Chapter 35: Protein Digestion and Amino Acid Absorption

Protein digestion initiates in the stomach, where hydrochloric acid unfolds protein structures and pepsin catalyzes the initial cleavage of peptide bonds, generating smaller polypeptide fragments. The small intestine then becomes the primary site of proteolysis, as pancreatic zymogens including trypsinogen, chymotrypsinogen, proelastase, and procarboxypeptidases undergo activation through the action of enteropeptidase and autocatalytic trypsin, systematically reducing proteins into oligopeptides and individual amino acids. The intestinal brush border and enterocyte cytoplasm house additional peptidases that complete the digestive process, ensuring maximal amino acid liberation. Absorption across the intestinal epithelium occurs through multiple transporter systems: sodium-dependent cotransporters actively pump amino acids against their concentration gradient, while facilitated diffusion pathways accommodate additional amino acid uptake, with each system displaying selectivity for neutral, basic, acidic, or imino amino acids. Transport defects generate clinically significant syndromes—cystinuria impairs cystine and basic amino acid reabsorption, predisposing to urinary stone formation, while Hartnup disease disrupts neutral amino acid absorption, precipitating pellagra-like neurological symptoms. Cystic fibrosis demonstrates how compromised pancreatic enzyme secretion severely limits proteolysis and malabsorption. Beyond digestion, the chapter addresses protein turnover through two degradation systems: lysosomal cathepsins break down internalized proteins, and the ubiquitin-proteasome complex selectively targets damaged or transient proteins for adenosine triphosphate-dependent destruction. Recycled amino acids refill the intracellular amino acid pool, supporting new protein synthesis, gluconeogenesis, or oxidative metabolism. Alpha-1-antitrypsin deficiency exemplifies how inadequate protease inhibition allows neutrophil elastase to damage lung tissue, causing emphysema. The gamma-glutamyl cycle functions in glutathione synthesis, providing essential antioxidant defense. Collectively, these processes maintain nitrogen equilibrium, facilitate growth and repair, and establish metabolic homeostasis, while their disruption produces protein malnutrition, genetic disorders, and systemic disease.