Skip to main content

Advertisement

SpringerLink
Log in

Site specificity of glycation and carboxymethylation of bovine serum albumin by fructose

  • Published:
Amino Acids Aims and scope Submit manuscript

Summary.

We report an investigation of the site specificity, extent and nature of modification of bovine serum albumin (BSA) incubated with fructose or glucose at physiological temperature and pH. Sites of early glycation (Heyns rearrangement products (HRP) from fructose; fructoselysine (FL) from glucose) as well as advanced glycation (N ε-(carboxymethyl)lysine; CML) were analyzed by liquid chromatography-mass spectrometry. The major site of modification by fructose, like glucose, is Lysine-524 and this results in, respectively, 31 and 76% loss of the corresponding unmodified tryptic peptide, Gln525-Lys533. In addition, total lysine, HRP, FL, CML and N ε-(carboxyethyl)lysine in the incubations, was quantified. Almost all of the loss of lysine in the fructose-modified BSA was attributed to the formation of CML, with the yield of CML being up to 17-fold higher than glucose-modified BSA. A mechanism for the formation of CML from the HRP is proposed.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • MU Ahmed SR Thorpe JW Baynes (1986) ArticleTitleIdentification of N-epsilon-(carboxymethyl)lysine as a degradation product of fructoselysine in glycated protein J Biol Chem 261 4889–4894 Occurrence Handle3082871 Occurrence Handle1:CAS:528:DyaL28Xkt1anu74%3D

    PubMed  CAS  Google Scholar 

  • MU Ahmed E Brinkmann-Frye TP Degenhardt SR Thorpe JW Baynes (1997) ArticleTitleNε-(Carboxyethyl)lysine, a product of the chemical modification of proteins by methylglyoxal, increases with age in humen lens proteins Biochem J 324 565–570 Occurrence Handle9182719 Occurrence Handle1:CAS:528:DyaK2sXjvFGmtLc%3D

    PubMed  CAS  Google Scholar 

  • MAM van Boekel HJ Hoenders (1992) ArticleTitleGlycation of crystallins in lenes from aging and diabetic individuals FEBS Lett 314 1–4 Occurrence Handle1451795 Occurrence Handle1:CAS:528:DyaK3sXjslSgsg%3D%3D Occurrence Handle10.1016/0014-5793(92)81446-S

    Article  PubMed  CAS  Google Scholar 

  • JWC Brock DJS Hinton WE Cotham TO Metz SR Thorpe JW Baynes JM Ames (2003) ArticleTitleProteomic analysis of the site specificity of glycation and carboxymethylation of ribonuclease J Proteome Res 2 506–513 Occurrence Handle14582647 Occurrence Handle1:CAS:528:DC%2BD3sXkvFyjs7k%3D Occurrence Handle10.1021/pr0340173

    Article  PubMed  CAS  Google Scholar 

  • EB Casey HR Zhao EC Abraham (1995) ArticleTitleRole of glycine 1 and Lysine 2 in the glycation of bovine γB-crystallin J Biol Chem 270 20781–20786 Occurrence Handle7657661 Occurrence Handle1:CAS:528:DyaK2MXnvVOqu78%3D Occurrence Handle10.1074/jbc.270.39.23119

    Article  PubMed  CAS  Google Scholar 

  • MP Cohen (2003) ArticleTitleIntervention strategies to prevent pathogenic effects of glycated albumin Arch Biochem Biophys 419 25–30 Occurrence Handle14568005 Occurrence Handle1:CAS:528:DC%2BD3sXotVCjur8%3D Occurrence Handle10.1016/j.abb.2003.08.012

    Article  PubMed  CAS  Google Scholar 

  • WE Cotham TO Metz PL Ferguson JWC Brock DJS Hinton SR Thorpe JW Baynes JM Ames (2004) ArticleTitleProteomic analysis of arginine adducts on glyoxal-modified ribonuclease Mol Cell Proteomics 3 1145–1153 Occurrence Handle15377717 Occurrence Handle1:CAS:528:DC%2BD2MXhvFarsQ%3D%3D Occurrence Handle10.1074/mcp.M400002-MCP200

    Article  PubMed  CAS  Google Scholar 

  • JA Dunn JS Patrick SR Thorpe JW Baynes (1989) ArticleTitleOxidation of glycated proteins: age-dependent accumulation of Nε-(carboxymethyl)lysine in lens proteins Biochemistry 28 9464–9468 Occurrence Handle2514802 Occurrence Handle1:CAS:528:DyaL1MXmt12ls7k%3D Occurrence Handle10.1021/bi00450a033

    Article  PubMed  CAS  Google Scholar 

  • JA Dunn DR McCance SR Thorpe TJ Lyons JW Baynes (1991) ArticleTitleAge-dependent accumulation of Nε-(carboxymethyl)lysine and Nε-(carboxymethyl)hydroxylysine in human skin collagen Biochemistry 30 1205–1210 Occurrence Handle1899338 Occurrence Handle1:CAS:528:DyaK3MXlvFCmug%3D%3D Occurrence Handle10.1021/bi00219a007

    Article  PubMed  CAS  Google Scholar 

  • KH Gabbay JH Kinoshita (1972) ArticleTitleMechanism of development and possible prevention of sugar cataracts Isr J Med Sci 8 1557–1561 Occurrence Handle4647820 Occurrence Handle1:CAS:528:DyaE3sXisFem

    PubMed  CAS  Google Scholar 

  • RL Garlick JS Mazer (1983) ArticleTitleThe principal site of nonenzymatic glycosylation of human serum albumin in vivo J Biol Chem 258 6142–6146 Occurrence Handle6853480 Occurrence Handle1:CAS:528:DyaL3sXktlCksrY%3D

    PubMed  CAS  Google Scholar 

  • MA Glomb VM Monnier (1995) ArticleTitleMechanism of protein modification by glyoxal and glycoaldehyde, reactive intermediates of the Maillard reaction J Biol Chem 270 10017–10026 Occurrence Handle7730303 Occurrence Handle1:CAS:528:DyaK2MXltlWnsrY%3D Occurrence Handle10.1074/jbc.270.17.10017

    Article  PubMed  CAS  Google Scholar 

  • DJ Heaf DJ Galton (1975) ArticleTitleSorbitol and other polyols in lens, adipose tissue and urine in diabetes mellitus Clin Chim Acta 63 41–47 Occurrence Handle1181073 Occurrence Handle1:STN:280:DyaE28%2Fkt1ehsA%3D%3D Occurrence Handle10.1016/0009-8981(75)90376-9

    Article  PubMed  CAS  Google Scholar 

  • HG Hers (1956) ArticleTitleLe mécanisme de la transformation de glucose en fructose par les vésicules séminales Biochim Biophys Acta 22 202–203 Occurrence Handle13373872 Occurrence Handle1:CAS:528:DyaG2sXhsVWrug%3D%3D Occurrence Handle10.1016/0006-3002(56)90247-5

    Article  PubMed  CAS  Google Scholar 

  • K Heyns G Müller H Paulsen (1967) ArticleTitleQuantitative investigation of the reaction of hexoses with amino acids Justus Liebigs Ann Chem 703 202–214 Occurrence Handle5593875 Occurrence Handle1:CAS:528:DyaF2sXkvFWisr4%3D

    PubMed  CAS  Google Scholar 

  • N Iberg R Flückinger (1986) ArticleTitleNonenzymic glycosylation of albumin in vivo: Identification of multiple glycosylation sites J Biol Chem 261 13542–13545 Occurrence Handle3759977 Occurrence Handle1:CAS:528:DyaL28XlvVKhsL0%3D

    PubMed  CAS  Google Scholar 

  • JA Jedziniak LT Chylack SuffixJr HM Cheng MK Gillis AA Kalustian WH Tung (1981) ArticleTitleThe sorbitol pathway in the human lens: aldose reductase and polyol dehydrogenase Invest Ophthalmol Vis Sci 20 314–326 Occurrence Handle6782033 Occurrence Handle1:CAS:528:DyaL3MXkslOlt7Y%3D

    PubMed  CAS  Google Scholar 

  • A Lapolla D Fedele R Reitano NC Aricò R Seraglia P Traldi E Marotta R Tonani (2004) ArticleTitleEnzymatic digestion and mass spectrometry in the study of advanced glycation end products/peptides Am J Mass Spectrom 15 496–509 Occurrence Handle1:CAS:528:DC%2BD2cXisVGhurs%3D Occurrence Handle10.1016/j.jasms.2003.11.014

    Article  CAS  Google Scholar 

  • J Leonil D Molle J Fauquant JL Maubois RJ Pearce S Bouhallab (1997) ArticleTitleCharacterization by ionisation mass spectrometry of lactosyl β-lactoglobulin conjugates formed during heat treatment of milk and whey and identification of one lactose-binding site J Dairy Sci 80 2270–2281 Occurrence Handle9361199 Occurrence Handle1:CAS:528:DyaK2sXntFems74%3D Occurrence Handle10.3168/jds.S0022-0302(97)76176-9

    Article  PubMed  CAS  Google Scholar 

  • I Macdonald A Keyser D Pacy (1978) ArticleTitleSome effects in man, of varying the load of glucose, sucrose, fructose or sorbitol on metabolites in blood Am J Clin Nutr 31 1305–1311 Occurrence Handle677070 Occurrence Handle1:CAS:528:DyaE1cXlsVGmsb0%3D

    PubMed  CAS  Google Scholar 

  • H Makino K Shikata M Kushiro K Hironaka Y Yamasaki H Sugimoto Z Ota N Araki S Horiuchi (1996) ArticleTitleRoles of advanced glycation end-products in the progression of diabetic nephropathy Nephrol Dial Transpl 11 76–80 Occurrence Handle1:CAS:528:DyaK2sXhsFCitbc%3D

    CAS  Google Scholar 

  • E Marotta A Lapolla D Fedele A Senesi R Reitano M Witt R Seraglia P Traldi (2003) ArticleTitleAccurate mass measurements by Fourier transform mass spectrometry in the study of advanced glycation end products/peptides J Mass Spectrom 38 196–205 Occurrence Handle12577286 Occurrence Handle1:CAS:528:DC%2BD3sXhsFGmurk%3D Occurrence Handle10.1002/jms.431

    Article  PubMed  CAS  Google Scholar 

  • JD McPherson BH Shilton DJ Walton (1988) ArticleTitleRole of fructose in glycation and cross-linking of proteins Biochemistry 27 1901–1907 Occurrence Handle3132203 Occurrence Handle1:CAS:528:DyaL1cXht1Kqurs%3D Occurrence Handle10.1021/bi00406a016

    Article  PubMed  CAS  Google Scholar 

  • Y Nakamura Y Horii T Nishino H Shiiki Y Sakaguchi T Kagoshima K Dohi Z Makita H Vlassara R Bucula (1993) ArticleTitleImmunohistochemical localization of advanced glycosylation endproducts in coronary atheroma and cardiac tissue in diabetes-mellitus Am J Pathol 143 1649–1656 Occurrence Handle8256853 Occurrence Handle1:STN:280:DyaK2c%2FnvFSnsA%3D%3D

    PubMed  CAS  Google Scholar 

  • BJ Ortwerth SH Slight M Prabhakaram Y Sun JB Smith (1992) ArticleTitleSite-specific glycation of lens crystallins by ascorbic acid Biochim Biophys Acta 1117 207–215 Occurrence Handle1525182 Occurrence Handle1:CAS:528:DyaK38XmtlWmsL4%3D

    PubMed  CAS  Google Scholar 

  • P Pam SA McLuckey (2003) ArticleTitleElectrospray ionization of protein mixtures at low pH Anal Chem 75 1491–1499 Occurrence Handle10.1021/ac020637w Occurrence Handle1:CAS:528:DC%2BD3sXht1SgsLo%3D

    Article  CAS  Google Scholar 

  • J Pennington JJ Harding (1994) ArticleTitleIdentification of the site of glycation of γ-II-crystallin by (14C)-fructose Biochim Biophys Acta 1226 163–167 Occurrence Handle8204663 Occurrence Handle1:CAS:528:DyaK2cXktlagur0%3D

    PubMed  CAS  Google Scholar 

  • S Reddy J Bichler KJ Wells-Knecht SR Thorpe J Baynes (1995) ArticleTitleN-Epsilon-(carboxymethyl)lysine is a dominant advanced glycation endproduct (AGE) antigen in tissue proteins Biochemistry 34 10872–10878 Occurrence Handle7662668 Occurrence Handle1:CAS:528:DyaK2MXnsVKrtbY%3D Occurrence Handle10.1021/bi00034a021

    Article  PubMed  CAS  Google Scholar 

  • A Ruttkat HF Ebersdobler (1995) ArticleTitleNε-Carboxymethyllysine is formed during heating of lysine with ketoses J Sci Food Agric 68 261–263 Occurrence Handle1:CAS:528:DyaK2MXmt12msLc%3D

    CAS  Google Scholar 

  • M Sakai M Oimomi M Kasuga (2002) ArticleTitleExperimental studies on the role of fructose in the development of diabetic complications Kobe J Med Sci 48 125–136 Occurrence Handle12594356 Occurrence Handle1:CAS:528:DC%2BD3sXmtVClu7o%3D

    PubMed  CAS  Google Scholar 

  • P Saxena AK Saxena XL Cui M Obenovich K Gudipaty VM Monnier (2000) ArticleTitleTransition metal-catalyzed oxidation of ascorbate in human cataract extracts: possible role of advanced glycation end products Invest Opthalmol Vis Sci 41 1473–1481 Occurrence Handle1:STN:280:DC%2BD3c3ls1GhsQ%3D%3D

    CAS  Google Scholar 

  • DB Shin F Hayase H Kato (1988) ArticleTitlePolymerization of proteins caused by reaction with sugars and the formation of 3-deoxyglucosone under physiological conditions Agric Biol Chem 52 1451–1458 Occurrence Handle1:CAS:528:DyaL1cXltVKlsLg%3D

    CAS  Google Scholar 

  • MA Smith S Taneda PL Richey S Miyata S-D Yan D Stern LM Sayre VM Monnier G Perry (1994) ArticleTitleAdvanced Maillard reaction end products are associated with Alzheimer’s disease pathology Proc Natl Acad Sci USA 91 5710–5714 Occurrence Handle8202552 Occurrence Handle1:CAS:528:DyaK2cXksFGisb4%3D Occurrence Handle10.1073/pnas.91.12.5710

    Article  PubMed  CAS  Google Scholar 

  • G Suarez R Rajaram AL Oronsky MA Gawinowicz (1989) ArticleTitleNonenzymic glycation of bovine serum albumin by fructose (fructation). Comparison with the Maillard reaction initiated by glucose J Biol Chem 264 3674–3679 Occurrence Handle2537288 Occurrence Handle1:CAS:528:DyaL1MXhsFSisrY%3D

    PubMed  CAS  Google Scholar 

  • PJ Thornalley A Langborg HS Minhas (1999) ArticleTitleFormation of glyoxal, methylglyoxal and 3-deoxyglucosone in the glycation of proteins by glucose Biochem J 344 109–116 Occurrence Handle10548540 Occurrence Handle1:CAS:528:DyaK1MXns1yjtrY%3D Occurrence Handle10.1042/0264-6021:3440109

    Article  PubMed  CAS  Google Scholar 

  • JV Valencia SC Weldon D Quinn GH Kiers J DeGroot JM TeKoppele TE Hughes (2004) ArticleTitleAdvanced glycation end product ligands for the receptor for advanced glycation end products: biochemical characterization and formation kinetics Anal Biochem 324 68–78 Occurrence Handle14654047 Occurrence Handle1:CAS:528:DC%2BD3sXptl2qt74%3D Occurrence Handle10.1016/j.ab.2003.09.013

    Article  PubMed  CAS  Google Scholar 

  • MC Wells-Knecht SR Thorpe JW Baynes (1995) ArticleTitlePathways of formation of glycoxidation products during glycation of collagen Biochemistry 34 15134–15141 Occurrence Handle7578127 Occurrence Handle1:CAS:528:DyaK2MXovFOju7o%3D Occurrence Handle10.1021/bi00046a020

    Article  PubMed  CAS  Google Scholar 

  • FK Yeboah I Alli VA Yaylayan (1999) ArticleTitleReactivities of D-glucose and D-fructose during glycation of bovine serum albumin J Agric Food Chem 47 3164–3172 Occurrence Handle10552625 Occurrence Handle1:CAS:528:DyaK1MXksFGhsrw%3D Occurrence Handle10.1021/jf981289v

    Article  PubMed  CAS  Google Scholar 

  • HR Zhao JB Smith XY Jiang EC Abraham (1996) ArticleTitleSites of glycation of beta B-2-crystallin by glucose and fructose Biochem Biophys Res Commun 229 128–133 Occurrence Handle8954094 Occurrence Handle1:CAS:528:DyaK28Xnt12rsb8%3D Occurrence Handle10.1006/bbrc.1996.1768

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Hugh Sinclair Unit of Human Nutrition, School of Food Biosciences, University of Reading, Whiteknights, U.K.

    D. J. S. Hinton

  2. School of Biological and Food Sciences, Queen’s University Belfast, Belfast, Northern Ireland

    J. M. Ames

Authors
  1. D. J. S. Hinton
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. J. M. Ames
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Hinton, D., Ames, J. Site specificity of glycation and carboxymethylation of bovine serum albumin by fructose. Amino Acids 30, 425–434 (2006). https://doi.org/10.1007/s00726-006-0269-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00726-006-0269-2

Search

Navigation