Impact of Reactive Dicarbonyls on Biological Macromolecules- Role in Metabolic Disorders

Ahmad, Saheem; Rehman, Shahnawaz

doi:10.2174/138920372109201105114029

Cited by 3 publications

(5 citation statements)

References 11 publications

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“…The intermediate Amadori products may further undergo rearrangements, dehydrations, and cyclizations to form highly stable advanced glycation end products (AGEs) 12–15 . The formation of heterogeneous AGEs is slow and continuous, but the hyperglycemic condition can cause a multi‐fold increase in AGEs such as carboxyethyllysine (CEL), pentosidine, and carboxymethyllysine (CML) 16–18 …”

Section: Introductionmentioning

confidence: 99%

“…[12][13][14][15] The formation of heterogeneous AGEs is slow and continuous, but the hyperglycemic condition can cause a multi-fold increase in AGEs such as carboxyethyllysine (CEL), pentosidine, and carboxymethyllysine (CML). [16][17][18] D-ribose is a naturally occurring, aldofuranose portraying five-membered ring sugar and is known to be vulnerable to reacting with an amino group of proteins present in all living cells and is also associated with cellular metabolism. Structurally, Dribose has a hydroxyl group in its second carbon position, which makes it more reactive than other sugars, including deoxyribose, which has one hydrogen atom in its second carbon position.…”

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confidence: 99%

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Nonenzymatic glycosylation of isolated human immunoglobulin‐G by D‐ribose

Ahmad

Alshaghdali

Rehman

et al. 2022

Cell Biochemistry & Function

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Glycation is vital in terms of its damaging effect on macromolecules resulting in the formation of end products, which are highly reactive and cross‐linked irreversible structures, known as advanced glycation end products (AGEs). The continuous accumulation of AGEs is associated with severe diabetes and its associated ailments. Saccharides with their reducing ends can glycate amino acid side chains of proteins, among them glucose is well‐known for its potent glycating capability. However, other reducing sugars can be more reactive glycating agents than glucose. The D‐ribose is a pentose sugar‐containing an active aldehyde group in its open form and is responsible for affecting the biological processes of the cellular system. D‐ribose, a key component of many biological molecules, is more reactive than most reducing sugars. Protein glycation by reducing monosaccharides such as D‐ribose promotes the accelerated formation of AGEs that could lead to cellular impairments and dysfunctions. Also, under a physiological cellular state, the bioavailability rate of D‐ribose is much higher than that of glucose in diabetes, which makes this species much more active in protein glycation as compared with D‐glucose. Due to the abnormal level of D‐ribose in the biological system, the glycation of proteins with D‐ribose needs to be analyzed and addressed carefully. In the present study, human immunoglobulin G (IgG) was isolated and purified via affinity column chromatography. D‐ribose at 10 and 100 mM concentrations was used as glycating agent, for 1–12 days of incubation at 37°C. The postglycation changes in IgG molecule were characterized by UV‐visible and fluorescence spectroscopy, nitroblue tetrazolium assay, and various other physicochemical analyses for the confirmation of D‐ribose mediated IgG glycation.

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Section: Introductionmentioning

confidence: 99%

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confidence: 99%

Nonenzymatic glycosylation of isolated human immunoglobulin‐G by D‐ribose

Ahmad

Alshaghdali

Rehman

et al. 2022

Cell Biochemistry & Function

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“…When AGEs get deposited on plasma lipoproteins and in tissues, they bind to their specific receptors, RAGEs. Patients with diabetes are more likely to develop diabetes complications, osteoarthritis and age‐related cardiovascular disease because AGEs bind to RAGE at an accelerated pace 8–10 . A well‐known fact is that methylglyoxal (MTG) generates AGEs by reacting with biomacromolecules such as RNA, DNA, proteins, and lipoproteins.…”

Section: Introductionmentioning

confidence: 99%

“…Patients with diabetes are more likely to develop diabetes complications, osteoarthritis and agerelated cardiovascular disease because AGEs bind to RAGE at an accelerated pace. [8][9][10] A well-known fact is that methylglyoxal (MTG) generates AGEs by reacting with biomacromolecules such as RNA, DNA, proteins, and lipoproteins. AGE precursors including N-ecarboxymethyllysine (CML) and MTG, which are produced from food, have been demonstrated in human studies to increase inflammatory responses and oxidative stress in people with chronic conditions like diabetes.…”

Section: Introductionmentioning

confidence: 99%

Metformin encapsulated gold nanoparticles (MTF‐GNPs): A promising antiglycation agent

Alenazi

Saleem

Khaja

et al. 2022

Cell Biochemistry & Function

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The generation of advanced glycation end products (AGEs) through nonenzymatic protein glycation contributes to the pathogenesis of long‐lived diabetic problems. Metformin (MTF) is the very first drug having antihyperglycemic effects on type II diabetes mellitus which also possess interaction with dicarbonyl compounds and blocks the formation of AGEs. In the current study, MTF is bioconjugated with glycation‐derived synthesized gold nanoparticles (GNPs) of significant size. Additionally, using various biophysical and biochemical approaches, we investigated the antiglycating capacity MTF‐GNPs in contrast to MTF against d‐ribose‐derived glycation of bovine serum albumin. Our key findings via utilizing various assays demonstrated that MTF‐GNPs were able to inhibit AGEs development by reducing hyperchromicity, early glycation products, carbonyl content, hydxoxymethylfurfural content, production of fluorescent AGEs, normalizing the loss of secondary structure (i.e., α‐helix and β‐sheets) of proteins, elevating the levels of free lysine and free arginine more efficiently compared to pure MTF. Based on these results, we concluded that MTF‐GNPs possess a considerable antiglycation property and may be developed as an outstanding anti‐AGEs treatment drug. Further in vivo and clinical research are necessary to determine the therapeutic effects of MTF‐GNPs against AGE‐related and metabolic disorders.

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“…The glycation reaction proceeds with the formation of reversible Schiff's bases, to stable ketoamines or Amadori products, which finally lead to the formation of advanced glycation end products (AGEs) [ 4 , 5 ]. Moreover, autoxidation of glucose and glycoxidation of proteins give rise to reactive oxygen species (ROS) that lead to the generation of reactive carbonyl species (RCS) or dicarbonyls such as glyoxal (GO), methylglyoxal (MGO), and 3-deoxyglucosone (3-DG) [ 6 , 21 ]. Furthermore, shunting of excess glucose in the polyol pathway and glycolysis too results in the generation of RCS [ 7 – 9 ].…”

Section: Introductionmentioning

confidence: 99%

Gold Nanoparticle-Bioconjugated Aminoguanidine Inhibits Glycation Reaction: An In Vivo Study in a Diabetic Animal Model

Ahmad

Khan

Alouffi

et al. 2021

BioMed Research International

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Proteins undergo glycation resulting in the generation of advanced glycation end products (AGEs) that play a central role in the onset and advancement of diabetes-associated secondary complications. Aminoguanidine (AG) acts as an antiglycating agent by inhibiting AGE generation by blocking reactive carbonyl species (RCS) like, methylglyoxal (MGO). Previous studies on antiglycating behavior of AG gave promising results in the treatment of diabetes-associated microvascular complications, but it was discontinued as it was found to be toxic at high concentrations (>10 mmol/L). The current article aims at glycation inhibition by conjugating gold nanoparticles (Gnp) with less concentration of AG (0.5-1.0 mmol/L). The HPLC results showed that AG-Gnp fairly hampers the formation of glycation adducts. Moreover, the in vivo studies revealed AG-Gnp mediated inhibition in the production of total-AGEs and - N ε -(carboxymethyl)lysine (CML) in the diabetic rat model. This inhibition was found to be directly correlated with the antioxidant parameters, blood glucose, insulin, and glycosylated hemoglobin levels. Furthermore, the histopathology of AG-Gnp-treated rats showed good recovery in the damaged pancreatic tissue as compared to diabetic rats. We propose that this approach might increase the efficacy of AG at relatively low concentrations to avoid toxicity and might facilitate to overcome the hazardous actions of antiglycating drugs.

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Impact of Reactive Dicarbonyls on Biological Macromolecules- Role in Metabolic Disorders

Cited by 3 publications

References 11 publications

Nonenzymatic glycosylation of isolated human immunoglobulin‐G by D‐ribose

Nonenzymatic glycosylation of isolated human immunoglobulin‐G by D‐ribose

Metformin encapsulated gold nanoparticles (MTF‐GNPs): A promising antiglycation agent

Gold Nanoparticle-Bioconjugated Aminoguanidine Inhibits Glycation Reaction: An In Vivo Study in a Diabetic Animal Model

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