Edible vegetables as a source of aldose reductase differential inhibitors.
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.
University of Pisa, Department of Biology, Pisa, Italy.
Francesco
F
Balestri
University of Pisa, Department of Biology, Pisa, Italy; Interdepartmental Research Center Nutrafood "Nutraceuticals and Food for Health", University of Pisa, Pisa, Italy.
Carlo
C
Sorce
University of Pisa, Department of Biology, Pisa, Italy; Interdepartmental Research Center Nutrafood "Nutraceuticals and Food for Health", University of Pisa, Pisa, Italy.
Roberta
R
Moschini
University of Pisa, Department of Biology, Pisa, Italy; Interdepartmental Research Center Nutrafood "Nutraceuticals and Food for Health", University of Pisa, Pisa, Italy.
Mario
M
Cappiello
University of Pisa, Department of Biology, Pisa, Italy; Tuscany Region PhD School in Biochemistry and Molecular Biology, Italy.
Livia
L
Misuri
University of Pisa, Department of Biology, Pisa, Italy; Interdepartmental Research Center Nutrafood "Nutraceuticals and Food for Health", University of Pisa, Pisa, Italy.
Antonella
A
Del Corso
University of Pisa, Department of Biology, Pisa, Italy; Interdepartmental Research Center Nutrafood "Nutraceuticals and Food for Health", University of Pisa, Pisa, Italy. Electronic address: umberto.mura@unipi.it.
Umberto
U
Mura
D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism; D006801:Humans; D027805:Phaseolus / Q000737:chemistry / Q000378:metabolism; D010936:Plant Extracts / Q000737:chemistry / Q000378:metabolism; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000737:chemistry / Q000302:isolation & purification; D013379:Substrate Specificity; D014675:Vegetables / Q000737:chemistry* / Q000378:metabolism
D004791:Enzyme Inhibitors; D010936:Plant Extracts; D011994:Recombinant Proteins; D000449:Aldehyde Reductase; D005947:Glucose
Aldo-keto reductases; Aldose reductase; Differential inhibitors; Functional foods; Phaseolus vulgaris