24.4 Protein Metabolism

Protein digestion is a complex process that starts in the stomach and finishes in the small intestine. Enzymes break down proteins into amino acids, which are then absorbed and used for various functions in the body.

The urea cycle plays a crucial role in protein metabolism by converting toxic ammonia into urea for safe excretion. This process, along with the body's ability to use proteins as an alternative energy source, highlights the versatility of protein metabolism.

Protein Digestion and Metabolism

Process of protein digestion

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• Protein digestion begins in the stomach where pepsin, an enzyme activated by stomach acid (HCl), starts breaking down proteins into smaller polypeptides
• Majority of protein digestion occurs in the small intestine
  • Pancreatic enzymes (trypsin, chymotrypsin, and carboxypeptidase) secreted into the duodenum further break down polypeptides into smaller peptides and amino acids
  • Brush border enzymes (aminopeptidases and dipeptidases) on the surface of intestinal cells complete the breakdown of peptides into individual amino acids
• Amino acids are absorbed by intestinal cells through active transport and facilitated diffusion and then transported to the liver via the hepatic portal vein
• In the liver, amino acids can be used for protein synthesis (albumin), converted to glucose via gluconeogenesis or ketone bodies via ketogenesis, or broken down for energy through deamination and the citric acid cycle

Role of urea cycle

• Amino acid breakdown produces ammonia (NH3), which is toxic to the body in high concentrations
• The urea cycle, occurring primarily in the liver, converts ammonia to urea (NH2CONH2), a less toxic compound that can be safely excreted by the kidneys
• Steps of the urea cycle:
  1. Ammonia combines with CO2 and ATP to form carbamoyl phosphate catalyzed by carbamoyl phosphate synthetase I
  2. Carbamoyl phosphate combines with ornithine to form citrulline catalyzed by ornithine transcarbamoylase
  3. Citrulline combines with aspartate to form argininosuccinate catalyzed by argininosuccinate synthetase
  4. Argininosuccinate is split into fumarate and arginine by argininosuccinate lyase
  5. Arginine is hydrolyzed to form urea and regenerate ornithine catalyzed by arginase
• Urea is transported from the liver to the kidneys via the bloodstream, where it is filtered and excreted in urine, removing excess nitrogen from the body

Glucogenic vs ketogenic amino acids

• Glucogenic amino acids (alanine, glycine, serine) can be converted to glucose or glycogen through the process of gluconeogenesis in the liver and kidneys
  • Glucogenic amino acids help maintain blood glucose levels during fasting (starvation) or prolonged exercise (marathon running)
• Ketogenic amino acids (leucine, lysine) can be converted to ketone bodies (acetoacetate and β-hydroxybutyrate) in the liver but cannot be converted to glucose
  • Ketogenic amino acids provide an alternative energy source for the brain and heart during prolonged fasting or low-carbohydrate diets (ketogenic diet)
• Some amino acids (phenylalanine, tyrosine, tryptophan) are both glucogenic and ketogenic as their carbon skeletons can be used for either glucose or ketone body synthesis

Proteins as alternative energy

• When carbohydrate intake is low (fasting, low-carb diet) or during prolonged exercise, the body can break down proteins in muscle for energy
• Amino acids undergo deamination, removing the amino group (–NH2) which is converted to urea, and the remaining carbon skeleton is converted into glucose (glucogenic amino acids) or ketone bodies (ketogenic amino acids)
  • Glucose produced from amino acids through gluconeogenesis helps maintain blood glucose levels to fuel the brain and red blood cells
  • Ketone bodies produced from amino acids provide an alternative energy source for the brain and heart during glucose shortage
• Excessive protein breakdown for energy can lead to muscle wasting (cachexia) and impaired immune function (decreased antibody production)
• The body preferentially uses carbohydrates and fats for energy, reserving protein breakdown as a last resort to spare lean body mass

Protein Metabolism and Homeostasis

• Protein synthesis is the process by which cells build new proteins, essential for growth, repair, and maintenance of body tissues
• Essential amino acids are those that cannot be synthesized by the body and must be obtained through diet
• Transamination is a process where the amino group from one amino acid is transferred to another molecule, often in the conversion of one amino acid to another
• Nitrogen balance refers to the state where nitrogen intake equals nitrogen excretion, indicating stable protein metabolism
• Protein turnover is the continuous process of protein synthesis and breakdown in the body, maintaining cellular function and adapting to changing physiological needs