Fundamental Digestive Enzymes

Why This Matters

Digestive enzymes are the molecular workhorses that transform the food on your plate into absorbable nutrients your cells can actually use. In anatomy and physiology, you're being tested on more than just enzyme names—you need to understand where each enzyme is produced, what substrate it targets, and how activation mechanisms protect tissues from self-digestion. These concepts connect directly to larger themes like chemical digestion vs. mechanical digestion, zymogen activation, and regional specialization of the GI tract.

Don't just memorize that pepsin digests protein—know why it requires an acidic environment, where it becomes active, and how it differs from trypsin working on the same macromolecule in a different location. When exam questions ask you to trace a nutrient from ingestion to absorption, you'll need to identify which enzymes act at each stage and what products they release. Master the underlying principles here, and you'll be ready for both multiple choice and short-answer questions.

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Carbohydrate-Digesting Enzymes

Carbohydrate digestion begins in the mouth and finishes at the brush border of the small intestine. Salivary and pancreatic enzymes handle initial starch breakdown, while brush border enzymes complete the job by splitting disaccharides into absorbable monosaccharides.

Amylase

• Breaks down starch into maltose and dextrins—this is the only chemical digestion that begins in the oral cavity
• Produced in two locations: salivary glands (salivary amylase/ptyalin) and pancreas (pancreatic amylase)
• Optimal pH is neutral to slightly alkaline—salivary amylase is inactivated once food reaches the acidic stomach

Maltase

• Converts maltose into two glucose molecules—completing the digestion of starch that amylase started
• Brush border enzyme located on the microvilli of small intestine enterocytes
• Produces glucose, the body's primary energy currency for cellular respiration via $C_6H_{12}O_6$

Lactase

• Hydrolyzes lactose into glucose and galactose—lactose is the primary sugar in mammalian milk
• Brush border enzyme with activity that often decreases after childhood in many populations
• Clinical relevance: lactase deficiency causes lactose intolerance, resulting in osmotic diarrhea and gas from bacterial fermentation

Sucrase

• Splits sucrose (table sugar) into glucose and fructose—both monosaccharides are then absorbed
• Located on the brush border of the small intestine alongside maltase and lactase
• Works in tandem with other disaccharidases to ensure all dietary sugars reach absorbable form

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Protein-Digesting Enzymes (Proteases)

Protein digestion requires multiple enzymes working in sequence because proteins are large, complex molecules. Proteases are secreted as inactive zymogens to prevent autodigestion of the tissues that produce them—a critical protective mechanism you must understand.

Pepsin

• Digests proteins into large peptide fragments—the only protease active in the stomach
• Secreted as pepsinogen by chief cells and activated by hydrochloric acid (pH 1.5–2) from parietal cells
• Optimal pH is highly acidic—pepsin denatures and becomes inactive when it enters the alkaline small intestine

Trypsin

• Cleaves proteins and peptides at specific amino acid residues (lysine and arginine)
• Secreted as trypsinogen by the pancreas and activated by enterokinase (enteropeptidase) in the duodenum
• Master activator: once active, trypsin activates chymotrypsinogen, procarboxypeptidase, and more trypsinogen (autocatalytic cascade)

Chymotrypsin

• Cleaves proteins at aromatic amino acids (phenylalanine, tyrosine, tryptophan)—complementing trypsin's specificity
• Activated from chymotrypsinogen by trypsin in the small intestine
• Works synergistically with trypsin to break proteins into smaller peptide chains for further digestion

Peptidases

• Hydrolyze small peptides into individual amino acids—the final step before absorption
• Aminopeptidases work from the N-terminus; carboxypeptidases work from the C-terminus
• Located on brush border and within enterocyte cytoplasm—ensuring complete protein breakdown to absorbable units

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Lipid-Digesting Enzymes

Fat digestion presents a unique challenge: lipids are hydrophobic and don't mix with the aqueous environment of the GI tract. Bile salts emulsify fats into smaller droplets, dramatically increasing surface area for lipase to act—this mechanical-chemical partnership is frequently tested.

Lipase

• Hydrolyzes triglycerides into fatty acids and monoglycerides—the absorbable products of fat digestion
• Pancreatic lipase is the primary enzyme; smaller amounts of lingual lipase (mouth) and gastric lipase (stomach) assist
• Requires colipase to anchor it to emulsified fat droplets and bile salts for emulsification—without bile, fat digestion is severely impaired

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Nucleic Acid-Digesting Enzymes

Every cell you eat contains DNA and RNA, which must be broken down into absorbable components. Nucleases reduce nucleic acids to nucleotides, then nucleotidases and nucleosidases complete the breakdown to bases, sugars, and phosphates.

Nucleases

• Break down DNA and RNA into nucleotides—includes DNase and RNase secreted by the pancreas
• Active in the small intestine where pH is optimal for enzymatic function
• Products are further digested by brush border nucleotidases and nucleosidases into absorbable components (pentose sugars, nitrogenous bases, phosphate)

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Quick Reference Table

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Self-Check Questions

1. Which two enzymes are both proteases but require completely different pH environments for activation, and what activates each one?

2. Trace the digestion of a starch molecule from mouth to absorption—which enzymes act on it and what products does each produce?

3. Compare and contrast the activation of pepsinogen versus trypsinogen. Why is the zymogen mechanism essential for preventing tissue damage?

4. A patient has their gallbladder removed. Which macronutrient will they have the most difficulty digesting, and why doesn't this affect carbohydrate or protein digestion?

5. All three brush border disaccharidases (maltase, lactase, sucrase) share a common location and function. What distinguishes them, and which deficiency has the most significant clinical presentation?