Enzymes of the Small Intestine

Enzymes of the Small Intestine

6 min read Updated Mar 26, 2026

The small intestine is where the heavy enzymatic machinery lives. Two sources supply the enzymes: the pancreas (secreted into the lumen) and the brush border of the intestinal epithelium itself. Together, they finish the digestion of every macromolecule into its absorbable building blocks.

Pancreatic Enzymes: The Heavy Artillery

The exocrine pancreas produces a cocktail of digestive enzymes delivered to the duodenum through the pancreatic duct. These enzymes work at a slightly alkaline pH (~7-8), which is maintained by pancreatic bicarbonate that neutralizes the acidic chyme from the stomach.

The Trypsin Activation Cascade

This is one of the most important enzyme cascades for the MCAT. All pancreatic proteases are secreted as inactive zymogens to prevent the pancreas from digesting itself.

The cascade works like a row of dominoes:

  1. Enteropeptidase (also called enterokinase) - an enzyme embedded in the duodenal brush border - cleaves trypsinogen into active trypsin
  2. Trypsin then activates everything else:
    • Chymotrypsinogen → chymotrypsin
    • Procarboxypeptidase → carboxypeptidase
    • Proelastase → elastase
    • More trypsinogen → trypsin (autocatalysis)

Complete Pancreatic Enzyme Table

EnzymeZymogen FormSubstrateProducts
TrypsinTrypsinogenProteins/peptidesShorter peptides (cleaves after Arg, Lys)
ChymotrypsinChymotrypsinogenProteins/peptidesShorter peptides (cleaves after Phe, Trp, Tyr)
Carboxypeptidase A & BProcarboxypeptidasePeptidesRemoves C-terminal amino acids
ElastaseProelastaseElastin, proteinsShorter peptides
Pancreatic amylase(secreted active)Starch, glycogenMaltose, maltotriose, limit dextrins
Pancreatic lipase(active form secreted)Triglycerides2 fatty acids + 1 monoglyceride
Nucleases(secreted active)DNA, RNANucleotides

Note that amylase, lipase, and nucleases are secreted in their active forms - they are not zymogens. Only the proteases need to be secreted as zymogens because only proteases pose a self-digestion risk.

Brush-Border Enzymes: The Finishing Touches

Brush-border enzymes are embedded in the microvilli membrane of enterocytes throughout the small intestine. They perform the final digestion steps, breaking dimers and short chains into individual monomers ready for absorption.

Disaccharidases

EnzymeSubstrateProducts
MaltaseMaltoseGlucose + glucose
IsomaltaseIsomaltose (alpha-1,6 branch points)Glucose
SucraseSucroseGlucose + fructose
LactaseLactoseGlucose + galactose

Peptidases

EnzymeSubstrateProducts
AminopeptidasePeptidesRemoves N-terminal amino acid
DipeptidaseDipeptidesTwo free amino acids

Other Brush-Border Enzymes

  • Enteropeptidase - converts trypsinogen to trypsin (the cascade starter)
  • Nucleotidases and nucleosidases - break nucleotides into bases, sugars, and phosphate groups

The Complete Digestion Summary

Flowchart showing protein digestion from stomach through small intestine, with pepsin cleaving proteins into peptides and then pancreatic proteases and brush-border peptidases producing amino acids
Protein digestion pathway: pepsin starts in the stomach, then trypsin, chymotrypsin, and brush-border peptidases finish the job in the small intestine. Credit: OpenStax Anatomy and Physiology 2e, CC BY 4.0
MacromoleculeMouthStomachSmall IntestineFinal Products
StarchSalivary amylase(paused - too acidic)Pancreatic amylase, then maltase/sucrase/lactaseMonosaccharides
ProteinNonePepsinTrypsin, chymotrypsin, carboxypeptidase, aminopeptidase, dipeptidaseAmino acids
FatLingual lipaseGastric lipaseBile + pancreatic lipaseFatty acids + monoglycerides
Nucleic acidsNoneNoneNucleases, nucleotidases, nucleosidasesBases + sugars + phosphate
If enteropeptidase were deficient, which pancreatic enzymes would remain inactive?
Click to reveal answer
ALL pancreatic proteases would remain inactive. Enteropeptidase activates trypsinogen to trypsin. Trypsin activates chymotrypsinogen, procarboxypeptidase, and proelastase. Without enteropeptidase, no trypsin is formed, so the entire protease cascade fails. Pancreatic amylase and lipase are unaffected (they are secreted in active form).
A patient has severe chronic pancreatitis with almost no pancreatic enzyme output. Which macromolecule digestion would be MOST impaired?
Click to reveal answer
Fat digestion. While protein digestion can partially occur in the stomach (pepsin) and carbohydrate digestion starts in the mouth (salivary amylase), fat digestion relies almost entirely on pancreatic lipase (plus bile). Lingual and gastric lipase handle only 10-30% of fat digestion. Without pancreatic lipase, most dietary fat passes through unabsorbed, causing steatorrhea (fatty stools).