-
Biomolecules Sep 2020Pompe disease, also known as glycogen storage disease type II, is caused by the lack or deficiency of a single enzyme, lysosomal acid alpha-glucosidase, leading to... (Review)
Review
Pompe disease, also known as glycogen storage disease type II, is caused by the lack or deficiency of a single enzyme, lysosomal acid alpha-glucosidase, leading to severe cardiac and skeletal muscle myopathy due to progressive accumulation of glycogen. The discovery that acid alpha-glucosidase resides in the lysosome gave rise to the concept of lysosomal storage diseases, and Pompe disease became the first among many monogenic diseases caused by loss of lysosomal enzyme activities. The only disease-specific treatment available for Pompe disease patients is enzyme replacement therapy (ERT) which aims to halt the natural course of the illness. Both the success and limitations of ERT provided novel insights in the pathophysiology of the disease and motivated the scientific community to develop the next generation of therapies that have already progressed to the clinic.
Topics: Autophagy; Enzyme Replacement Therapy; Genetic Therapy; Glycogen; Glycogen Storage Disease Type II; Humans; Lysosomal Storage Diseases; Lysosomes; Muscle, Skeletal; alpha-Glucosidases
PubMed: 32962155
DOI: 10.3390/biom10091339 -
Journal of Mother and Child Oct 2020Pompe disease is an autosomal recessive lysosomal glycogen storage disorder caused by the deficiency of acid alpha-glucosidase and subsequent progressive glycogen... (Review)
Review
Pompe disease is an autosomal recessive lysosomal glycogen storage disorder caused by the deficiency of acid alpha-glucosidase and subsequent progressive glycogen accumulation due to mutations in the GAA gene. Pompe disease manifests with a broad spectrum of disease severity, ranging from severe infantile-onset diseases such as hypotonia and hypertrophic cardiomyopathy to late-onset diseases such as myopathy and respiratory compromise. The diagnosis requires demonstration of deficiency of the lysosomal acid alpha-glucosidase enzyme, which can be assayed in dried blood spot or liquid blood samples, together with supportive biomarker tests, and confirmed with molecular genetic analysis. Targeted screening of at-risk populations and universal newborn screening can result in earlier diagnosis and enable earlier treatment initiation, which result in the potential improvement of clinical outcomes. Disease-modifying treatment with enzyme replacement therapy has partially altered the natural history of the disease, but more efficacious novel therapies are under evaluation including second-generation enzyme replacement therapies, molecular chaperones and gene therapy approaches. Long-term survivors with Pompe disease are now manifesting novel aspects of the disease including widespread vascular disease, smooth muscle and central nervous system involvement, and these emerging phenotypes will require additional specific therapeutic approaches.
Topics: Enzyme Replacement Therapy; Genetic Therapy; Glycogen Storage Disease Type II; Humans; alpha-Glucosidases
PubMed: 33554498
DOI: 10.34763/jmotherandchild.20202402si.2001.000002 -
Biomolecules Aug 2023Pompe disease (PD) is an autosomal recessive disorder caused by mutations in the gene that lead to a deficiency in the acid alpha-glucosidase enzyme. Two clinical... (Review)
Review
Pompe disease (PD) is an autosomal recessive disorder caused by mutations in the gene that lead to a deficiency in the acid alpha-glucosidase enzyme. Two clinical presentations are usually considered, named infantile-onset Pompe disease (IOPD) and late-onset Pompe disease (LOPD), which differ in age of onset, organ involvement, and severity of disease. Assessment of acid alpha-glucosidase activity on a dried blood spot is the first-line screening test, which needs to be confirmed by genetic analysis in case of suspected deficiency. LOPD is a multi-system disease, thus requiring a multidisciplinary approach for efficacious management. Enzyme replacement therapy (ERT), which was introduced over 15 years ago, changes the natural progression of the disease. However, it has limitations, including a reduction in efficacy over time and heterogeneous therapeutic responses among patients. Novel therapeutic approaches, such as gene therapy, are currently under study. We provide a comprehensive review of diagnostic advances in LOPD and a critical discussion about the advantages and limitations of current and future treatments.
Topics: Humans; Glycogen Storage Disease Type II; alpha-Glucosidases; Mutation; Genetic Therapy; Enzyme Replacement Therapy
PubMed: 37759679
DOI: 10.3390/biom13091279 -
Food and Chemical Toxicology : An... Nov 2020Recently the use of bioactive α-glucosidase inhibitors for the treatment of diabetes have been proven to be the most efficient remedy for controlling postprandial... (Review)
Review
Recently the use of bioactive α-glucosidase inhibitors for the treatment of diabetes have been proven to be the most efficient remedy for controlling postprandial hyperglycemia and its detrimental physiological complications, especially in type 2 diabetes. The carbohydrate hydrolysing enzyme, α-glucosidase, is generally competitively inhibited by the α-glucosidase inhibitors and results in the delayed glucose absorption in small intestine, ultimately controlling the postprandial hyperglycemia. Here we have reviewed the most recent updates in the bioactive α-glucosidase inhibitors category. This review provides an overview of the α-glucosidase inhibitory potentials and efficiency of controlling postprandial hyperglycemia of various bioactive compounds such as flavonoids, phenolic compound, polysaccharide, betulinic acid, tannins, anthocyanins, steroids, polyol, polyphenols, galangin, procyanidins, hydroxyl-α-sanshool, hydroxyl-β-sanshool, erythritol, ganomycin, caffeoylquinic acid, resin glycosides, saponins, avicularin, oleanolic acids, urasolic acid, ethanolic extracts etc., from various dietary and non-dietary naturally occurring sources.
Topics: Animals; Diabetes Mellitus, Type 2; Glycoside Hydrolase Inhibitors; Humans; Molecular Structure; Plant Extracts; alpha-Glucosidases
PubMed: 32916220
DOI: 10.1016/j.fct.2020.111738 -
Biomolecules Dec 2021Type-II diabetes mellitus (T2DM) results from a combination of genetic and lifestyle factors, and the prevalence of T2DM is increasing worldwide. Clinically, both... (Review)
Review
Type-II diabetes mellitus (T2DM) results from a combination of genetic and lifestyle factors, and the prevalence of T2DM is increasing worldwide. Clinically, both α-glucosidase and α-amylase enzymes inhibitors can suppress peaks of postprandial glucose with surplus adverse effects, leading to efforts devoted to urgently seeking new anti-diabetes drugs from natural sources for delayed starch digestion. This review attempts to explore 10 families e.g., , , , , , , , and as medicinal plants, and folk and herb medicines for lowering blood glucose level, or alternative anti-diabetic natural products. Many natural products have been studied in silico, in vitro, and in vivo assays to restrain hyperglycemia. In addition, natural products, and particularly polyphenols, possess diverse structures for exploring them as inhibitors of α-glucosidase and α-amylase. Interestingly, an in silico discovery approach using natural compounds via virtual screening could directly target α-glucosidase and α-amylase enzymes through molecular modeling. , , Studio, and have been used to discover new candidates as inhibitors or activators. While docking score, binding energy (Kcal/mol), the number of hydrogen bonds, or interactions with critical amino acid residues have been taken into concerning the reliability of software for validation of enzymatic analysis, in vitro cell assay and in vivo animal tests are required to obtain leads, hits, and candidates in drug discovery and development.
Topics: Computer Simulation; Diabetes Mellitus, Type 2; Drug Evaluation, Preclinical; Gene Expression Regulation, Enzymologic; Glycoside Hydrolase Inhibitors; Humans; Hydrogen Bonding; Hypoglycemic Agents; Molecular Docking Simulation; Plants, Medicinal; Polyphenols; alpha-Amylases; alpha-Glucosidases
PubMed: 34944521
DOI: 10.3390/biom11121877 -
Food Chemistry Nov 2021Inhibition of maltase, sucrase, isomaltase and glucoamylase activity by acarbose, epigallocatechin gallate, epicatechin gallate and four polyphenol-rich tea extract from...
Inhibition of maltase, sucrase, isomaltase and glucoamylase activity by acarbose, epigallocatechin gallate, epicatechin gallate and four polyphenol-rich tea extract from white, green, oolong, black tea, were investigated by using rat intestinal enzymes and human Caco-2 cells. Regarding rat intestinal enzyme mixture, all four tea extracts were very effective in inhibiting maltase and glucoamylase activity, but only white tea extract inhibited sucrase and isomaltase activity and the inhibition was limited. Mixed-type inhibition on rat maltase activity was observed. Tea extracts in combination with acarbose, produced a synergistic inhibitory effect on rat maltase activity. Caco-2 cells experiments were conducted in Transwells. Green tea extract and epigallocatechin gallate show dose-dependent inhibition on human sucrase activity, but no inhibition on rat sucrase activity. The opposite was observed on maltase activity. The results highlighted the different response in the two investigated model systems and show that tea polyphenols are good inhibitors for α-glucosidase activity.
Topics: Acarbose; Animals; Caco-2 Cells; Catechin; Glucan 1,4-alpha-Glucosidase; Glycoside Hydrolase Inhibitors; Glycoside Hydrolases; Humans; Intestines; Kinetics; Oligo-1,6-Glucosidase; Plant Extracts; Polyphenols; Rats; Sucrase; Tea; alpha-Glucosidases
PubMed: 34029903
DOI: 10.1016/j.foodchem.2021.130047 -
Cellular and Molecular Life Sciences :... Jul 2016α-Glucosidases (AGases) and α-1,4-glucan lyases (GLases) catalyze the degradation of α-glucosidic linkages at the non-reducing ends of substrates to release... (Review)
Review
α-Glucosidases (AGases) and α-1,4-glucan lyases (GLases) catalyze the degradation of α-glucosidic linkages at the non-reducing ends of substrates to release α-glucose and anhydrofructose, respectively. The AGases belong to glycoside hydrolase (GH) families 13 and 31, and the GLases belong to GH31 and share the same structural fold with GH31 AGases. GH13 and GH31 AGases show diverse functions upon the hydrolysis of substrates, having linkage specificities and size preferences, as well as upon transglucosylation, forming specific α-glucosidic linkages. The crystal structures of both enzymes were determined using free and ligand-bound forms, which enabled us to understand the important structural elements responsible for the diverse functions. A series of mutational approaches revealed features of the structural elements. In particular, amino-acid residues in plus subsites are of significance, because they regulate transglucosylation, which is used in the production of industrially valuable oligosaccharides. The recently solved three-dimensional structure of GLase from red seaweed revealed the amino-acid residues essential for lyase activity and the strict recognition of the α-(1 → 4)-glucosidic substrate linkage. The former was introduced to the GH31 AGase, and the resultant mutant displayed GLase activity. GH13 and GH31 AGases hydrate anhydrofructose to produce glucose, suggesting that AGases are involved in the catabolic pathway used to salvage unutilized anhydrofructose.
Topics: Amino Acid Sequence; Glycosylation; Models, Molecular; Polysaccharide-Lyases; Substrate Specificity; Sucrose; alpha-Glucosidases
PubMed: 27137181
DOI: 10.1007/s00018-016-2247-5 -
Molecules (Basel, Switzerland) May 2022Diabetes mellitus is a metabolic disorder and is a global challenge to the current medicinal chemists and pharmacologists. This research has been designed to isolate and...
Diabetes mellitus is a metabolic disorder and is a global challenge to the current medicinal chemists and pharmacologists. This research has been designed to isolate and evaluate antidiabetic bioactives from . The crude extracts, semi-purified and pure bioactives have been used in all in vitro assays. The in vitro α-glucosidase, α-amylase and DPPH free radical activities have been performed on all plant samples. The initial activities showed that ethyl acetate () was the potent fraction in all the assays. This fraction was initially semi-purified to obtain -. Among the semi-purified fractions, was dominant, exhibiting potent IC values in all the in vitro assays. Based on the potency and availability of materials, was subjected to further purification to obtain compounds (2,4-dichloro-6-hydroxy-3,5-dimethoxytoluene) and (2-methyl-6-(4-methylphenyl)-2-hepten-4-one). The two isolated compounds were characterized by mass and NMR analyses. The compounds and showed excellent inhibitions against α-glucosidase (21.45 for and 15.03 for μg/mL), α-amylase (17.65 and 16.56 μg/mL) and DPPH free radicals (7.62 and 14.30 μg/mL). Our study provides baseline research for the antidiabetic bioactives exploration from . The bioactive compounds can be evaluated in animals-based antidiabetic activity in future.
Topics: Animals; Antioxidants; Fragaria; Hypoglycemic Agents; Plant Extracts; alpha-Amylases; alpha-Glucosidases
PubMed: 35684382
DOI: 10.3390/molecules27113444 -
Nutrients Oct 2023With the change in people's lifestyle, diabetes has emerged as a chronic disease that poses a serious threat to human health, alongside tumor, cardiovascular, and... (Review)
Review
With the change in people's lifestyle, diabetes has emerged as a chronic disease that poses a serious threat to human health, alongside tumor, cardiovascular, and cerebrovascular diseases. α-glucosidase inhibitors, which are oral drugs, have proven effective in preventing and managing this disease. Studies have suggested that bioactive peptides could serve as a potential source of α-glucosidase inhibitors. These peptides possess certain hypoglycemic activity and can effectively regulate postprandial blood glucose levels by inhibiting α-glucosidase activity, thus intervening and regulating diabetes. This paper provides a systematic summary of the sources, isolation, purification, bioavailability, and possible mechanisms of α-glucosidase inhibitory peptides. The sources of the α-glucosidase inhibitory peptides were introduced with emphasis on animals, plants, and microorganisms. This paper also points out the problems in the research process of α-glucosidase inhibitory peptide, with a view to providing certain theoretical support for the further study of this peptide.
Topics: Animals; Humans; Glycoside Hydrolase Inhibitors; alpha-Glucosidases; Peptides; Hypoglycemic Agents; Diabetes Mellitus
PubMed: 37836551
DOI: 10.3390/nu15194267 -
Journal of Enzyme Inhibition and... Dec 2023Natural α-glucosidase inhibitors from plant-based foods such as catechins offer an attractive strategy for their potential anti-diabetic effects. In this study,...
Natural α-glucosidase inhibitors from plant-based foods such as catechins offer an attractive strategy for their potential anti-diabetic effects. In this study, infusions of three different tea types (green, white, and oolong) were investigated for their total phenolic (TPC) and catechins (EGCG, ECG, EGC, and EC) content, and for their α-glucosidase inhibitory activities. We observed that the level of TPC in white tea was significantly higher compared to oolong and green tea, which suggests higher content of EGCG and ECG catechins in fresh young leaves. Our findings showed that the higher content of such catechins in the infusion of white tea well correlated with a strong inhibition of α-glucosidase, and such inhibition was demonstrated to be more effective than the FDA-approved drug acarbose. Then, we computationally explored the molecular requirements for enzyme inhibition, especially for the most active catechins EGCG and ECG, as well as their disposition/stability within the active site.
Topics: alpha-Glucosidases; Catechin; Phenols; Plant Extracts; Tea; Glycoside Hydrolase Inhibitors
PubMed: 37470394
DOI: 10.1080/14756366.2023.2236802