Questions: Intestinal Absorption and Nutrient Transport

Question 1

A drug blocks the Na⁺/K⁺-ATPase on the basolateral membrane of intestinal enterocytes. Which nutrient's absorption would be most directly impaired?

• A. Fructose, because it requires sodium cotransport to cross the apical membrane
• B. Dietary fat, because micelle formation depends on the sodium gradient
• C. Glucose, because its apical transport via SGLT1 is driven by the sodium gradient maintained by Na⁺/K⁺-ATPase
• D. All nutrients equally, because the Na⁺/K⁺-ATPase powers the general absorptive machinery

Answer: (C)

SGLT1 (the glucose/galactose transporter on the apical membrane) is a secondary active transporter: it uses the sodium electrochemical gradient as its energy source, pulling glucose into the cell as sodium flows down its gradient. The Na⁺/K⁺-ATPase on the basolateral side maintains this sodium gradient by continuously pumping sodium out of the cell. Block the ATPase, sodium accumulates inside, the gradient collapses, and SGLT1 can no longer drive glucose uptake against its concentration gradient. Fructose uses GLUT5 (facilitated diffusion, no sodium required) and would be largely unaffected. Fat absorption is passive and also unaffected.

Question 2

Why do absorbed dietary fats enter the lymphatic system (via lacteals) rather than flowing directly into blood capillaries like glucose and amino acids?

• A. Fat is chemically incompatible with blood plasma and would cause clotting if it entered directly
• B. Chylomicrons are too large to cross the basement membrane of blood capillaries, but can enter the more permeable lacteals
• C. The portal vein cannot transport lipids, so an alternative route to the liver is needed
• D. Fat-soluble vitamins require a low-oxygen environment that only the lymphatics provide

Answer: (B)

After reassembly in the smooth endoplasmic reticulum, triglycerides are packaged into chylomicrons — lipoprotein particles that are too large (typically 75–1200 nm diameter) to squeeze through the tight junctions and basement membranes of blood capillaries. Lacteals, the lymphatic capillaries within intestinal villi, have loose junctions and a more permeable structure that allows chylomicrons to enter. The chylomicron-laden lymph travels through the thoracic duct and empties into the bloodstream at the subclavian vein. This is why fatty meals temporarily produce a milky-white lymph (chyle) in the lacteals.

Question 3

Fructose absorption has a lower intestinal capacity than glucose absorption because fructose uses facilitated diffusion (GLUT5) rather than active transport (SGLT1).

• T. True
• F. False

Answer: True

Active transport via SGLT1 can move glucose against its concentration gradient, maintaining a steep inward gradient regardless of how much glucose is already inside the cell. Facilitated diffusion via GLUT5 can only move fructose down its concentration gradient, and transport rate plateaus once the concentration gradient is small. This capacity difference explains why excessive fructose intake can overwhelm the system, with unabsorbed fructose reaching the colon where it is fermented by bacteria — producing gas, osmotic water pull, and diarrhea.

Question 4

Dietary fat is absorbed into the bloodstream in the same way as glucose — by crossing the intestinal epithelium and entering capillaries in the intestinal villi.

• T. True
• F. False

Answer: False

The paths are fundamentally different. Glucose is a small, water-soluble molecule that crosses the apical membrane via SGLT1, moves through the enterocyte, exits via GLUT2 on the basolateral side, and enters blood capillaries directly. Fat is hydrophobic and must be solubilized by bile salts into micelles before it can approach the brush border. Once absorbed, fatty acids are reassembled into triglycerides, packaged into chylomicrons in the smooth ER, and secreted into lacteals (lymphatic capillaries) — not blood capillaries. Chylomicrons eventually reach the blood via the thoracic duct, bypassing the portal circulation entirely.

Question 5

Why does blocking the sodium gradient impair glucose absorption but not fructose absorption, even though both are monosaccharides absorbed by the same enterocytes?

Model answer: Glucose and galactose cross the apical membrane via SGLT1, a secondary active transporter that couples glucose uptake to the flow of sodium ions down their electrochemical gradient. This gradient is maintained by the Na⁺/K⁺-ATPase pumping sodium out of the cell. If the gradient is disrupted, SGLT1 cannot function and glucose cannot be actively absorbed. Fructose, by contrast, uses GLUT5 — a facilitated diffusion transporter that requires no sodium and no energy source beyond the fructose concentration gradient itself. Disrupting the sodium gradient leaves GLUT5 fully functional and fructose absorption unaffected.

This contrast illustrates that transport mechanism is determined by the transporter's biochemistry, not by the nutrient category. Two monosaccharides with similar molecular size can use fundamentally different transport systems with different energy requirements and regulatory properties — a key principle of membrane transport physiology.