General Characteristics and Stages of Digestion
The biochemical essence of protein digestion is their successive hydrolysis into free amino acids. This process is carried out by enzymes from the peptide hydrolase (peptidase) class, which are secreted by cells of the stomach, pancreas, and intestine.
The process starts in the gastric lumen and includes two key events:
- Protein denaturation. The acidic environment disrupts the complex spatial structure of dietary proteins, making peptide bonds accessible to enzymatic attack.
- Initial hydrolysis. Large protein molecules are cleaved into smaller fragments — oligopeptides.
Subsequently, these oligopeptides enter the small intestine. There, during luminal digestion, pancreatic enzymes break them down into di- and tripeptides. Final hydrolysis into free amino acids and their absorption occur during membrane (juxtaluminal/brush border) digestion, including inside enterocytes themselves.
Role of Hydrochloric Acid and Acidity Assessment
Gastric juice normally has a strongly acidic reaction (pH 1.5–2.0). This environment is due to the secretion of hydrochloric acid (HCl), which performs critical physiological functions. First, it is responsible for the denaturation of dietary proteins and exhibits a potent bactericidal effect. Second, HCl triggers the activation of the zymogen pepsinogen and creates the optimal pH optimum for the resulting active pepsin.
In clinical practice, gastric juice acidity is measured in titration units (TU). The analysis is performed by titrating 100 mL of gastric juice with a 0.1 M sodium hydroxide (NaOH) solution. The following parameters are distinguished:
- Total acidity (normal range 40–60 TU) — the sum of all acid-reacting compounds in a one-hour secretion sample.
- Free hydrochloric acid (normal range 20–40 TU) — HCl molecules not bound to other substances.
- Bound hydrochloric acid (normal range 20–30 TU) — HCl molecules bound to proteins and their hydrolysis products.
Pepsin Specificity and Intestinal Peptidases
The gastric enzyme pepsin has strict substrate specificity. It primarily hydrolyzes peptide bonds involving the amino or carboxyl group of aromatic amino acids. In particular, it cleaves protein regions near Phenylalanine (Phe) and Tyrosine (Tyr). Another target of pepsin is the bond between Leucine and Glutamate (Leu–Glu).
Beyond the stomach, in the small intestine, work continues via pancreatic enzymes, among which exopeptidases stand out — carboxypeptidases A and B.
- They are synthesized as inactive proenzymes (procarboxypeptidases A, B) and are activated by trypsin.
- Their task is to cleave amino acids from the C-terminus of the peptide chain via the mechanism: —X—NH—CH(R)—COOH.
- Carboxypeptidase A is specific for amino acids with a hydrophobic side chain.
- Carboxypeptidase B cleaves Lysine (Lys) or Arginine (Arg) residues.
Mucosal Protective Factors
Despite the presence of aggressive hydrochloric acid and the active proteolytic enzyme pepsin, gastric cells normally do not undergo autodigestion. The mucosa is reliably protected by three barrier mechanisms:
- Mucus. The epithelium is coated with a dense secretion containing heteropolysaccharides. They possess high chemical resistance and are completely unreactive to peptide hydrolases.
- Bicarbonate (HCO₃⁻) secretion. Epithelial cells continuously secrete bicarbonates, forming a buffer zone with a pH of 5.0–6.0 in the unstirred mucus layer. In this less acidic environment, pepsin is inactive, preventing membrane damage.
- Regeneration. Epithelial cells have a high capacity for rapid division and repair of damaged areas.