Protein digestion is a complex process that starts in the stomach and finishes in the small intestine. Enzymes like pepsin, trypsin, and chymotrypsin break down proteins into smaller peptides and amino acids. This process is crucial for our bodies to use the proteins we eat.

Once broken down, amino acids are absorbed in the small intestine through various transport systems. Some are actively transported, while others diffuse passively. The liver then processes these amino acids, using them for protein synthesis or breaking them down further for energy.

Protein Digestion in the GI Tract

Stomach Digestion

• Protein digestion initiates in the stomach through pepsin action
• Pepsin activated by hydrochloric acid denatures proteins and cleaves peptide bonds
• Hydrochloric acid creates an acidic environment (pH 1.5-3.5) optimal for pepsin activity
• Pepsin preferentially cleaves peptide bonds adjacent to aromatic amino acids (phenylalanine, tryptophan)

Small Intestine Digestion

• Majority of protein digestion occurs in small intestine, primarily duodenum and jejunum
• Pancreatic proteases (trypsin, chymotrypsin, carboxypeptidases) break down proteins into smaller peptides
• Brush border enzymes (aminopeptidases, dipeptidases) further cleave peptides into individual amino acids and small peptides
• End products of protein digestion consist of free amino acids, di- and tripeptides
• Approximately 50-100 grams of dietary protein digested daily in healthy adults

Enzymes of Protein Digestion

Gastric Enzymes

• Pepsin secreted by chief cells in stomach as inactive pepsinogen
• Hydrochloric acid activates pepsinogen to pepsin through autocatalytic cleavage
• Pepsin optimal activity at low pH (1.5-2.5), becomes inactive at pH above 6.5
• Pepsin cleaves approximately 10-15% of dietary protein bonds in stomach

Pancreatic Enzymes

• Trypsin, chymotrypsin, and elastase secreted by pancreas as inactive zymogens
• Enterokinase, produced by duodenal epithelial cells, activates trypsinogen to trypsin
• Trypsin activation initiates cascade of pancreatic enzyme activation
• Trypsin cleaves peptide bonds after basic amino acids (lysine, arginine)
• Chymotrypsin cleaves after aromatic amino acids (phenylalanine, tyrosine, tryptophan)
• Elastase cleaves after small, neutral amino acids (alanine, glycine, serine)
• Carboxypeptidases A and B remove amino acids from carboxyl terminus of peptides
  • Carboxypeptidase A acts on aromatic and aliphatic amino acids
  • Carboxypeptidase B acts on basic amino acids

Brush Border Enzymes

• Aminopeptidases located on brush border of small intestinal epithelial cells
• Aminopeptidases cleave amino acids from amino terminus of peptides
• Multiple aminopeptidases exist with varying specificities (leucine aminopeptidase, aminopeptidase N)
• Dipeptidases hydrolyze dipeptides into individual amino acids
• Brush border enzymes complete final stages of protein digestion

Amino Acid Absorption in the Small Intestine

Active Transport Mechanisms

• Amino acid absorption primarily occurs in small intestine through active and passive transport
• Several amino acid transport systems exist with varying specificities
• B0 system major sodium-dependent transporter for neutral amino acids
  • Utilizes sodium gradient to drive amino acid uptake
  • Transports amino acids like alanine, serine, and threonine
• ASC system transports small neutral amino acids (alanine, serine, cysteine)
• X-AG system transports acidic amino acids (glutamate, aspartate)
• y+ system transports basic amino acids (lysine, arginine) independent of sodium

Peptide Transport

• Di- and tripeptides absorbed via PEPT1 transporter
• PEPT1 coupled to proton gradient, allowing uphill transport of peptides
• PEPT1 has broad substrate specificity, transporting various di- and tripeptides
• Once inside enterocytes, peptides further hydrolyzed by cytoplasmic peptidases
• Resulting amino acids transported into bloodstream via basolateral transporters

Passive Transport

• Some amino acids absorbed through passive diffusion
• Passive transport more significant at higher luminal concentrations
• Neutral amino acids more likely to be absorbed passively than charged amino acids
• Passive diffusion contributes minimally to overall amino acid absorption

Fate and Transport of Absorbed Amino Acids

Liver Processing

• Absorbed amino acids enter portal circulation and transported to liver
• Liver plays central role in amino acid metabolism
• Liver regulates plasma amino acid levels through various processes
  • Protein synthesis (albumin, clotting factors)
  • Amino acid degradation and interconversion
  • Urea synthesis for nitrogen excretion
• Non-essential amino acids synthesized in liver from other amino acids or metabolic intermediates
• Excess amino acids catabolized in liver, amino groups converted to urea for excretion

Systemic Circulation and Tissue Utilization

• Amino acids not metabolized by liver enter systemic circulation for use by other tissues
• Skeletal muscle major site of amino acid uptake and utilization
  • Particularly important for branched-chain amino acids (leucine, isoleucine, valine)
  • Muscle protein synthesis and energy production
• Brain requires specific amino acid transporters to cross blood-brain barrier
  • Essential for neurotransmitter synthesis (serotonin from tryptophan)
  • Supports protein synthesis and other neurological functions
• Other tissues utilize amino acids for various processes
  • Immune cells for antibody production
  • Skin for collagen synthesis
  • Endocrine glands for hormone production