Skip to main content
SpringerLink
Log in

Die Bedeutung der Maillard-Reaktion in der menschlichen Physiologie

  • Übersichten
  • Published:
Zeitschrift für Ernährungswissenschaft Aims and scope Submit manuscript

Zusammenfassung

Mehr als 50 Jahre nachdem Maillard (26) die Reaktion von Aminosäuren mit Glucose beschrieben hatte, wurde gefunden, daß diese Reaktion auch unter physiologischen Bedingungen im menschlichen Körper abläuft. Zuerst war entdeckt worden, daß humanes Hämoglobin proteingebundene Amadoriprodukte enthält, die bei Diabetikern mit erhöhten Blutglucosewerten vermehrt waren. Die Bestimmung von fruktosyliertem Hämoglobin ist bereits zur Beurteilung der diabetischen Stoffwechsellage weitverbreitet. Bald darauf wurde nachgewiesen, daß auch andere Proteine wie z.B. Albumin, Linsencrystallin, Proteine der Gerinnungskaskade, Kollagene, Lipoproteine, Zellmembranproteine und andere dieser postribosomalen Modifikation unterliegen, die zu Veränderung von Struktur und Funktion des betreffenden Proteins führen kann. Später wurde erkannt, daß langlebige Proteine altersabhängig braun, fluoreszierend und unlöslich werden. Da diese späten Stadien der Maillardreaktion bei Diabetikern schneller auftreten, wurde vermutet, daß die Maillardreaktion zur Pathophysiologie des Alterns und zur Entstehung der diabetischen Spätschäden beiträgt. Obwohl die ursächliche Beteiligung der Maillardprodukte bei der Entwicklung diabetischer Spätschäden noch nicht verstanden wird, werden bereits klinische Versuche mit dem Medikament Aminoguanidin gemacht, welches die Bildung von späten Maillardprodukten verhindert.

Summary

More than 50 years after Maillard's original paper describing the reaction of amino acids with glucose it was found that this reaction also occurs under physiological conditions in the human body. Initially, it was discovered that human hemoglobin contains protein-bound Amadori-products that are increased in diabetic patients with elevated blood glucose levels. Measurements of fructosylated hemoglobin are now widely used as an index of glycemia in diabetes. It was soon recognized that this postribosomal modification is common to other proteins in vivo like albumin, lens crystallins, proteins of the clotting cascade, collagens, lipoproteins, proteins of the cell membrane, and others. This may lead to alterations in structure and function of the respective protein. Later, the realization that long-lived proteins become browned, fluorescent, and insoluble with age, and at an accelerated rate in diabetes, suggested that later stages of the Maillard reaction might proceed in vivo and contribute to some of the pathophysiology associated with both aging and diabetes. Although the contribution of the Maillard products to the development of diabetic late complications is not fully understood, attempts are being made to prevent formation of late Maillard product with aminoguanidine, a drug currently under clinical testing.

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

Abbreviations

AGE:

advanced glucosylation end products

HPLC:

high pressure liquid chromatography

LDL:

low density lipoprotein

HbA1c :

fruktosyliertes Hämoglobin

Literatur

  1. Ahmed MU, Thorpe SR, Baynes JW (1986) Identification of carboxymethyllysine as a degradation product of fructoselysine in glycated protein. J Biol Chem 261:4889–4994

    CAS  Google Scholar 

  2. Armbruster D (1987) Fructosamine: structure, analysis and clinical usefulness. Clin Chem 33:2153–2163

    CAS  Google Scholar 

  3. Bailey AJ, Kent MJC (1989) In: Baynes, Monnier (eds) The Maillard Reaction in Aging, Diabetes and Nutrition. Alan R Liss Inc, New York, pp 109–122.

    Google Scholar 

  4. Baynes JW, Thorpe SR, Murtiashaw MH (1984) Nonenzymatic glycosylation of lysine residues in albumin. Meth Enzymol 106:88–98

    Article  CAS  Google Scholar 

  5. Brownlee M, Cerami A (1981) The biochemistry of the complications of diabetes mellitus. Ann Rev Biochem 50:385–432

    Article  CAS  Google Scholar 

  6. Brownlee M, Vlassara H, Cerami A (1980) Measurement of glycosylated amino acids and peptides from urine of diabetic patients using affinity chromatography. Diabetes 29:1044–1047

    Article  CAS  Google Scholar 

  7. Brownlee M, Vlassara H, Cerami A (1984) Inhibition of heparincatalyzed human antithrombin III activity by nonenzymatic glycosylation: possible role in fibrin deposition in diabetes. Diabetes 33:532–535

    Article  CAS  Google Scholar 

  8. Brownlee M, Vlassara H, Cerami A (1985) Nonenzymatic glycosylation products on collagen covalently trap low-density-lipoprotein. Diabetes 34:938–941

    Article  CAS  Google Scholar 

  9. Brownlee M, Vlassara H, Kooney A, Ulrich P, Cerami A (1986) Aminoguanidine prevents diabetes induced arterial wall protein cross-linking. Science 232:1629–1632

    Article  CAS  Google Scholar 

  10. Brownlee M, persönliche Mitteilung (1989)

  11. Bunn HF, Shapiro R, McManus MJ, Garrick L, McDonald MJ, Gallop PJ, Gabbay KH (1979) Structural heterogenity of human hemoglobin A due to nonenzymatic glycosylation. J Biol Chem 254:3892–3898

    CAS  Google Scholar 

  12. Chiou SH, Chylack LT Jr, Tung WH, Bunn HF (1981) Nonenzymatic glycosylation of bovine lens crystallins: effect of aging. J Biol Chem 256:5176–5180

    CAS  Google Scholar 

  13. Curtiss LK, Witztum JL (1983) A novel method for generating region-specific monoclonal antibodies to modified proteins. J Clin Invest 72:1427–1438

    Article  CAS  Google Scholar 

  14. Dolhofer R, Wieland OH (1981) Improvement of the thiobarbituric and acid assay for serum glycosylprotein determination. Clin Chim Acta 112:197–204

    Article  CAS  Google Scholar 

  15. Erbersdobler HF, Purwing U, Bossen M, Trautwein E (1985) Proceedings of the 3rd Int. Symposium on the Maillard Reaction “Amino-Carbonyl Reaction in Food and Biological Systems”, Fuji Institute, Japan

    Google Scholar 

  16. Erbersdobler H, Zucker H (1966) Untersuchungen zum Gehalt an Lysin und verfügbarem Lysin in Trockenmagermilch. Milchwiss. 21:564–568

    CAS  Google Scholar 

  17. Finot PA, Bricout J, Viani R, Mauron J (1968) Identification of a new lysine derivative obtained upon acid hydrolysis of heated milk. Experientia 24:1097–1099

    Article  CAS  Google Scholar 

  18. Finot PA, Magnenat E (1981) Metabolic transit of early and advanced Maillard products. Prog Fd Nutr Sci 5:193–207

    CAS  Google Scholar 

  19. Flückiger R, Winterhalter KH (1976) In vitro synthesis of hemoglobin A1c. FEBS Lett. 71:356–360

    Article  Google Scholar 

  20. Garlick RL, Bunn HF, Spiro RG (1988) Nonenzymatic glycation of basement membranes from human glomeruli and bovine sources. Diabetes 37:1144–1150

    Article  CAS  Google Scholar 

  21. Garlick RL, Mazer JS, Chylack LT Jr, Tung WH, Bunn HF (1984) Nonenzymatic glycation of human lens crystallin: effect of aging and diabetes mellitus. J Clin Invest 74:1742–1749

    Article  CAS  Google Scholar 

  22. Hodge JE (1955) The Amadori rearrangement. Adv Carbohydr Chem 10:169–205

    CAS  Google Scholar 

  23. Johnson RN, Metcalf PA, Baker JR (1982) Fructosamine: a new approach to the estimation of serum glycosylprotein. An index of diabetic control. Clin Chim Acta 127:87–95

    Article  Google Scholar 

  24. Ledl F, Schleicher E (1990) Die Maillard-Reaktion in Lebensmitteln und im menschlichen Körper — neue Ergebnisse zu Chemie, Biochemie und Medizin. Angew Chem 102:597–626

    Article  CAS  Google Scholar 

  25. Lutjens A, te Velde AA, van der Veen EA, Meer JVD (1985) Glycosylation of human fibrinogen in vivo. Diabetologia 28:87–89

    Article  CAS  Google Scholar 

  26. Maillard LC (1912) Action des acides aminés sur les sucres; formation des mélanoidines par voie méthodique. CR Acad Sci 154:66–68

    CAS  Google Scholar 

  27. Monnier VM, Kohn RR, Cerami A (1984) Accelerated age-related browning of human collagen in diabetes mellitus. Proc Natl Acad Sci USA 81:583–587

    Article  CAS  Google Scholar 

  28. Neglia Cl, Cohen HJ, Garber AR, Ellis PD, Thorpe SR, Baynes JW (1983)13C-NMR investigation of nonenzymatic glucosylation of protein: model studies using RNase A. J Biol Chem 258:14279–14283

    CAS  Google Scholar 

  29. Oimoni M, Nishimoto S, Kitamura Y, Matsumoto S, Hatanaka H, Ishikawa K, Baba S (1985) Increased fructose-lysine of hair protein in diabetic patients. Klin Wochenschr 63:728–730

    Article  Google Scholar 

  30. Rahbar S, Blumenfeld O, Ranney HM (1969) Studies of an unusual hemoglobin in patients with diabetes mellitus. Biochem Biophys Res Comm 36:838–843

    Article  CAS  Google Scholar 

  31. Rosenbloom AL, Silberstein JH, Lecotte DC, Richardson K, McCallum M (1981) Limited joint mobility in childhood diabetes mellitus indicates increased risk for microvascular disease. New Engl J Med 305:191–194

    Article  CAS  Google Scholar 

  32. Schleicher E (1986) Nichtenzymatische Glucosylierung von menschlichen Proteinen: analytische, diagnostische und funktionelle Aspekte. Habilitationsschrift: Technische Universität München

    Google Scholar 

  33. Schleicher E, Deufel T, Wieland OH (1981) Nonenzymatic glycosylation of human serum lipoproteins. FEBS Lett 129:1–4

    Article  CAS  Google Scholar 

  34. Schleicher E, Olgemöller B, Schön J, Duürst T, Wieland OH (1985) Limited nonenzymatic glucosylation of low-density lipoprotein does not alter its catabolism in tissue culture. Biochim Biophys Acta 846:226–233

    Article  CAS  Google Scholar 

  35. Schleicher E, Scheller L, Wieland OH (1981) Quantitation of lysine-bound glucose of normal and diabetic erythrocyte membrane by HPLC analysis of furosine. Biochem Biophys Res Comm 99:1011–1019

    Article  CAS  Google Scholar 

  36. Schleicher E, Wieland OH (1981) Specific quantitation by HPLC of protein (lysine) bound glucose in human serum albumin and other glycosylated proteins. J Clin Chem Clin Biochem 19:81–87

    CAS  Google Scholar 

  37. Schleicher E, Wieland OH (1986) Kinetic analysis of glycation as a tool for assessing the half-life of proteins. Biochim Biophys Acta 884:199–205

    Article  CAS  Google Scholar 

  38. Schleicher E, Wieland OH (1989) Proteinglycation: Measurement and clinical relevance. J Clin Chem Clin Biochem 27:557:587

    Google Scholar 

  39. Sell DR, Monnier VM (1990) End-stage renal disease and diabetes catalyze the formation of a pentose derived crosslink from aging human collagen. J Clin Invest 85:380:384

    Article  CAS  Google Scholar 

  40. Shaklai N, Garlick RL, Bunn HF (1984) Nonenzymatic glycosylation of human serum albumin alters its conformation and function. J Biol Chem 259:3812–3817

    CAS  Google Scholar 

  41. Shapiro R, McManus MJ, Zalut C, Bunn HF (1980) Sites of nonenzymatic glycosylation of human hemoglobin A. J Biol Chem 255:3120–3127

    CAS  Google Scholar 

  42. Steinbrecher UP, Witztum JL (1984) Glucosylation of low density lipoproteins to an extent comparable to that seen in diabetes slows their catabolism. Diabetes 33:130–134

    Article  CAS  Google Scholar 

  43. Tarsio JF, Widness B, Rhode TD, Rupp WM, Buchwald H, Furcht LT (1985) Nonenzymatic glycation of fibronectin and alterations in the molecular association of cell matrix and basement membrane components in diabetes mellitus. Diabetes 34:477–484

    Article  CAS  Google Scholar 

  44. Vlassara H, Brownlee M, Cerami A (1986) Novel macrophage receptor for glucose-modified proteins is distinct from previously described scavenger receptor. J Exp Med 164:1301–1309

    Article  CAS  Google Scholar 

  45. Vogt B, Schleicher E, Wieland OH (1982) ɛ-Aminolysine-bound glucose in human tissues obtained at autopsy. Diabetes 31:1123–1127

    Article  CAS  Google Scholar 

  46. Watkins NG, Thorpe SR, Baynes JW (1985) Glycation of amino groups in protein: studies on the specificity of modification of RNase A by glucose. J Biol Chem 260:10 629–10 636

    CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Institute für Klinische Chemie und Diabetesforschung, Krankenhaus München-Schwabing, München

    E. Schleicher

Authors
  1. E. Schleicher
    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

Schleicher, E. Die Bedeutung der Maillard-Reaktion in der menschlichen Physiologie. Z Ernährungswiss 30, 18–28 (1991). https://doi.org/10.1007/BF01910729

Download citation

  • Received:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF01910729

Schlüsselwörter

Key words

Search

Navigation