{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nPancreatic α‐amylase, encoded by AMY2A, is essential for the hydrolysis of dietary starch. Its catalytic activity is modulated by a bound chloride ion that helps to correctly position catalytic residues and fine‐tune their pKa values, ensuring effective enzyme–substrate complex formation. In addition, AMY2A exhibits a specific carbohydrate binding activity by interacting with N‐linked glycan motifs on the brush border membrane, which in turn can activate its own function as well as that of other glycoside hydrolases, insights that have even guided the development of novel oligosaccharide‐based inhibitors."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "3"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its biochemical function, AMY2A‐mediated starch digestion has broad implications for energy homeostasis and metabolism. Variations in copy number and specific genetic variants that affect amylase activity have been linked with differences in weight loss and adiposity, indicating that higher pancreatic amylase levels may facilitate more efficient carbohydrate metabolism. Moreover, circulating amylase levels exhibit associations with regulatory peptides such as ghrelin and peptide YY, highlighting potential roles in appetite control and adaptations to high‐starch diets, especially in populations with traditionally carbohydrate‐rich diets."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "4", "end_ref": "7"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nClinically, alterations in AMY2A function are implicated in several disease processes. Loss of AMY2A expression—including homozygous deletions observed in gastric carcinoma cases—suggests that it may play a tumor suppressor role in the gastrointestinal tract. In addition, autoantibodies directed against pancreatic α‐amylase have been proposed as useful diagnostic markers for autoimmune pancreatitis, underscoring an immunological facet to its function. Population‐based studies further reveal polymorphic variations in AMY2A distribution, reflecting both ethnic diversity and potential links to metabolic or immune-mediated disorders."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "8", "end_ref": "13"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Shin Numao, Iben Damager, Chunmin Li, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "Functional regulation of sugar assimilation by N-glycan-specific interaction of pancreatic α-amylase with glycoproteins of duodenal brush border membrane."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M111.314658"}], "href": "https://doi.org/10.1074/jbc.M111.314658"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22584580"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22584580"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Young Jin Tak, Yu Hyeon Yi, Sang Yeoup Lee, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Relationships Between Fasting Serum Amylase and Ghrelin or Peptide YY3-36 Levels in Healthy Men."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Pancreas (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1097/MPA.0000000000000498"}], "href": "https://doi.org/10.1097/MPA.0000000000000498"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26495778"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26495778"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Yoriko Heianza, Dianjianyi Sun, Tiange Wang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Starch Digestion-Related Amylase Genetic Variant Affects 2-Year Changes in Adiposity in Response to Weight-Loss Diets: The POUNDS Lost Trial."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Diabetes (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.2337/db16-1482"}], "href": "https://doi.org/10.2337/db16-1482"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28659346"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28659346"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Miguel Vázquez-Moreno, Aurora Mejía-Benítez, Tanmay Sharma, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Association of AMY1A/AMY2A copy numbers and AMY1/AMY2 serum enzymatic activity with obesity in Mexican children."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Pediatr Obes (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/ijpo.12641"}], "href": "https://doi.org/10.1111/ijpo.12641"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32314532"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32314532"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Davide Bolognini, Alma Halgren, Runyang Nicolas Lou, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Recurrent evolution and selection shape structural diversity at the amylase locus."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nature (2024)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41586-024-07911-1"}], "href": "https://doi.org/10.1038/s41586-024-07911-1"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "39232174"}], "href": "https://pubmed.ncbi.nlm.nih.gov/39232174"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Sofia Baltova, Hans-Georg Scheil "}, {"type": "b", "children": [{"type": "t", "text": "Population genetic studies of the pancreatic amylase (AMY2, E.C. 3.2.1.1) in Bulgaria."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Coll Antropol (2004)"}]}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15571103"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15571103"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "H G Scheil, H D Schmidt, L Efremovska, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Phenotype and allele frequencies of some serum protein polymorphisms in populations of the Balkans."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Anthropol Anz (2004)"}]}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15648851"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15648851"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Sofia D Baltova "}, {"type": "b", "children": [{"type": "t", "text": "On the genetic polymorphism of the serum alpha-amylase in the population of the south western Bulgaria (second communication)."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Folia Med (Plovdiv) (2005)"}]}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16152770"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16152770"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Toyoshi Endo, Soichi Takizawa, Shoichiro Tanaka, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Amylase alpha-2A autoantibodies: novel marker of autoimmune pancreatitis and fulminant type 1 diabetes."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Diabetes (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.2337/db08-0493"}], "href": "https://doi.org/10.2337/db08-0493"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19001184"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19001184"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Ji Un Kang, Sun Hoe Koo, Kye Chul Kwon, et al. "}, {"type": "b", "children": [{"type": "t", "text": "AMY2A: a possible tumor-suppressor gene of 1p21.1 loss in gastric carcinoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Int J Oncol (2010)"}]}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20428766"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20428766"}]}, {"type": "r", "ref": 13, "children": [{"type": "t", "text": "María Sánchez Castañón, Valeria Zuliani, Antonio Amodio, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Role of Amylase-α2A Autoantibodies in the Diagnosis of Autoimmune Pancreatitis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Pancreas (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1097/MPA.0000000000000417"}], "href": "https://doi.org/10.1097/MPA.0000000000000417"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26335011"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26335011"}]}]}]}