Enzymes Involved in Digestion

Why This Matters

Digestive enzymes are the molecular workhorses that transform the food you eat into nutrients your cells can actually use. You're not just memorizing a list of enzymes here—you're learning how the body orchestrates a precise sequence of chemical reactions, each enzyme activated at exactly the right time, in exactly the right pH environment, to break specific chemical bonds. This connects directly to concepts you'll see tested: enzyme specificity, pH optimization, zymogen activation, and the coordination between digestive organs.

When exam questions ask about digestion, they're really testing whether you understand substrate specificity (why lipase won't touch proteins), activation cascades (why pepsinogen must become pepsin), and structural adaptations (why brush border enzymes sit exactly where absorption happens). Don't just memorize what each enzyme does—know why it works where it does and how it connects to the bigger picture of nutrient absorption.

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Protein-Digesting Enzymes (Proteases)

Protein digestion requires multiple enzymes working in sequence because proteins are large, complex molecules with thousands of peptide bonds. Each protease targets specific amino acid sequences, progressively reducing proteins to absorbable amino acids.

Pepsin

• Only protease active in the stomach—initiates protein digestion by cleaving proteins into large polypeptides
• Activated from pepsinogen by hydrochloric acid; this zymogen activation prevents the enzyme from digesting stomach cells
• Optimal pH of 1.5–2.0 makes it one of the few enzymes that functions in highly acidic conditions

Trypsin

• Master activator of the small intestine—not only digests proteins but activates other pancreatic zymogens including chymotrypsinogen
• Activated from trypsinogen by enterokinase (also called enteropeptidase), a brush border enzyme
• Optimal pH of 7.5–8.5 reflects the alkaline environment created by pancreatic bicarbonate secretion

Chymotrypsin

• Cleaves peptide bonds at aromatic amino acids—specifically targets phenylalanine, tyrosine, and tryptophan residues
• Activated from chymotrypsinogen by trypsin—demonstrates the enzyme activation cascade in the small intestine
• Works synergistically with trypsin to break proteins at different sites, increasing digestion efficiency

Peptidases

• Complete the final step of protein digestion—convert dipeptides and tripeptides into individual amino acids
• Located in the brush border membrane—positioning allows immediate absorption of amino acid products
• Include dipeptidases and aminopeptidases—each type targets specific peptide lengths or terminal amino acids

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Carbohydrate-Digesting Enzymes

Carbohydrate digestion breaks polysaccharides and disaccharides into monosaccharides—the only form that can cross the intestinal epithelium. This process begins in the mouth, pauses in the stomach, and completes in the small intestine.

Amylase

• Only digestive enzyme active in two locations—salivary amylase begins starch digestion in the mouth; pancreatic amylase continues it in the small intestine
• Breaks $\alpha$-1,4 glycosidic bonds in starch, producing maltose and dextrins
• Inactivated by stomach acid—explains why carbohydrate digestion pauses until food reaches the duodenum

Maltase

• Converts maltose into two glucose molecules—completes the digestion of starch that amylase started
• Brush border enzyme embedded in the microvilli membrane of intestinal epithelial cells
• Deficiency is rare but would impair the final step of starch digestion

Sucrase

• Splits sucrose into glucose and fructose—essential for digesting table sugar and many processed foods
• Brush border location ensures monosaccharide products are immediately available for absorption
• Works alongside maltase and lactase as part of the disaccharidase enzyme family

Lactase

• Hydrolyzes lactose into glucose and galactose—the only enzyme capable of digesting milk sugar
• Expression decreases after weaning in most human populations, leading to lactose intolerance
• Deficiency causes osmotic diarrhea—undigested lactose draws water into the intestinal lumen and is fermented by bacteria

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Lipid-Digesting Enzymes

Fat digestion presents a unique challenge: lipids are hydrophobic and cluster into large droplets that enzymes cannot efficiently access. The solution involves mechanical emulsification by bile followed by enzymatic hydrolysis.

Lipase

• Primary enzyme for triglyceride digestion—cleaves fatty acids from the glycerol backbone
• Requires bile salt emulsification—bile breaks fat globules into smaller micelles, dramatically increasing surface area for lipase action
• Pancreatic lipase is the main form; lingual lipase provides minor fat digestion beginning in the mouth
• Products are fatty acids and monoglycerides—these form mixed micelles that deliver lipids to the brush border for absorption

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Nucleic Acid-Digesting Enzymes

DNA and RNA from food must be broken down into their component nucleotides before absorption. This often-overlooked category completes the picture of macronutrient digestion.

Nucleases

• Pancreatic DNase and RNase hydrolyze nucleic acids into individual nucleotides
• Act in the small intestine alongside other pancreatic enzymes after release from the pancreatic duct
• Nucleotides are further broken down by brush border nucleotidases and nucleosidases into absorbable components (nitrogenous bases, sugars, phosphate)

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Quick Reference Table

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Self-Check Questions

1. Which two proteases are both activated from zymogens but function at opposite pH extremes? What does this tell you about their locations of action?

2. Compare and contrast amylase and maltase: Where does each act, what substrate does each target, and how do they work together to complete starch digestion?

3. If a patient's pancreas is not producing adequate bicarbonate, which enzymes would be most affected and why?

4. A patient presents with bloating and diarrhea after consuming dairy. Which brush border enzyme is likely deficient, and what is the mechanism behind these symptoms?

5. An FRQ asks you to explain why the small intestine contains both secreted enzymes and brush border enzymes. Using specific examples, explain the functional advantage of this arrangement for nutrient absorption.