Inhibitory effects of pyridoxal phosphate, ascorbate and aminoguanidine on nonenzymatic glycosylation

Khatami, Mahin; Suldan, Zalman; David, Indira; Li, Weiye; Rockey, John H.

doi:10.1016/0024-3205(88)90484-5

Cited by 68 publications

(30 citation statements)

References 15 publications

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“…AA has also previously been shown to reduce nonenzymatic glycation of bovine serum albumin [23] and collagen [24] in vitro and of albumin and haemoglobin in human non-diabetic subjects in vivo [25]. Although we observed no effect of AA treatment on glycated haemoglobin levels of non-diabetic or STZdiabetic rats, we suggest that further studies on the effect of AA treatment on non-enzymatic glycation of intra-cellular proteins within tissues which develop diabetic complications are necessary.…”

Section: Discussioncontrasting

confidence: 48%

Tissue ascorbic acid and polyol pathway metabolism in experimental diabetes

et al. 1998

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Abnormalities of collagen synthesis [1] and increased oxidative stress [2] have been implicated in the pathogenesis of diabetic microangiopathy. Since ascorbic acid (AA; vitamin C) is an essential cofactor for prolyl hydroxylase, a key enzyme in the biosynthesis of collagen and is also an important antioxidant [3], AA metabolism may link these processes.Decreased plasma AA concentrations and increased turnover of AA to the oxidised metabolite dehydroascorbic acid (DHAA) have been reported in diabetic subjects [4±10], particularly in patients with poor glycaemic control [11] and/or microangiopathy [12,13]. Although (i) leucocyte AA concentration is reduced following intravenous glucose [14], (ii) in vitro cell culture studies [15±18] demonstrate competitive cellular uptake of glucose and AA and (iii) in Diabetologia (1998) Summary Previous studies demonstrating reduced plasma concentrations of ascorbic acid (AA) in diabetes and interactions between this vitamin and biochemical mechanisms such as synthesis of structural proteins, oxidative stress, polyol pathway and nonenzymatic glycation of proteins suggest that disturbed AA metabolism may be important in the pathogenesis of diabetic microangiopathy. However, limited information is available on the concentration of AA in tissues which develop diabetic complications. This study demonstrates reduced renal but not sciatic nerve or plasma AA concentration in two animal models of insulin-dependent diabetes mellitus, namely the STZ-diabetic rat and the spontaneously diabetic BB rat. Decreased lens AA concentration was also observed in STZ-diabetic rats. Improvement of glycaemic control by insulin treatment (albeit insufficient to achieve normoglycaemia) partially corrected lens and renal AA concentration in STZ-diabetic rats. AA treatment increased kidney and lens AA concentrations of STZ-diabetic and non-diabetic rats and corrected the abnormalities observed for untreated diabetic rats. Sciatic nerve AA concentration was not increased by AA treatment in any group. Tissue ratios of dehydroascorbic acid (DHAA)/AA, one index of oxidative stress, were not different between the diabetic and non-diabetic groups and were unaltered by AA supplementation. AA treatment of STZ-diabetic rats had no effect on elevated tissue concentrations of glucose, sorbitol and fructose or reduced myo-inositol concentration. The effect of reduced tissue AA levels in diabetes on either collagen synthesis or ability to combat increased free radical production is not known. However, correction of abnormal kidney and lens AA concentrations in experimental diabetes by AA supplementation suggests that if AA does have a role in the development or progression of the renal and ocular complications of diabetes, this treatment could be beneficial. [Diabetologia (1998) 41: 516±523]

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Section: Discussioncontrasting

confidence: 48%

Tissue ascorbic acid and polyol pathway metabolism in experimental diabetes

et al. 1998

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“…Little is known about the former possibility for these compounds. However, pyridoxal and pyridoxal phosphate, as aldehydes, are known to compete with sugars for Schiff base formation with protein amino groups and have, indeed, been proposed as inhibitors of glycation through this "competitive" mechanism (32,69,70). In the particular case of RNase, pyridoxal phosphate has been shown to act as an affinity label for the active site by interacting with critical Lys-41 and Lys-7 (59).…”

Section: Discussionmentioning

confidence: 99%

“…This is typified by the prominent AGE inhibitor aminoguanidine, or guanylhydrazine (Scheme 2), that can potentially react as a hydrazine with carbonyls of Amadori intermediates or can scavenge reactive dicarbonyls through its guanidinium moiety. Additionally, as a hydrazine it can block the reactive open chain carbonyl form of reducing sugars (32,33). Few studies have quantitatively measured the complete kinetics of protein glycation due to the slowness of the reactions with glucose, making it even more difficult to draw conclusions about inhibition.…”

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confidence: 99%

In Vitro Kinetic Studies of Formation of Antigenic Advanced Glycation End Products (AGEs)

Booth

Khalifah

Todd

et al. 1997

Journal of Biological Chemistry

263

194

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“…The protection against erythrose toxicity by aminoguanidine shown in Fig. 6 could have been because of prevention of the enolization and subsequent oxidation of the erythrose, because of formation of the hydrazide derivative (22,23), or to conversion of the ␣,␤-dicarbonyl oxidation product of erythrose to the asymmetrical triazine (24 -26) or to both actions. The profound toxicity of methylglyoxal and the complete protection against that toxicity provided by aminoguanidine indicate that much of the effect of the short chain sugars was because of ␣,␤-dicarbonyl oxidation products and that much of the protective effect of aminoguanidine was because of the trapping of these dicarbonyls, probably by conversion to triazines.…”

Section: Discussionmentioning

confidence: 99%

Superoxide Dependence of the Toxicity of Short Chain Sugars

Benov

Fridovich

1998

Journal of Biological Chemistry

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Erythrose inhibited the growth of a sodA sodB strain of Escherichia coli under aerobiosis; but did not inhibit anaerobic growth of the sodA sodB strain, or the aerobic growth of the superoxide dismutase (SOD)-competent parental strain. A SOD mimic protected the sodA sodB strain against the toxicity of erythrose as did the carbonyl-blocking reagents hydrazine and aminoguanidine. Three carbon sugars, such as glyceraldehyde and dihydroxy acetone, and the two carbon sugar glycolaldehyde, were similarly toxic in an O 2 . -dependent man-ner. An unidentified dialyzable component in E. coli extract augmented the oxidation of short chain sugars, and this was partially inhibitable by SOD. The toxicity of the short chain sugars appears to be because of an O 2 . -dependent oxidation to ␣,␤-dicarbonyl compounds.In keeping with this view was the O 2 . -independent toxicity of methylglyoxal.We have previously noted that ␣-hydroxycarbonyl compounds can autoxidize with the production of O 2 .(1). Cyanide, and to a lesser extent other nucleophiles, strongly accelerated this autoxidation, and the augmenting effect of preincubation at elevated pH indicated the involvement of an enediolate intermediate. This cyanide-catalyzed oxidation had been seen earlier with methylglyoxal (2, 3). Oxidation of ␣-hydroxycarbonyl compounds was subsequently seen to proceed as a chain reaction in which O 2 . could serve as both an initator and a propagator (4). The autoxidation of such compounds have been studied by others, who also noted O 2 . production (5, 6) and the role of enolization (5). ␣-Amino carbonyl compounds appear to behave in a similar way (7-9). The mutagenicity of ␣-hydroxycarbonyl compounds in Salmonella typhimurium was attributed to their ease of autoxidation with attendant oxy radical production (10). During an attempt to use erythrose as a carbon source for the growth of a sodA sodB strain of Escherichia coli, we noted an oxygen-dependent toxicity and set out to explore its mechanism. The data reported herein indicate a role for O 2 . in the toxicities of erythrose and shorter chain sugars. These results are relevant to the much slower process of nonenzymic glycation seen with long chain sugars, such as glucose, which exist primarily as internal hemiacetals and are therefore less reactive (11-15). MATERIALS AND METHODSD(Ϫ)-Erythrose was from Fluka, whereas aminoguanidine and methylglyoxal were obtained from Aldrich. DL-Glyceraldehyde, glycolaldehyde, dihydroxy acetone, and the phosphate esters of glyceraldehyde, erythrose, and dihydroxy acetone, were from Sigma. The strains of E. coli used in these studies were AB1157, which was the parental strain for JI132 that was sodA sodB (16). Starter cultures were usually grown overnight in aerobic LB medium at 37°C and were then diluted 200-fold into M9CA medium. LB and M9CA were as described (17). Anaerobiosis, when desired, was achieved in Gas Pack jars. These jars were opened at intervals to allow turbidimetry, following which the jars were evacuated and refilled with N 2 . Culture gro...

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Inhibitory effects of pyridoxal phosphate, ascorbate and aminoguanidine on nonenzymatic glycosylation

Cited by 68 publications

References 15 publications

Tissue ascorbic acid and polyol pathway metabolism in experimental diabetes

Tissue ascorbic acid and polyol pathway metabolism in experimental diabetes

In Vitro Kinetic Studies of Formation of Antigenic Advanced Glycation End Products (AGEs)

Superoxide Dependence of the Toxicity of Short Chain Sugars

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