DESCRIPTION The inventors have found that the enzymes of the invention display protein and nucleic acid deglycase activities, which has never been disclosed. Indeed, although an alleged glyoxalase activity had been proposed for the DJ-1 protein and for bacterial Hsp31 (Lee et al. , Hum Mol Genet. , 21 (1 ): 3215-25, 2012, Subedi et al. , Mol. Microbiol. 81 , 926-936), it was never suggested nor demonstrated that neither the DJ-1 protein, nor its bacterial homologs Hsp31 , YhbO and YajL, actually harbor a deglycase activity.
The enzymes of the invention are early protein deglycases which can notably use substrates such as aminocarbinols formed by reaction of arginines and lysines residues with methylglyoxal and glyoxal , and hemithioacetals formed by reaction of cysteines residues with methylglyoxal or glyoxal (as demonstrated in the experimental part herein). Moreover, the inventors have found that the enzymes of the invention can also use as substrates the aminocarbinols formed by reaction of nucleotides aminogroups with glyoxals.
Interestingly, the enzymes of the invention catalyse deglycation at the second time- level, which means that they are about 40,000-fold faster than fructosamine-3- kinases (FN3K), and also impressively faster than FN3K-related proteins. The enzymes of the invention can act at the hemithioacetal step (for glycated cysteines), or the aminocarbinol step (for glycated lysines, arginines and nucleotides), and release the repaired amino acid, protein or nucleotide/nucleic acid and an acid-alcohol (lactate from methylglyoxal and glycolate from glyoxal).
The enzymes of the invention can thus act as instant deglycases, on the first glycation intermediates (hemithioacetals and aminocarbinols), and thus prevent formation of late intermediates, including AGEs. Indeed, there is a precursor-product relationship between early glycation products (including hemithioacetals and aminocarbinols which can be deglycated by deglycases of the invention) and late intermediates (i.e. late glycation products), including AGEs.
Moreover, the inventors have shown that the enzymes of the invention, by the way of their deglycase activity, can restore the activity of glycated proteins and enzymes such as bovine serum albumin, glyceraldehyde-3-phosphate dehydrogenase, fructose biphosphate aldolase and aspartate transaminase, i.e. proteins with cysteine or lysine and/or arginine residue in their active site. The enzymes of the invention can therefore be used to either to prevent or to reverse glycation on free lysine, arginine and lysine, and on lysyl-, arginyl- and cysteinyl residues of proteins, as well as on amino groups of free nucleic acids (particularly guanine residues, which are most prone to glycation (Voulgaridou et al. Mutation Res. 71 1 , 13-27), and polynucleotides which has never been shown for any enzyme.
http://www.sumobrain...15140348A2.html
Boosting your body's on glycation removal or deglycases seems like one of the best ways of stopping and reversing AGEs and the increase in bad NF-kB and short telomeres etc that come with it.
I hope the better qualified and experienced members here will read this patent and post their thoughts.
For us amature enthusiasts:
The invention thus further pertains to the use of DJ-1 inducers, preferably isothiocyanates, such as sulforaphane for example, or plant extracts, such as those from Butea frondosa or Butea monosperma for instance (Sujith et al. Asian J. of Pharmaceut. And Clin. Res. 4, 93).
The inventors have already shown that sulforaphane induces 3-fold the expression of Hsp31 and YhbO in bacterial cells (Figure 10B-C), and it is likely that it induces similarly DJ-1 in eukaryotic cells. Morover, it has been reported that sulforaphane induces Nrf2 (Kerns et al. PNAS 104, 14460, Xue et al. Diabetes, 57, 2809)) and also induces glyosalase
we tried to induce the deglycases with sulforaphane, a naturally occurring isothiocyanate derived from cruciferous vegetables, which is a potent inducer of phase 2 cytoprotective enzymes and protects cells against electrophiles, oxidative stress and inflammation (42) (sulforaphane likely acts by stabilization of Nrf2, which results in the induction of oxidative and electrophile stress resistance genes). As shown in Figure 10 B, C, sulforaphane, at micromolar concentrations which did not affect bacterial growth, induced Hsp31 and YhbO expression by 3 to 4-fold.
http://www.longecity...nable-efficacy/
https://cse.google.c....q=sulforaphane
ANTIDIABETIC ACTIVITY OF METHANOLIC EXTRACT OF BUTEA FRONDOSA LEAVES WITH ITS POSSIBLE MECHANISM OF ACTION
http://www.ajpcr.com...4Issue3/380.pdf
Examine.com
https://examine.com/...tea-monosperma/
Edited by Logic, 22 February 2016 - 05:27 PM.
