brush border enzymes

**Location and function** - Integral membrane proteins on the apical microvilli of enterocytes, which form the "brush border" and greatly increase surface area. They are most active in the duodenum and jejunum. - They carry out terminal (membrane) digestion after luminal digestion by salivary/pancreatic amylase and pancreatic proteases.

**Key enzymes and substrates** - **Lactase**: lactose → glucose + galactose. - **Sucrase-isomaltase**: sucrose → glucose + fructose. Isomaltase (α-dextrinase) cleaves α-1,6 bonds in limit dextrins. - **Maltase-glucoamylase**: maltose and α-1,4 oligosaccharides → glucose. - **Trehalase**: trehalose (in mushrooms) → 2 glucose. - **Aminopeptidases, dipeptidases, carboxypeptidases**: oligopeptides → amino acids and di-/tripeptides. - **Enteropeptidase (enterokinase)**: trypsinogen → trypsin, which then activates other pancreatic zymogens. This is the key activation step of the pancreatic protease cascade. - **Alkaline phosphatase**: a brush border marker enzyme. **Folate conjugase** (glutamate carboxypeptidase II) cleaves polyglutamate folate to monoglutamate.

**Absorption of products** - Glucose and galactose enter via SGLT1 (Na⁺-dependent, secondary active transport). Fructose enters via GLUT5 (facilitated diffusion). - All three monosaccharides exit the basolateral side via GLUT2. - Di-/tripeptides enter via PepT1 (H⁺-coupled). Amino acids enter via Na⁺-dependent transporters.

**Clinical correlations** - **Lactase deficiency (lactose intolerance)** - *Primary (adult-type)*: lactase persistence declines after weaning. It is the most common form and is more prevalent in people of Asian, African, and Native American descent. - *Secondary*: villous injury from celiac disease, gastroenteritis (rotavirus, Giardia), Crohn disease, or radiation or chemotherapy. - *Congenital*: rare. - *Findings*: bloating, flatulence, and watery osmotic diarrhea after dairy. Stool pH is low (<5.5) from bacterial fermentation, and stool contains reducing substances. The lactose hydrogen breath test is positive. Normal intestinal biopsy in primary deficiency. Treatment is dietary lactose avoidance or lactase supplements. - **Congenital sucrase-isomaltase deficiency**: autosomal recessive. Presents with diarrhea after sucrose or starch is introduced. - **Celiac disease**: villous blunting and loss of brush border cause a secondary, generalized reduction in disaccharidase activity. Lactase is typically affected first. - **Enteropeptidase deficiency**: rare. Causes failure to thrive, diarrhea, and hypoproteinemia or edema in infancy because of impaired protein digestion. - **Pharmacology**: acarbose and miglitol are α-glucosidase inhibitors that block brush border α-glucosidases. This delays carbohydrate absorption and blunts postprandial glucose. Side effects are flatulence and diarrhea. Use oral glucose (not sucrose) to treat hypoglycemia in patients on these drugs. - **Related**: abetalipoproteinemia and Hartnup disease affect enterocyte absorption but not brush border hydrolases.

**High-yield pearls** - Brush border enzymes are lost first in villous atrophy, and lactase is usually the first to go. - The D-xylose test checks mucosal absorptive integrity: abnormal in mucosal disease, normal in pancreatic insufficiency. - Pancreatic enzymes act in the lumen. Brush border enzymes act at the membrane surface.