Inactivation of cellular enzymes by carbonyls and protein-bound glycation/glycoxidation products

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Inactivation of cellular enzymes by carbonyls and protein-bound glycation/glycoxidation products. / Morgan, Philip E; Dean, Roger T; Davies, Michael Jonathan.

In: Archives of Biochemistry and Biophysics, Vol. 403, No. 2, 15.07.2002, p. 259-69.

Research output: Contribution to journalJournal articleResearchpeer-review

Harvard

Morgan, PE, Dean, RT & Davies, MJ 2002, 'Inactivation of cellular enzymes by carbonyls and protein-bound glycation/glycoxidation products', Archives of Biochemistry and Biophysics, vol. 403, no. 2, pp. 259-69.

APA

Morgan, P. E., Dean, R. T., & Davies, M. J. (2002). Inactivation of cellular enzymes by carbonyls and protein-bound glycation/glycoxidation products. Archives of Biochemistry and Biophysics, 403(2), 259-69.

Vancouver

Morgan PE, Dean RT, Davies MJ. Inactivation of cellular enzymes by carbonyls and protein-bound glycation/glycoxidation products. Archives of Biochemistry and Biophysics. 2002 Jul 15;403(2):259-69.

Author

Morgan, Philip E ; Dean, Roger T ; Davies, Michael Jonathan. / Inactivation of cellular enzymes by carbonyls and protein-bound glycation/glycoxidation products. In: Archives of Biochemistry and Biophysics. 2002 ; Vol. 403, No. 2. pp. 259-69.

Bibtex

@article{09b95e3c2e61419fb96c65bb3f307dfa,
title = "Inactivation of cellular enzymes by carbonyls and protein-bound glycation/glycoxidation products",
abstract = "Diabetic plasma contains elevated levels of glucose and various low-molecular-weight carbonyl compounds derived from the metabolism of glucose and related materials. These compounds react with protein side chains (Arg, Lys, Cys, and His) to give glycated materials and advanced glycation end products. In this study, we have examined the effect of glucose and carbonyl compounds (methylglyoxal, glyoxal, glycolaldehyde, and hydroxyacetone), and glycation products arising from reaction of these materials with model proteins, on the activity of three key cellular enzymes: glyceraldehyde-3-phosphate dehydrogenase (GAPDH), glutathione reductase, and lactate dehydrogenase, both in isolation and in cell lysates. In contrast to glucose (1M, both fresh and aged for 8 weeks), which had no effect, marked inhibition of all three enzymes was observed with methylglyoxal and glyoxal. GAPDH was also inhibited by glycolaldehyde and hydroxyacetone. Incubation of these enzymes with proteins that had been preglycated with methylglyoxal, but not glucose, also resulted in significant time- and concentration-dependent inhibition with both isolated enzymes and cell lysates. This inhibition was not metal ion, oxygen, superoxide dismutase, or catalase dependent, suggesting that inhibition is not radical mediated. These effects are suggested to be due to direct adduction of the free- or protein-bound carbonyls with the target enzyme. Such an interpretation is supported by the detection of the loss of thiol groups on GAPDH and the detection of cross-linked materials on protein gels. Though direct comparison of the extent of inhibition induced by free versus protein-bound carbonyls was not possible, the significantly higher concentrations of the latter materials over the former in diabetic plasma and cells lead us to suggest that alterations in the activity of key cellular enzymes induced by glycated proteins may play a significant role in the development of diabetic complications.",
keywords = "Acetaldehyde, Acetone, Aldehydes, Animals, Cells, Cultured, Enzyme Activation, Enzymes, Glucose, Glutathione Reductase, Glyceraldehyde 3-Phosphate Dehydrogenase (NADP+), Glycosylation End Products, Advanced, Glyoxal, L-Lactate Dehydrogenase, Mice, Molecular Weight, Proteins, Pyruvaldehyde, Sulfhydryl Compounds",
author = "Morgan, {Philip E} and Dean, {Roger T} and Davies, {Michael Jonathan}",
year = "2002",
month = "7",
day = "15",
language = "English",
volume = "403",
pages = "259--69",
journal = "Archives of Biochemistry and Biophysics",
issn = "0003-9861",
publisher = "Academic Press",
number = "2",

}

RIS

TY - JOUR

T1 - Inactivation of cellular enzymes by carbonyls and protein-bound glycation/glycoxidation products

AU - Morgan, Philip E

AU - Dean, Roger T

AU - Davies, Michael Jonathan

PY - 2002/7/15

Y1 - 2002/7/15

N2 - Diabetic plasma contains elevated levels of glucose and various low-molecular-weight carbonyl compounds derived from the metabolism of glucose and related materials. These compounds react with protein side chains (Arg, Lys, Cys, and His) to give glycated materials and advanced glycation end products. In this study, we have examined the effect of glucose and carbonyl compounds (methylglyoxal, glyoxal, glycolaldehyde, and hydroxyacetone), and glycation products arising from reaction of these materials with model proteins, on the activity of three key cellular enzymes: glyceraldehyde-3-phosphate dehydrogenase (GAPDH), glutathione reductase, and lactate dehydrogenase, both in isolation and in cell lysates. In contrast to glucose (1M, both fresh and aged for 8 weeks), which had no effect, marked inhibition of all three enzymes was observed with methylglyoxal and glyoxal. GAPDH was also inhibited by glycolaldehyde and hydroxyacetone. Incubation of these enzymes with proteins that had been preglycated with methylglyoxal, but not glucose, also resulted in significant time- and concentration-dependent inhibition with both isolated enzymes and cell lysates. This inhibition was not metal ion, oxygen, superoxide dismutase, or catalase dependent, suggesting that inhibition is not radical mediated. These effects are suggested to be due to direct adduction of the free- or protein-bound carbonyls with the target enzyme. Such an interpretation is supported by the detection of the loss of thiol groups on GAPDH and the detection of cross-linked materials on protein gels. Though direct comparison of the extent of inhibition induced by free versus protein-bound carbonyls was not possible, the significantly higher concentrations of the latter materials over the former in diabetic plasma and cells lead us to suggest that alterations in the activity of key cellular enzymes induced by glycated proteins may play a significant role in the development of diabetic complications.

AB - Diabetic plasma contains elevated levels of glucose and various low-molecular-weight carbonyl compounds derived from the metabolism of glucose and related materials. These compounds react with protein side chains (Arg, Lys, Cys, and His) to give glycated materials and advanced glycation end products. In this study, we have examined the effect of glucose and carbonyl compounds (methylglyoxal, glyoxal, glycolaldehyde, and hydroxyacetone), and glycation products arising from reaction of these materials with model proteins, on the activity of three key cellular enzymes: glyceraldehyde-3-phosphate dehydrogenase (GAPDH), glutathione reductase, and lactate dehydrogenase, both in isolation and in cell lysates. In contrast to glucose (1M, both fresh and aged for 8 weeks), which had no effect, marked inhibition of all three enzymes was observed with methylglyoxal and glyoxal. GAPDH was also inhibited by glycolaldehyde and hydroxyacetone. Incubation of these enzymes with proteins that had been preglycated with methylglyoxal, but not glucose, also resulted in significant time- and concentration-dependent inhibition with both isolated enzymes and cell lysates. This inhibition was not metal ion, oxygen, superoxide dismutase, or catalase dependent, suggesting that inhibition is not radical mediated. These effects are suggested to be due to direct adduction of the free- or protein-bound carbonyls with the target enzyme. Such an interpretation is supported by the detection of the loss of thiol groups on GAPDH and the detection of cross-linked materials on protein gels. Though direct comparison of the extent of inhibition induced by free versus protein-bound carbonyls was not possible, the significantly higher concentrations of the latter materials over the former in diabetic plasma and cells lead us to suggest that alterations in the activity of key cellular enzymes induced by glycated proteins may play a significant role in the development of diabetic complications.

KW - Acetaldehyde

KW - Acetone

KW - Aldehydes

KW - Animals

KW - Cells, Cultured

KW - Enzyme Activation

KW - Enzymes

KW - Glucose

KW - Glutathione Reductase

KW - Glyceraldehyde 3-Phosphate Dehydrogenase (NADP+)

KW - Glycosylation End Products, Advanced

KW - Glyoxal

KW - L-Lactate Dehydrogenase

KW - Mice

KW - Molecular Weight

KW - Proteins

KW - Pyruvaldehyde

KW - Sulfhydryl Compounds

M3 - Journal article

VL - 403

SP - 259

EP - 269

JO - Archives of Biochemistry and Biophysics

JF - Archives of Biochemistry and Biophysics

SN - 0003-9861

IS - 2

ER -

ID: 138277031