α-Glucosidase (, (systematic name α-D-glucoside glucohydrolase) is a

glucosidase Glucosidases are the glycoside hydrolase enzymes categorized under the EC number 3.2.1. Function Alpha-glucosidases are enzymes involved in breaking down complex carbohydrates such as starch and glycogen into their monomers. They catalyze the ...

located in the

brush border A brush border (striated border or brush border membrane) is the microvillus-covered surface of simple cuboidal and simple columnar epithelium found in different parts of the body. Microvilli are approximately 100 nanometers in diameter and th ...

of the small intestine that acts upon α(1→4) bonds: : Hydrolysis of terminal, non-reducing (1→4)-linked α-D-glucose residues with release of D-glucose This is in contrast to β-glucosidase.

Terminology

GO:0090599, the broad sense

The

Gene Ontology The Gene Ontology (GO) is a major bioinformatics initiative to unify the representation of gene and gene product attributes across all species. More specifically, the project aims to: 1) maintain and develop its controlled vocabulary of gene and ...

entry GO:0090599 represents the broad sense of "alpha-glucosidase". It is defined as "catalysis of the hydrolysis of terminal, non-reducing alpha-linked alpha-D-glucose residue with release of alpha-D-glucose." In this sense, "alpha-glucosidase" can encompass a wide range of enzyme activitiess, differing by the linkage of their terminal (1→3, 1→4, or 1→6), the specific identity of their substrate (sucrose, maltose, or starch), among other aspects. See: Definition, GO Tree View.

EC 3.2.1.20, the narrow sense

The definition associated with

Enzyme Commission number The Enzyme Commission number (EC number) is a numerical classification scheme for enzymes, based on the chemical reactions they catalyze. As a system of enzyme nomenclature, every EC number is associated with a recommended name for the correspon ...

3.2.1.20 is narrower. It requires the linkage to be 1→4, and the preferred substrate to be smaller

oligosaccharides An oligosaccharide (; ) is a saccharide polymer containing a small number (typically three to ten) of monosaccharides (simple sugars). Oligosaccharides can have many functions including cell recognition and cell adhesion. They are normally presen ...

(as opposed to larger polysaccharides like

starch Starch or amylum is a polymeric carbohydrate consisting of numerous glucose units joined by glycosidic bonds. This polysaccharide is produced by most green plants for energy storage. Worldwide, it is the most common carbohydrate in human diet ...

: alpha-amylase would otherwise be included). Human genes that produce enzymes with activities specified by this EC number include: * MGAM is the "maltase-glucoamylase", found on the intestine brush border. *

GAA Gaa may refer to: * Gaa language, a language of Nigeria * gaa, the ISO 639 code for the Ga language of Ghana GAA may stand for: Compounds * Glacial (water-free), acetic acid * Acid alpha-glucosidase, also known as glucosidase, alpha; acid, an e ...

is the "acid alpha-glucosidase", found in the

lysosome A lysosome () is a membrane-bound organelle that is found in all mammalian cells, with the exception of red blood cells (erythrocytes). There are normally hundreds of lysosomes in the cytosol, where they function as the cell’s degradation cent ...

. * GANC, "neutral alpha-glucosidase C". Synonyms mentioned by the Commission include ''maltase, glucoinvertase, glucosidosucrase, maltase-glucoamylase, α-glucopyranosidase, glucosidoinvertase, α-D-glucosidase, α-glucoside hydrolase, α-1,4-glucosidase, α-D-glucoside glucohydrolase''. These names are not recommended because they may only refer to a specific activity of the enzyme, or a specific protein having this acvitity.

Mechanism

α-Glucosidase hydrolyzes terminal non-reducing (1→4)-linked α-glucose residues to release a single α-glucose molecule. α-Glucosidase is a carbohydrate-hydrolase that releases α-glucose as opposed to β-glucose. β-Glucose residues can be released by glucoamylase, a functionally similar enzyme. The substrate selectivity of α-glucosidase is due to subsite affinities of the enzyme's active site. Two proposed mechanisms include a nucleophilic displacement and an oxocarbenium ion intermediate. Catalytic reaction for maltase

* ''

Rhodnius prolixus ''Rhodnius prolixus'' is the principal triatomine vector of the Chagas parasite due to both its sylvatic and domestic populations in northern South America as well as to its exclusively domestic populations in Central America. It has a wide ran ...

'', a blood-sucking insect, forms hemozoin (Hz) during digestion of host hemoglobin. Hemozoin synthesis is dependent on the substrate binding site of α-glucosidase. * Trout liver α-glucosidases were extracted and characterized. It was shown that for one of the trout liver α-glucosidases maximum activity of the enzyme was increased by 80% during exercise in comparison to a resting trout. This change was shown to correlate to an activity increase for liver glycogen phosphorylase. It is proposed that α-glucosidase in the glucosidic path plays an important part in complementing the phosphorolytic pathway in the liver's metabolic response to energy demands of exercise. * Yeast and rat small intestinal α-glucosidases have been shown to be inhibited by several groups of flavonoids.

Structure

α-Glucosidases can be divided, according to primary structure, into two families. The gene coding for human lysosomal α-glucosidase is about 20 kb long and its structure has been cloned and confirmed. * Human lysosomal α-glucosidase has been studied for the significance of the Asp-518 and other residues in proximity of the enzyme's active site. It was found that substituting Asp-513 with Glu-513 interferes with posttranslational modification and intracellular transport of α-glucosidase's precursor. Additionally, the Trp-516 and Asp-518 residues have been deemed critical for the enzyme's catalytic functionality. * Kinetic changes in α-glucosidase have been shown to be induced by denaturants such as guanidinium chloride (GdmCl) and SDS solutions. These denaturants cause loss of activity and conformational change. A loss of enzyme activity occurs at much lower concentrations of denaturant than required for conformational changes. This leads to a conclusion that the enzyme's active site conformation is less stable than the whole enzyme conformation in response to the two denaturants.

Disease relevance

Glycogen storage disease type II Glycogen storage disease type II (GSD-II), also called Pompe disease, and formerly known as GSD-IIa or Limb–girdle muscular dystrophy 2V, is an autosomal recessive metabolic disorder which damages muscle and nerve cells throughout the body. ...

, also called Pompe disease: a disorder in which α-glucosidase is deficient. In 2006, the drug alglucosidase alfa became the first released treatment for Pompe disease and acts as an analog to α-glucosidase. Further studies of alglucosidase alfa revealed that

iminosugar An iminosugar, also known as an iminosaccharide, is any analog of a sugar where a nitrogen atom has replaced the oxygen atom in the ring of the structure. Iminosugars are common components of plants and may be responsible for some of their medic ...

s exhibit inhibition of the enzyme. It was found that one compound molecule binds to a single enzyme molecule. It was shown that 1-deoxynojirimycin (DNJ) would bind the strongest of the sugars tested and blocked the active site of the enzyme almost entirely. The studies enhanced knowledge of the mechanism by which α-glucosidase binds to imino sugars. *

Diabetes Diabetes mellitus, commonly known as diabetes, is a group of common endocrine diseases characterized by sustained high blood sugar levels. Diabetes is due to either the pancreas not producing enough of the hormone insulin, or the cells of th ...

Acarbose Acarbose ( INN) is an anti-diabetic drug used to treat diabetes mellitus type 2 and, in some countries, prediabetes. It is a generic sold in Europe and China as Glucobay ( Bayer AG), in North America as Precose ( Bayer Pharmaceuticals), and in ...

, an α-glucosidase inhibitor, competitively and reversibly inhibits

α-glucosidase In biochemistry, glycoside hydrolases (also called glycosidases or glycosyl hydrolases) are a class of enzymes which catalyze the hydrolysis of glycosidic bonds in complex sugars. They are extremely common enzymes, with roles in nature includi ...

in the intestines. This inhibition lowers the rate of glucose absorption through delayed carbohydrate digestion and extended digestion time. Acarbose may be able to prevent the development of diabetic symptoms. Hence, α-glucosidase inhibitors (like acarbose) are used as anti-diabetic drugs in combination with other anti-diabetic drugs. Luteolin has been found to be a strong inhibitor of α-glucosidase. The compound can inhibit the enzyme up to 36% with a concentration of 0.5 mg/ml. As of 2016, this substance is being tested in rats, mice and cell culture. Flavonoid analogues have been demonstrated with inhibition activity. *

Azoospermia Azoospermia is the medical condition of a man whose semen contains no sperm. It is associated with male infertility, but many forms are amenable to medical treatment. In humans, azoospermia affects about 1% of the male population and may be see ...

: Diagnosis of azoospermia has potential to be aided by measurement of α-glucosidase activity in seminal plasma. Activity in the seminal plasma corresponds to the functionality of the epididymis. * Antiviral agents: Many animal viruses possess an outer envelope composed of viral glycoproteins. These are often required for the viral life cycle and utilize cellular machinery for synthesis. Inhibitors of α-glucosidase show that the enzyme is involved in the pathway for ''N''-glycans for viruses such as HIV and human hepatitis B virus (HBV). Inhibition of α-glucosidase can prevent fusion of HIV and secretion of HBV.

References

{{DEFAULTSORT:Alpha-Glucosidase EC 3.2.1 de:Maltase-Glucoamylase