Properties of Pancreatic Juice
Pancreatic juice is a colorless fluid produced by acinar pancreatocytes. Its most crucial physicochemical property is a strongly alkaline reaction (pH 7.8–8.4).
The alkalinity is maintained by an extremely high concentration of bicarbonates (up to 150 mmol/L). Their primary physiological task is the rapid and effective neutralization of the acidic gastric chyme. Without this process, pancreatic enzymes could not function under optimal conditions. Outside of digestion, in the fasting state, the juice is secreted periodically, strictly synchronized with the interdigestive migrating motor complex of the gastrointestinal tract.
Enzyme Activation Cascade
The pancreas synthesizes enzymes for carbohydrate, lipid, and nucleic acid digestion directly in an active state (amylase, lipase, nucleases). However, proteolytic enzymes that break down proteins are secreted as safe proenzymes (zymogens) to prevent autodigestion of the organ.
Digestion is triggered by the activation of trypsin.
- Inactive trypsinogen enters the intestinal lumen, where it encounters enteropeptidase (enterokinase). This activating enzyme, discovered in the laboratory of I.P. Pavlov, is secreted by the intestinal mucosa and is itself preliminarily activated by duodenase.
- Enteropeptidase cleaves a hexapeptide from trypsinogen, converting it into active trypsin (the process is accelerated in the presence of calcium ions).
- An autocatalytic reaction ensues: the newly formed trypsin begins to independently activate the remaining trypsinogen.
- Subsequently, trypsin activates all other proteases: chymotrypsinogen is converted to chymotrypsin, procarboxypeptidases into carboxypeptidases A and B, and proelastase into elastase. Trypsin is also necessary for the activation of prophospholipase.
Protein Digestion: Endo- and Exopeptidases
Enzymatic protein hydrolysis occurs in two major stages involving different classes of proteases.
Endopeptidases act in the stomach and duodenum. They cleave internal peptide bonds of polypeptide chains, breaking them down into oligopeptidases. These include:
- Pepsin: operates in the stomach, preferring bonds adjacent to aromatic and hydrophobic amino acids (e.g., phenylalanine and leucine).
- Trypsin: operates in the intestine, specific to basic amino acids (arginine and lysine).
- Chymotrypsin: cleaves bonds adjacent to aromatic amino acids (tyrosine and phenylalanine).
- Elastase (pancreatopeptidase).
Exopeptidases complete digestion in the small intestine by sequentially cleaving single amino acids from the ends of molecules:
- Aminopeptidases work from the N-terminus (amino group).
- Carboxypeptidases work from the C-terminus (carboxyl group).
- Dipeptidases hydrolyze the remaining bond in dipeptides, converting them into two free amino acids.
Digestion of Carbohydrates, Lipids, and Nucleic Acids
In addition to proteins, pancreatic juice effectively breaks down other macronutrients:
- Carbohydrates: active $\alpha$-amylase digests polysaccharides (starch and glycogen) down to mono- and disaccharides. The enzyme maltase breaks down the disaccharide maltose into glucose.
- Lipids: pancreatic lipase hydrolyzes fats into monoglycerides and fatty acids. Colipase, calcium ions, and bile (bile acid salts) are critically important for enhancing lipid hydrolysis. Esterase and phospholipase A also participate in the process.
- Nucleic acids: ribonuclease digests RNA, and deoxyribonuclease breaks down DNA.
Regulation and Phases of Secretion
Following food intake, juice secretion begins after a short latent period — 3 to 5 minutes. Secretion is finely adapted to the type of food ingested. For example, with a carbohydrate load (bread), the secretion peak is recorded at the 1st hour; with protein (meat), at the 2nd hour; and with milk, at the 3rd hour.
The process is controlled by neural and humoral mechanisms that either directly affect pancreatocytes or operate through regulatory peptides and autonomic nervous system centers. There are four phases of regulation:
- Complex reflex (cephalic).
- Gastric.
- Intestinal.
- Circulatory (an additional phase of humoral correction of pancreatic function via nutrients already absorbed into the blood).