brush border enzyme

**Definition/Location:** Membrane-bound ectoenzymes on the apical microvilli (brush border) of enterocytes, highest in the duodenum and jejunum. Villi/microvilli greatly increase surface area. Enzymes are synthesized in enterocytes and inserted into the apical membrane; they are lost as enterocytes are shed (turnover ~3–5 days), so damage to villi reduces enzyme activity.

**Key enzymes and functions:** - **Lactase** (β-galactosidase): lactose → glucose + galactose - **Sucrase-isomaltase:** sucrose → glucose + fructose; isomaltose/α-limit dextrins → glucose - **Maltase (maltase-glucoamylase):** maltose/maltotriose → glucose - **Trehalase:** trehalose → glucose (mushrooms) - **α-Dextrinase (isomaltase):** cleaves α-1,6 branch points - **Aminopeptidases, dipeptidases, carboxypeptidases:** oligopeptides → free amino acids, di- and tripeptides (absorbed via PepT1) - **Enteropeptidase (enterokinase):** activates trypsinogen → trypsin, which then activates other pancreatic zymogens (key link between brush border and pancreatic digestion) - **Alkaline phosphatase:** brush border marker, also clinically used (ALP) - Folate conjugase (folate deconjugase) cleaves polyglutamate folate for absorption in the jejunum

**Carbohydrate absorption:** Pancreatic and salivary α-amylase produce oligosaccharides; brush border enzymes then produce monosaccharides. Glucose and galactose enter via SGLT-1 (Na⁺-dependent); fructose via GLUT-5 (facilitated diffusion). All exit the basolateral side via GLUT-2.

**Clinical correlations:** - **Lactase deficiency (lactose intolerance):** Most common. Primary (adult-onset, genetic downregulation of lactase persistence) or secondary (gastroenteritis, celiac disease, Crohn disease, giardiasis, rotavirus, malnutrition). Undigested lactose is osmotically active and fermented by colonic bacteria → watery diarrhea, bloating, flatulence, cramps (H₂, short-chain fatty acids). Stool pH is low (<5.5); breath hydrogen test positive; normal intestinal biopsy in primary form. Treat with lactose avoidance or lactase supplement. - **Congenital sucrase-isomaltase deficiency:** Presents after sucrose/starch introduction; osmotic diarrhea. - **Celiac disease, tropical sprue, and other causes of villous atrophy:** Loss of brush border surface area → decreased enzyme activity (secondary lactase deficiency often first) and malabsorption. - **Enteropeptidase deficiency:** Rare; failure to thrive, diarrhea, hypoproteinemia/edema due to impaired protein digestion. - **Acarbose/miglitol (α-glucosidase inhibitors):** Inhibit brush border α-glucosidases to reduce postprandial glucose in type 2 diabetes. Adverse effects: flatulence, diarrhea, abdominal discomfort. Hypoglycemia treatment in patients taking these requires glucose (not sucrose) since sucrase is inhibited. - **Hartnup disease and cystinuria** involve brush border amino acid transporters (not enzymes), commonly confused on exams. - **Abetalipoproteinemia/other malabsorption** affect lipid handling, not brush border enzymes per se.

**High-yield pearls:** Lactase is the most distal/"last to develop and first to be lost" with mucosal injury. Brush border enzymes complete digestion of the products of luminal (pancreatic/salivary) digestion. Osmotic diarrhea resolves with fasting (vs secretory diarrhea) and has an increased stool osmotic gap.