Oligopeptide Digestion and Kwashiorkor Syndrome

Digestive Enzymes and Protein Stability

• Cytosolic proteins show varied reactivity based on amino acid terminal structure.
• Short-lived proteins, such as regulatory and misfolded proteins, have half-lives of minutes to hours.
• Long-lived proteins (e.g., most cellular proteins) have half-lives of days to weeks.
• Structural proteins, like collagen, are metabolically stable with half-lives of months to years.
• Muscle protein breakdown involves the release of 3-methylhistidine, which is excreted in urine.

Protein Digestion and Absorption

• Dietary proteins are too large for intestinal absorption; they must be hydrolyzed into amino acids.
• Proteolytic enzymes from the stomach, pancreas, and small intestines facilitate this process.
• Gastric juice (including hydrochloric acid and pepsin) denatures proteins and initiates digestion.
• Pepsin, an acid-stable endopeptidase, breaks down proteins into large polypeptides and free amino acids.

Enzymatic Digestion in the Small Intestine

• Aminopeptidases and dipeptidases at the intestinal lumen cleave amino acids from oligopeptides.
• Dipeptides and tripeptides are absorbed and further digested to free amino acids in intestinal epithelial cells.
• Free amino acids and dipeptides are transported to the liver via the portal system.

Amino Acid Transport Mechanisms

• Active transport systems, driven by ATP hydrolysis, pump amino acids into cells against a concentration gradient.
• A significant gradient exists for glutamate and glutamine uptake.
• The COAL system facilitates the uptake of cystine and dibasic amino acids (ornithine, arginine, lysine).
• Transport mechanisms include Na+-dependent (luminal) and Na+-independent (contraluminal) pathways.

Nitrogen Disposal and Amino Acid Catabolism

• Nonhepatic diseases lead to increased plasma levels of transaminases, indicative of tissue damage.
• Transamination transfers amino groups to glutamate, the first step in amino acid catabolism.
• Oxidative deamination liberates ammonia as a byproduct, primarily in the liver and kidneys.
• Glutamate dehydrogenase plays a key role in regenerating α-ketoglutarate and catalyzing oxidative deamination.

Role of Coenzymes and Regulators

• Oxidized forms of NAD (NAD+) and NADP (NADP+) serve as coenzymes in deamination reactions.
• The normal NADPH/NADP+ ratio in liver is high, supporting various metabolic pathways.
• Reaction direction relies on concentrations of glutamate, α-ketoglutarate, ammonia, and oxidized/reduced coenzyme ratios.
• Allosteric regulation of glutamate dehydrogenase occurs with ATP, GTP, and NADH acting as inhibitors, while ADP and GDP serve as activators.

Alternative Deamination Mechanisms

• L- and D-amino acid oxidases facilitate oxidative deamination, particularly in kidneys and liver.
• D-amino acid oxidase, a FAD-dependent enzyme, catalyzes the deamination of D-amino acids, creating ketoacids.
• Direct deamination can occur through dehydratases like serine and threonine dehydratases, utilizing pyridoxal phosphate.

Ammonia Transport to the Liver

• Two primary mechanisms transport ammonia to the liver:
  • First Mechanism: Involves glutamine synthetase and glutaminase, prevalent in most tissues.
  • Second Mechanism: Operates primarily in muscles and involves the transamination of pyruvate to alanine.

Explore the digestion of oligopeptides by the enzymes located in the small intestines, including aminopeptidases and dipeptidases. This quiz also covers the consequences of high protein diets and the metabolic pathways of excess amino acids. Test your knowledge on these essential biochemical processes!