Methylglyoxal and the polyol pathway

  title={Methylglyoxal and the polyol pathway},
  author={R. I. Lindstad and J. McKinley-McKee},
  journal={FEBS Letters},
Methylglyoxal, 1,2‐propanediol and glycerol are shown to be substrates for sheep liver sorbitol dehydrogenase. With 1,2‐propanediol the enzymecatalyzed reaction occurs specifically with the R(−)‐enantiomer. The maximum velocities and the specificity constants obtained for the three‐carbon substrates are considerably lower than those reported previously for sorbitol, and suggest that rate‐determination is imposed by catalytic steps other than the enzyme‐coenzyme product dissociation. The present… Expand
Inhibition of sorbitol dehydrogenase by nucleosides and nucleotides.
The results indicate that the ribose moiety of the inhibitor structures is an important determinant for the observed effects, and the 2'-position of the Ribose ring exerts an effect with respect to inhibitor potency. Expand
The use of fluoro- and deoxy-substrate analogs to examine binding specificity and catalysis in the enzymes of the sorbitol pathway.
In contrast, both 6-fluoro- and 6-deoxy-D-glucitol are very good substrates for sorbitol dehydrogenase, indicating that the primary hydroxyl group at this position is not involved in substrate recognition by this enzyme. Expand
Inhibition and activation studies on sheep liver sorbitol dehydrogenase.
Kinetics with mainly sorbitol competitive inhibitors reveals that aliphatic thiols are generally the most potent inhibitors of enzyme activity, and NADH protects noncompetitively against inactivation. Expand
Stereo-selective affinity labelling of sheep liver sorbitol dehydrogenase by chloro-substituted analogues of 2-bromo-3-(5-imidazolyl)propionic acid.
The enantiomers of each label could form plausible complexes with the enzyme model, in agreement with the kinetic data, and the enantiomeric selectivity of the reaction appears due to the anion-binding site in sorbitol dehydrogenase being less developed than in horse liver alcohol dehydration. Expand
The non-oxidative degradation of ascorbic acid at physiological conditions.
ERU is an extremely reactive ketose, which rapidly glycates and crosslinks proteins, and therefore may mediate the AsA-dependent modification of protein (ascorbylation) seen in vitro, and also proposed to occur in vivo in human lens during diabetic and age-onset cataract formation. Expand
Reversible inhibition of sheep liver sorbitol dehydrogenase by thiol compounds.
Thionucleosides are established as a novel class of potent sorbitol dehydrogenase inhibitors and their inhibitory effect parallels that observed previously with the related enzyme horse liver alcohol dehydrogen enzyme and indicates that interaction with an enzymic hydrophobic site is important for inhibitor binding. Expand
Biosynthesis and Degradation
This chapter aims to discuss those biochemical interconversions involved in monosaccharide biosynthesis (anabolism) and degradation (catabolism). In particular, emphasis will center on defining theExpand
Protein Cross-linking by the Maillard Reaction
Results provide chemical evidence for protein cross-linking by dicarbonyl compounds in vivo and name this cross-link imidazolysine, detected in proteins by high performance liquid chromatography using a postcolumn derivatization method. Expand
Polyol pathway and diabetic peripheral neuropathy.
  • P. Oates
  • Medicine
  • International review of neurobiology
  • 2002
It is concluded that robust inhibition of metabolic flux through the polyol pathway in peripheral nerve will likely result in substantial clinical benefit in treating and preventing the currently intractable condition of diabetic peripheral neuropathy. Expand
The Polyol Pathway and Diabetic Retinopathy
In rats with experimental diabetes, drugs that inhibit AR are, as of today, the only drugs documented to prevent the whole spectrum of abnormalities induced by diabetes in glial cells, neurons, and vascular cells of the retina. Expand


The isolation of Sorbitol dehydrogenase from rat brain tissue is confirmation that all the constituents of the sorbitol (polyol) pathway are present in the brain and that fructose synthesis from glucose in this tissue proceeds via the intermediate formation of sor Bitol. Expand
Novel substrates and inhibitors of human liver sorbitol dehydrogenase.
  • W. Maret
  • Chemistry, Medicine
  • Advances in experimental medicine and biology
  • 1991
The formation of D-fructose from sorbitol was shown to be catalyzed by Sorbitol dehydrogenase (SDH)1 from rat liver homogenates, and several more recent findings prompted further investigation of structural features of this enzyme and the role of SDH in pathological conditions. Expand
Purification and characterization of human liver sorbitol dehydrogenase.
The present report describes the stereospecific oxidation of (2R,3R)-2,3-butanediol, indicating a more general function of sorbitol dehydrogenase in the metabolism of secondary alcohols. Expand
Molecular aspects of functional differences between alcohol and sorbitol dehydrogenases.
The amino acid sequence of sheep liver sorbitol dehydrogenase has been fitted to the high-resolution model of the homologous horse liver alcohol dehydrogenases by computer graphics, showing how altered enzymic activity might be brought about by structural changes of the kind that it is now possible to introduce by site-directed mutagenesis and recombinant DNA techniques. Expand
Metabolism of 2-oxoaldehydes in yeasts
The result indicated the possible role of glycolytic bypath as a detoxification system of methylglyoxal formed from l-threonine catabolism. Expand
Kinetic parameters for the elimination reaction catalyzed by triosephosphate isomerase and an estimation of the reaction's physiological significance.
Kinetic parameters for triosephosphate isomerase catalysis of the elimination reaction of an equilibrium mixture of dihydroxyacetone phosphate (DHAP) and D-glyceraldehyde-3-phosphate (DGAP) to formExpand
Enzyme relationships in a sorbitol pathway that bypasses glycolysis and pentose phosphates in glucose metabolism.
  • J. Jeffery, H. Jörnvall
  • Biology, Medicine
  • Proceedings of the National Academy of Sciences of the United States of America
  • 1983
The existence of parallel pathways and the occurrence of similar enzymic steps in one pathway may help to explain the abundance and multiplicity of enzymes such as reductases, aldolases, and alcohol dehydrogenases. Expand
The kinetic mechanism of sheep liver sorbitol dehydrogenase.
The relations between the kinetic parameters for both sorbitol oxidation and fructose reduction by sheep liver sorbitol dehydrogenase show that a Theorell-Chance compulsory order mechanism operatesExpand
Reduction of trioses by NADPH-dependent aldo-keto reductases. Aldose reductase, methylglyoxal, and diabetic complications.
A new integrative model of diabetic complications is proposed that combines the aldose reductase/polyol pathway theory and the nonenzymatic glycation theory except that emphasis is placed both on methylglyoxal/acetol metabolism and on glucose metabolism. Expand
Effect of Aldose Reductase Inhibitor (Sorbinil) on Integration of Polyol Pathway, Pentose Phosphate Pathway, and Glycolytic Route in Diabetic Rat Lens
The dual effects of diabetes in increasing 1) the lens content of glucose and glucose 6-phosphate and 2) the flux of glucose in the polyol pathway will result in an increased utilization of NADPH and production of NADH, factors favoring the flow of glucose through the PPP and restricting the glycolytic route in the diabetic rat lens are suggested. Expand