Digestive enzymes
Enzymes that could digest you, boxed up until needed.
Macromolecules in, monomers out. Every protease shipped as a zymogen
This mnemonic, unpacked word by word →
The gut's central problem is that its best tools would digest their own maker, so every protease ships as an inactive zymogen and is armed only on site: pepsinogen by stomach acid, trypsinogen by the brush border's enteropeptidase, and trypsin then arms everything else, an amplification cascade with one master switch. Premature firing inside the pancreas is pancreatitis.
Digestion starts before swallowing: why bread turns faintly sweet if you chew long enough. Stomach acid inactivates it; the pancreatic version finishes the job downstream.
Gastrin orders the parietal cells to pump HCl, and the same parietal cells make intrinsic factor, the B₁₂ chaperone. Autoimmune loss of these cells is pernicious anemia.
The acid does two jobs: it unfolds dietary proteins and clips pepsinogen into pepsin, which then activates more pepsinogen itself. First lesson of the gut: never store an active protease.
Secretin answers the acid with pancreatic bicarbonate, lifting the pH toward 8, the room trypsin needs. CCK answers fats and peptides with pancreatic enzymes and a squeeze of the gallbladder.
The master switch, deliberately located OUTSIDE the pancreas. If trypsin activates early, inside the gland, it digests the pancreas itself: pancreatitis. A dedicated trypsin inhibitor travels in the pancreatic juice as insurance.
Trypsin activates many targets at once, the same amplification logic as the PKA cascade, built from scissors. Division of labor: trypsin cuts after K and R, chymotrypsin after the aromatics, carboxypeptidases chew in from the ends.
Bile salts are a detergent with no enzyme activity of their own: they break fat into droplets so lipase has surface to work on. No bile, no absorption: fat sails through, taking the fat-soluble vitamins (A, D, E, K) with it.
The last cut happens on the enterocyte surface, and only monomers are absorbed. Lose lactase, as most adults worldwide do, and lactose stays in the lumen, pulling in water and feeding gas-producing bacteria: lactose intolerance. Upstream in the duodenum, iron and calcium, the "FeCal duo", were absorbed first.