Modulation of aldose reductase activity by aldose hemiacetals

Balestri, Francesco; Cappiello, Mario; Moschini, Roberta; Rotondo, Rossella; Abate, Marco; Corso, Antonella Del; Mura, Umberto

doi:10.1016/j.bbagen.2015.07.007

Cited by 18 publications

(22 citation statements)

References 52 publications

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“…These data suggest that a special recognition pattern must occur both for aldoses and for hydrophobic substrates; these patterns should be specific for each substrate typology and it may be possible to envisage specific inhibitors. Another particular aspect that distinguishes the targeting of the enzyme while catalyzing the aldose reduction with respect to the hydrophobic aldehyde reduction, is the non-hyperbolic inhibition exerted on the enzyme by haemiacetals [25]. In this regard it would be advisable to search for differential inhibitors in conditions in which both agonist substrates were present.…”

Section: -Ar As a Target Of Differential Inhibitionmentioning

confidence: 99%

Edible vegetables as a source of aldose reductase differential inhibitors

Balestri

Sorce

Moschini

et al. 2017

Chemico-Biological Interactions

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The hyperactivity of aldose reductase (AR) on glucose in diabetic conditions or on glutathionyl-hydroxynonenal in oxidative stress conditions, the source of cell damage and inflammation, appear to be balanced by the detoxifying action exerted by the enzyme. This detoxification acts on cytotoxic hydrophobic aldehydes deriving from membrane peroxidative processes. This may contribute to the failure in drug development for humans to favorably intervene in diabetic complications and inflammation, despite the specificity and high efficiency of several available aldose reductase inhibitors. This paper presents additional features to a previously proposed approach, on inhibiting the enzyme through molecules able to preferentially inhibit the enzyme depending on the substrate the enzyme is working on. These differential inhibitors (ARDIs) should act on glucose reduction catalyzed by AR without little or no effect on the reduction of alkenals or alkanals. The reasons why AR may be an eligible enzyme for differential inhibition are considered. These mainly refer to the evidence that, although AR is an unspecific enzyme that recognizes different substrates such as aldoses and hydrophobic aldehydes, it nevertheless displays a certain degree of specificity among substrates of the same class. After screening on edible vegetables, indications of the presence of molecules potentially acting as ARDIs are reported.

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Section: -Ar As a Target Of Differential Inhibitionmentioning

confidence: 99%

Edible vegetables as a source of aldose reductase differential inhibitors

Balestri

Sorce

Moschini

et al. 2017

Chemico-Biological Interactions

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“…Another example of an extreme case of a molecule, used in its truly least stable and least available form, is the rather improbable, but real, use of glucose through its free aldehyde form by aldose reductase (Balestri et al 2015) in the polyol pathway. In this case, however, we cannot disregard the complex inhibitory action on the reaction exerted by glucose hemiacetal (Del Corso et al 2008) and the fact that the glucose flux through the polyol pathway, which is significant and damaging in the hyperglycemic conditions associated with diabetes, is almost negligible in physiological normoglycemic conditions (Brownlee 2005).…”

Section: Recruitment Of Molecules To Assemble Metabolic Pathwaysmentioning

confidence: 99%

How the chemical features of molecules may have addressed the settlement of metabolic steps

et al. 2017

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Introduction While the evolutionary adaptation of enzymes to their own substrates is a well assessed and rationalized field, how molecules have been originally selected in order to initiate and assemble convenient metabolic pathways is a fascinating, but still debated argument. Objectives Aim of the present study is to give a rationale for the preferential selection of specific molecules to generate metabolic pathways. Methods he comparison of structural features of molecules, through an inductive methodological approach, offer a reading key to cautiously propose a determining factor for their metabolic recruitment. Results Starting with some commonplaces occurring in the structural representation of relevant carbohydrates, such as glucose, fructose and ribose, arguments are presented in associating stable structural determinants of these molecules and their peculiar occurrence in metabolic pathways. Conclusions Among other possible factors, the reliability of the structural asset of a molecule may be relevant or its selection among structurally and, a priori, functionally similar molecules.

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“…In addition to body weight loss, vascular devastation and nephropathy, eye diseases such as cataract and retinopathy might be induced by DM (Srivastava et al, 2011;Akash et al, 2015). In addition, overproduction of reactive oxygen species (ROS) through up-regulation of aldose reductase and down-regulation of antioxidant systems has been reported in DM (Srivastava et al, 2011;Nazıroğlu et al, 2012;Balestri et al, 2015). Non-enzymatic and autooxidative glycosylation metabolic stress through activation of energy metabolism and activity of the sorbitol path in DM are activated by overproduction of ROS (Singh and Jialal, 2008).…”

Section: List Of Abbreviations;mentioning

confidence: 99%

Melatonin reduces lens oxidative stress level in STZ-induced diabetic rats through supporting glutathione peroxidase and reduced glutathione values

Kahya¹,

Nazıroğlu²

2016

Journal of Cellular Neuroscience and Oxidative Stress

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Journal of Cellular Neuroscience and Oxidative Stress is an online journal that publishes original research articles, reviews and short reviews on the molecular basis of biophysical, physiological and pharmacological processes that regulate cellular function, and the control or alteration of these processes by the action of receptors, neurotransmitters, second messengers, cation, anions, drugs or disease. Areas of particular interest are four topics. They are; A-Ion Channels (Na +-K + Channels, Clchannels, Ca 2+ channels, ADP-Ribose and metabolism of NAD + , Patch-Clamp applications) B-Oxidative Stress (Antioxidant vitamins, antioxidant enzymes, metabolism of nitric oxide, oxidative stress, biophysics, biochemistry and physiology of free oxygen radicals) C-Interaction Between Oxidative Stress and Ion Channels in Neuroscience (Effects of the oxidative stress on the activation of the voltage sensitive cation channels, effect of ADP-Ribose and NAD + on activation of the cation channels which are sensitive to voltage, effect of the oxidative stress on activation of the TRP channels in neurodegenerative diseases such Parkinson's and Alzheimer's diseases) D-Gene and Oxidative Stress (Gene abnormalities. Interaction between gene and free radicals. Gene anomalies and iron. Role of radiation and cancer on gene polymorphism)

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Modulation of aldose reductase activity by aldose hemiacetals

Abstract: The discovery of aldose reductase modulation by hemiacetals offers a new perspective in searching for aldose reductase inhibitors to be developed as drugs counteracting the onset of diabetic complications.

Cited by 18 publications

References 52 publications

Edible vegetables as a source of aldose reductase differential inhibitors

Edible vegetables as a source of aldose reductase differential inhibitors

How the chemical features of molecules may have addressed the settlement of metabolic steps

Melatonin reduces lens oxidative stress level in STZ-induced diabetic rats through supporting glutathione peroxidase and reduced glutathione values

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