pancreatic amylase

**Function and physiology** - Pancreatic amylase is an endoglycosidase (alpha-amylase). It cleaves internal alpha-1,4 glycosidic bonds of starch, amylose, amylopectin, and glycogen. - It does NOT cleave alpha-1,6 branch points, terminal alpha-1,4 bonds, or beta-1,4 bonds (cellulose). Humans cannot digest cellulose. - Products: maltose, maltotriose, and alpha-limit dextrins (the branched oligosaccharides left over). - Brush-border enzymes finish digestion: alpha-dextrinase (isomaltase) cleaves alpha-1,6 bonds, and maltase and sucrase cleave the remaining disaccharides and trisaccharides. Monosaccharides are then absorbed. Glucose and galactose enter via SGLT1, and fructose enters via GLUT5. All three exit the enterocyte via GLUT2. - Salivary amylase (ptyalin) begins starch digestion in the mouth, but gastric acid inactivates it. Pancreatic amylase does most of the luminal starch digestion. - Cofactors: it requires Ca2+ and Cl- for activity. Optimal pH is about 7, and bicarbonate-rich pancreatic secretion neutralizes gastric acid to provide this. - Regulation: CCK (from I cells) stimulates acinar enzyme secretion. Secretin (from S cells) stimulates ductal bicarbonate secretion. ACh via vagal M3 signaling also stimulates acinar secretion. - Unlike the proteases, amylase is secreted in its ACTIVE form, not as a zymogen. Trypsinogen, chymotrypsinogen, proelastase, and procarboxypeptidase are secreted as inactive precursors, and enteropeptidase activates trypsinogen.

**Clinical significance** - Acute pancreatitis: diagnosed with 2 of 3 criteria: epigastric pain radiating to the back, serum amylase or lipase >3x the upper limit of normal, and characteristic imaging. Common causes are gallstones and alcohol (also hypertriglyceridemia, hypercalcemia, ERCP, and drugs). Lipase is more sensitive and specific and stays elevated longer. Amylase rises within hours and falls within days. Level of elevation does not correlate with severity. - Other causes of high amylase: - Salivary gland disease (mumps, parotitis, sialolithiasis) - Bowel obstruction or ischemia, and perforated ulcer - Ectopic pregnancy and ovarian tumors - Macroamylasemia - Renal insufficiency (decreased clearance) - Small cell lung cancer (ectopic production) - Eating disorders such as bulimia (salivary isoamylase) - Chronic pancreatitis and pancreatic insufficiency: amylase and lipase may be normal or low late in disease because of acinar destruction. Presentation includes steatorrhea, fat-soluble vitamin deficiency, and diabetes. Treat with pancreatic enzyme replacement. - Cystic fibrosis: thick secretions obstruct pancreatic ducts, causing exocrine insufficiency, with malabsorption and fat-soluble vitamin (A, D, E, K) deficiency. - Pharmacology: acarbose and miglitol are alpha-glucosidase inhibitors that block brush-border enzymes, not amylase itself. They delay carbohydrate absorption, blunt postprandial glucose, and cause flatulence and diarrhea. Pancrelipase is a combination of amylase, lipase, and protease. - Malabsorption: carbohydrate malabsorption causes osmotic diarrhea, bloating, and gas from bacterial fermentation. Lactase deficiency is the more common cause and is a brush-border problem, not a pancreatic one.

**High-yield pearls** - Amylase is an endoenzyme (internal bonds) and the main product is maltose. - Lipase is preferred over amylase for diagnosing acute pancreatitis. - Amylase is the only major pancreatic digestive enzyme secreted in active form besides lipase. Lipase and colipase are also active, and colipase helps lipase act in the presence of bile salts. - Amylase is small enough to be filtered by the kidney, so urinary amylase can be elevated. Macroamylasemia causes high serum amylase with low urinary amylase.