein via carbon 1 (C-1). When incubations were conducted with glucose under identical conditions, all the hexose was attached via C-1. Examination of human ocular lens proteins showed that the majority of the covalently bound hexose was connected to ε-amino groups of lysyl residues via C-1; this was attributed mainly to nonenzymatic glucosylation in vivo, which has already been documented. A significant proportion (10-20%) of the bound hexose was connected via C-2. In view of the HSA-hexose incubation results (above), this indicated that the lens proteins had reacted with endogenous fructose; i.e., they had undergone nonenzymatic fructosylation in vivo. The model protein bovine pancreatic ribonuclease A reacted with fructose and glucose at similar rates under physiological conditions. However, covalent, non-disulfide cross-linking, which could be inhibited by D-penicillamine, was induced 10 times more rapidly by fructose than by glucose. It is postulated that some of the protein cross-linking that occurs in vivo is fructose-induced. The possible significance of these processes in diabetic subjects is discussed.

Original languageEnglish (US)
Pages (from-to)1901-1907
Number of pages7
JournalBiochemistry
Volume27
Issue number6
StatePublished - 1988
Externally publishedYes

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Hexoses
Fructose
Pancreatic Ribonuclease
Crystallins
Proteins
Glucose
Serum Albumin
Carbon
Penicillamine
High performance liquid chromatography
Buffers
High Pressure Liquid Chromatography
Carbohydrates
Derivatives
Amino Acids

ASJC Scopus subject areas

  • Biochemistry

Cite this

Mcpherson, J. D., Shilton, B. H., & Walton, D. J. (1988). Role of fructose in glycation and cross-linking of proteins. Biochemistry, 27(6), 1901-1907.

Role of fructose in glycation and cross-linking of proteins. / Mcpherson, John Douglas; Shilton, B. H.; Walton, D. J.

In: Biochemistry, Vol. 27, No. 6, 1988, p. 1901-1907.

Research output: Contribution to journalArticle

Mcpherson, JD, Shilton, BH & Walton, DJ 1988, 'Role of fructose in glycation and cross-linking of proteins', Biochemistry, vol. 27, no. 6, pp. 1901-1907.
Mcpherson, John Douglas ; Shilton, B. H. ; Walton, D. J. / Role of fructose in glycation and cross-linking of proteins. In: Biochemistry. 1988 ; Vol. 27, No. 6. pp. 1901-1907.
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