Effects of nonenzymatic glycosylation and fatty acids on tryptophan binding to human serum albumin

Bohney, J.P.; Feldhoff, Richard C.

doi:10.1016/0006-2952(92)90717-w

Cited by 32 publications

(21 citation statements)

References 28 publications

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“…An earlier study has shown that there was no significant difference in L-Trp binding between HSA and glycated HSA with 18 mg/ml of glucose [39], further supporting our results and suggestion that conformational and functional properties of HSA depend on the amount of glycation. Our results clearly showed that conformational change is a major factor for decreasing the affinity and that the amount and degree of glycation also influence the binding affinity to HSA.…”

Section: Discussionsupporting

confidence: 93%

Spectroscopic Studies of the Effects of Glycation of Human Serum Albumin on L-Trp Binding

Barzegar

Moosavi-Movahedi²,

Sattarahmady³

et al. 2007

PPL

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Modification of proteins by nonenzymatic glycation is one of the underlying factors that contribute to the development of the complications of diabetes. Human serum albumin (HSA) is one of the major targets of interaction with glucose through the Maillard reaction. The effects of 1 and 5 mg/ml glucose concentrations, which are consistent with blood glucose levels found in diabetic patients, on human serum albumin were studied by circular dichroism and fluorescence spectroscopy in sodium phosphate buffer, pH 7.4. Partial denaturation and changes in the structural integrity of HSA are caused by glycation at lower (1 mg/ml) and higher (5 mg/ml) concentrations of glucose. To study the relationship between structure and function, we investigated the interaction of L-tryptophan (L-Trp) with glycated and non-glycated HSA. The results showed that L-Trp, as the only free amino acid that substantially binds to HSA, has a lower affinity for the glycated form (especially at low concentrations of glucose) than for non-glycated HSA.

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Section: Discussionsupporting

confidence: 93%

Spectroscopic Studies of the Effects of Glycation of Human Serum Albumin on L-Trp Binding

Barzegar

Moosavi-Movahedi²,

Sattarahmady³

et al. 2007

PPL

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“…Albumin concentration did not change, so the binding mechanism of amino acid to albumin itself may also be modified, as observed in malnourished rats and human infants [29, 30]. Since albumin in the diabetic patient is also a glycated protein [31], its capacity for binding L -Trp may be decreased. This may also favor a further increase of L -Trp plasma concentration.…”

Section: Discussionmentioning

confidence: 99%

A Functional Disturbance in the Auditory Cortex Related to a Low Serotonergic Neurotransmission in Women with Type 2 Diabetes

Manjarrez-Gutiérrez¹,

Vázquez²,

Delgado

et al. 2007

Neuroendocrinology

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Background/Aims: To determine if the slope of the amplitude/stimulus intensity function (ASF) of the N1/P2 component of the auditory evoked potential was increased in women with type 2 diabetes reflecting a low brain serotonergic activity in the auditory cortex. Methods: In a comparative study in women with type 2 diabetes and controls, we measured free, bound and total plasma L-tryptophan (L-Trp), neutral amino acids (NAA) and free fatty acids (FFA) and recorded the N1/P2 component of the auditory evoked potential. Results: The diabetic patients were overweight and FFA and NAA in plasma were significantly elevated. The free, bound to albumin and total L-Trp were decreased. The values of free/total L-Trp and free/NAA ratios were significantly lower. The latencies of N1 and P2 at all intensities and the slope ASF of the N1/P2 component significantly increased. Conclusion: The decrease of the free fraction of L-Trp in plasma and the increase of the ASF slope of the N1/P2 component reflect a functional relationship between the brain serotonergic activity and the N1/P2 changes in the auditory cortex, suggesting a cortical impaired activity associated with anomalies of brain serotonergic neurotransmission in women with type 2 diabetes. We proposed the ASF slope together with measurement of the plasma FFT as noninvasive clinical indicators of serotonergic neurotransmission in the brain in these as well as in other types of patients.

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“…These changes in binding might occur due to a change in local charge or secondary structure as a result of glycation [39,40]. This may explain why several drugs used to probe binding at Sudlow site II (e.g., dansylproline, ibuprofen and flufenamic acid) and Sudlow site I (e.g., warfarin and phenylbutazone) have been observed to give different binding behavior for glycated HSA vs normal HSA [23,24]. These results suggest that further research is warranted in examining the effects of glycation on the binding of drugs to HSA and on the changes that may occur in drug behavior as a result of such modifications.…”

Section: Characterization Of Modification On Glycated Hasmentioning

confidence: 99%

“…These modifications are of interest since past studies have suggested that the glycation of HSA can lead to alterations in the binding of this protein to drugs such as phenytoin, salicylate, ibuprofen, phenylbutazone and warfarin [8,[21][22][23][24]. Furthermore, the effect of glycation appears to vary between different binding regions on HSA [23,24].…”

Section: Introductionmentioning

confidence: 99%

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Characterization of glycation adducts on human serum albumin by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry

Cerny

Clarke³

et al. 2007

Clinica Chimica Acta

107

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Background-Non-enzymatic glycation of human serum albumin (HSA) is associated with the long-term complications of diabetes. We examined the structure and location of modifications on minimally glycated HSA and considered their possible impact on the binding of drugs to this protein.Methods-Minimally glycated and normal HSA (used as a control) were digested with trypsin, Glu-C or Lys-C, followed by fractionation of the resulting peptides and their analysis by matrixassisted laser desorption/ionization mass spectrometry (MALDI-TOF MS) to determine the structures and locations of glycation adducts.Results-Several specific lysine and arginine residues were identified as modification sites in minimally glycated HSA. Residues K12, K51, K199, K205, K439 and K538 were found to be modified through the formation of fructosyl-lysine, while the modification of K159 and K286 involved the formation of pyrraline, N ε -carboxymethyl-lysine respectively. Lysine K378 was found to give N ε -carboxyethyl-lysine in some forms of glycated HSA but fructosyl-lysine in other forms. Residues R160 and R472 produced a modification based on N ε -(5-hydro-4-imidazolon-2-yl) ornithine. Lysine R222 was modified to produce argpyrimidine, N ε -[5-(2,3,4-trihydroxybutyl)-5-hydro-4-imidazolon-2-yl]ornithine or tetrahydropyrimidine.Conclusions-With the exception of K12, K199, K378, K439 and K525, all of the observed sites of modification for minimally glycated HSA were new to this current study. The fact that many of these glycation-related modifications are located at or near known drug binding sites on HSA explains why some differences have been previously noted in the binding of certain drugs to normal vs glycated HSA.

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Effects of nonenzymatic glycosylation and fatty acids on tryptophan binding to human serum albumin

Cited by 32 publications

References 28 publications

Spectroscopic Studies of the Effects of Glycation of Human Serum Albumin on L-Trp Binding

Spectroscopic Studies of the Effects of Glycation of Human Serum Albumin on L-Trp Binding

A Functional Disturbance in the Auditory Cortex Related to a Low Serotonergic Neurotransmission in Women with Type 2 Diabetes

Characterization of glycation adducts on human serum albumin by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry

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