Inhibition of a-glucosidase

Shobana, S., Sreerama, Y. N., and Malleshi, N. G. (2009). Composition and enzyme inhibitory properties of finger millet (Eleusine coracana L.) seed coat phenolics Mode of inhibition of a-glucosidase and pancreatic amylase. Food Chem. 115,1268-1273. 

Kerem Z, BiUds I, Flaishman MA, Sivan L (2006) Antioxidant activity and inhibition of a-glucosidase by trani-resveratrol, piceid, and a novel trans-stilbene from the roots of Israeli Rumex bucephalophorus L. J Agric Food Chem 54 1243-1247... 

Figure 9. Diagrammatic representation of the glucose lowering effect of flavonoids and phenolic acids through inhibition of a-glucosidase enzyme activity in brush borders of small mtestme.

More recently, it was shown that the biotransformation of oleanolic acid (30), with F. Uni afforded, in low amoxmts, two oxidative metabolites, 2a,3p-dihydroxy-olean-12-en-28-oic acid (50) and 2a,3p,lip-trihydroxy-olean-12-en-28-oic acid (51) [52]. The structures (Figure 28.12) were characterized on the basis of spectroscopic studies. Metabolites exhibited a potent inhibition of a-glucosidase from Saccharomyces sp. using p-nitrophenyl a-D-glucopyranoside as a substrate. 

The first member of this class, acarbose, was introduced in the early 1990s. a-Glucosidase inhibitors slow the intestinal process of carbohydrate digestion by competitive inhibition of the activity of a-glucosidase enzymes located in the brush border of the enterocytes... 

When a-glucosidase activity is inhibited, carbohydrate digestion is prolonged and takes place further along the intestinal tract. This in turn delays and spreads the period of glucose absorption, which reduces the extent of the postprandial rise in blood glucose concentrations. The effectiveness of a-glucosidase inhibitors is dq en-dent on the consumption of a meal rich in complex carbohydrate. 

Fig. 3.—pH-Dependenceofthe Inhibition of -o-Glucosidase A, from Aspergillus wentiiby )3-D-Glucosylpyridinium Ion, left ordinate) and the Protonated Form of D-Glucosyl-amine right, calc, with pK, 5.6) and Nojirimycin (—A-, right, calc, with pK,... 

Saul R, Molyneux RJ, Elbein AD. (1984) Studies on the mechanism of castano-spermine inhibition of a- and 13-glucosidase. Arch Biochem Biophys2M 668-675. 

Fleet GWJ, Nicholas SJ, Smith PW, Evans SV, Fellows LE, Nash RJ. (1985) Potent competitive inhibition of a-galactosidase and a-glucosidase activity by l,4-dideoxy-l,4-iminopentitols Synthesis of l,4-dideoxy-l,4-imino-D-lyxitol and of both enantiomers of l,4-dideoxy-l,4-iminoarabinitol. 

This succinyl group avoids the formation of the pyranosidic ring and acts as a spacer to conjugate the mole-cule to resins or biopolymers. The succinylated analog of sucrose 41 (R= HO2CCH2CH2CO-) is not sweet, and it is unable to inhibit invertase. It is however an inhibitor of a-glucosidase from baker s yeast. 

The reduced glycemic index has been attributed to PPT-mediated inhibition of a-amyl-ase, maltase, or a-glucosidase (sucrase)," " but the inhibition of these enzymes is not relevant when volunteers have been given glucose per These observations are... 

Gowri, P. M, Tiwaii, A. K, Ali, A. Z, Rao, J. M. Inhibition of alpha-glucosidase and amylase by bartogenic add isolated from Barringtonia racemosa Roxb. seeds. Phytothe-raphy Research. (2007). 

Colorimetric determination of the produced a-D-glucose. Acarbose is added to inhibit unspecific a-glucosidases present in leukocytes [33]. 

Inhibitors can block the pathway at specific steps, causing the accumulation of biosynthetic intermediates. Castanospermine inhibits the a-glucosidase that removes the first glucose deoxymannojirimycin inhibits the a-mannosidase I that removes mannose from the Man8 intermediate, and swainsonine blocks the a-mannosidase II that removes mannose from the Man5 intermediate. In the presence of swainsonine, hybrid N-linked carbohydrates are synthesized. 

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