Maltase-glucoamylase

MGAM
Available structures PDB Human UniProt search: PDBe RCSB List of PDB id codes 2QLY, 2QMJ, 3CTT, 3L4T, 3L4U, 3L4V, 3L4W, 3L4X, 3L4Y, 3L4Z, 3TON, 3TOP
Identifiers
Aliases	MGAM, MG, MGA, Maltase-glucoamylase
External IDs	OMIM: 154360; MGI: 1203495; HomoloGene: 130099; GeneCards: MGAM; OMA:MGAM - orthologs
Gene location (Human) Chr. Chromosome 7 (human) Band 7q34 Start 141,907,813 bp End 142,106,747 bp
Gene location (Mouse) Chr. Chromosome 6 (mouse) Band 6|6 B1 Start 40,605,765 bp End 40,746,057 bp
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in duodenum blood bone marrow cells spleen right lung granulocyte human kidney monocyte gonad renal cortex Top expressed in jejunum duodenum ileum Paneth cell epithelium of small intestine colon left colon granulocyte migratory enteric neural crest cell human kidney More reference expression data BioGPS n/a
Gene ontology Molecular function hydrolase activity, acting on glycosyl bonds maltose alpha-glucosidase activity hydrolase activity, hydrolyzing O-glycosyl compounds catalytic activity alpha-1,4-glucosidase activity hydrolase activity amylase activity glucan 1,4-alpha-glucosidase activity carbohydrate binding alpha-glucosidase activity Cellular component integral component of membrane plasma membrane apical plasma membrane extracellular exosome membrane tertiary granule membrane ficolin-1-rich granule membrane Biological process polysaccharide digestion metabolism starch catabolic process maltose metabolic process neutrophil degranulation carbohydrate metabolic process Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 8972 232714 Ensembl ENSG00000257335 ENSG00000282607 ENSMUSG00000068587 UniProt O43451 n/a RefSeq (mRNA) NM_004668 NM_001365693 NM_001171003 NM_001368875 RefSeq (protein) NP_004659 NP_001352622 n/a Location (UCSC) Chr 7: 141.91 – 142.11 Mb Chr 6: 40.61 – 40.75 Mb PubMed search
Wikidata
View/Edit Human View/Edit Mouse

Maltase-glucoamylase, intestinal is an enzyme that in humans is encoded by the MGAM gene.

Maltase-glucoamylase is an alpha-glucosidase digestive enzyme. It consists of two subunits with differing substrate specificity. Recombinant enzyme studies have shown that its N-terminal catalytic domain has highest activity against maltose, while the C-terminal domain has a broader substrate specificity and activity against glucose oligomers. In the small intestine, this enzyme works in synergy with sucrase-isomaltase and alpha-amylase to digest the full range of dietary starches.

Gene

The MGAM gene –– which is located on chromosome 7q34 –– codes for the protein Maltase-Glucoamylase. An alternative name for Maltase-Glucoamylase is glucan 1,4-alpha-glycosidase.

Tissue distribution

Maltase-glucoamylase is a membrane-bound enzyme located in the intestinal walls. This lining of the intestine forms brush border in which food has to pass in order for the intestines to absorb the food.

Enzymatic mechanism

This enzyme is a part of a family of enzymes called glycoside hydrolase family 31 (GH31). This is due to the digestive mechanism of the enzyme. GH31 enzymes undergo what is known as the Koshland double displacement mechanism in which a glycosylation and deglycosylation step occurs, resulting in the retention of the overall configuration of the anomeric center.

Structure

N-terminal maltase

The N-terminal maltase-glucoamylase enzymatic unit is in turn composed of 5 specific protein domains. The first of the 5 protein domains consist of a P-type trefoil domain containing a cysteine rich domain. Second is an N-terminal beta-sandwich domain, identified via two antiparallel beta pleated sheets. The third and largest domain consists of a catalytic (beta/alpha) barrel type domain containing two inserted loops. The fourth and 5th domains are C-terminal domains, similar to the N-terminal beta-sandwich domain. The N-terminal Maltase-glucoamylase does not have the +2/+3 sugar binding active sites and so it cannot bind to larger substrates. The N-terminal domain shows its optimal enzymatic affinity for substrates maltose, maltotriose, maltotetrose, and maltopentose.

C-terminal glucase

The C-terminal glucase enzymatic unit contains extra binding sites, which allows for it to bind to larger substrates for catalytic digestion. It was originally understood that maltase-glucoamylase's crystalline structure was inherently similar throughout the N and C-termini. Further studies have found that the C-terminus is composed of 21 more amino acid residues than the N-terminus, which account for its difference in function. Sucrase-Isomaltase –– located on chromosome 3q26–– has a similar crystalline structure to maltase-glucoamylase and work in tandem in the human small intestine. They have been derived from a common ancestor, as they both come from the same GH31 family. As a result of having similar properties, both of these enzymes work together in the small intestine in order to convert consumed starch into glucose for metabolic energy. The difference between these two enzymes is that maltase-glucoamylase has a specific activity at the 1-4 linkage of sugar, where at SI has a specific activity at the 1-6 linkage.

See also

• Alpha-glucosidase
• Maltase

Further reading

• Nichols BL, Avery S, Sen P, Swallow DM, Hahn D, Sterchi E (February 2003). "The maltase-glucoamylase gene: common ancestry to sucrase-isomaltase with complementary starch digestion activities". Proceedings of the National Academy of Sciences of the United States of America. 100 (3): 1432–7. Bibcode:2003PNAS..100.1432N. doi:10.1073/pnas.0237170100. PMC 298790. PMID 12547908.
• Takeshita F, Ishii KJ, Kobiyama K, Kojima Y, Coban C, Sasaki S, et al. (August 2005). "TRAF4 acts as a silencer in TLR-mediated signaling through the association with TRAF6 and TRIF". European Journal of Immunology. 35 (8): 2477–85. doi:10.1002/eji.200526151. PMID 16052631.
• Danielsen EM (October 1987). "Tyrosine sulfation, a post-translational modification of microvillar enzymes in the small intestinal enterocyte". The EMBO Journal. 6 (10): 2891–6. doi:10.1002/j.1460-2075.1987.tb02592.x. PMC 553723. PMID 3121301.
• Korpela MP, Paetau A, Löfberg MI, Timonen MH, Lamminen AE, Kiuru-Enari SM (July 2009). "A novel mutation of the GAA gene in a Finnish late-onset Pompe disease patient: clinical phenotype and follow-up with enzyme replacement therapy". Muscle & Nerve. 40 (1): 143–8. doi:10.1002/mus.21291. PMID 19472353. S2CID 20120101.
• Sim L, Quezada-Calvillo R, Sterchi EE, Nichols BL, Rose DR (January 2008). "Human intestinal maltase-glucoamylase: crystal structure of the N-terminal catalytic subunit and basis of inhibition and substrate specificity". Journal of Molecular Biology. 375 (3): 782–92. doi:10.1016/j.jmb.2007.10.069. PMID 18036614.
• Naim HY, Sterchi EE, Lentze MJ (December 1988). "Structure, biosynthesis, and glycosylation of human small intestinal maltase-glucoamylase". The Journal of Biological Chemistry. 263 (36): 19709–17. doi:10.1016/S0021-9258(19)77693-5. PMID 3143729.
• Ao Z, Quezada-Calvillo R, Sim L, Nichols BL, Rose DR, Sterchi EE, Hamaker BR (May 2007). "Evidence of native starch degradation with human small intestinal maltase-glucoamylase (recombinant)". FEBS Letters. 581 (13): 2381–8. doi:10.1016/j.febslet.2007.04.035. PMID 17485087. S2CID 23891882.
• Tuğrul S, Kutlu T, Pekin O, Bağlam E, Kiyak H, Oral O (October 2008). "Clinical, endocrine, and metabolic effects of acarbose, a alpha-glucosidase inhibitor, in overweight and nonoverweight patients with polycystic ovarian syndrome". Fertility and Sterility. 90 (4): 1144–8. doi:10.1016/j.fertnstert.2007.07.1326. PMID 18377903.

External links

• PDBe-KB provides an overview of all the structure information available in the PDB for Human Maltase-glucoamylase, intestinal