Protein Turnover and Steady State

Protein Turnover

• Steady state of amino acid pool maintained (input = output).
• Constant degradation and synthesis of proteins regulated by cellular concentration.
• Approximately 300-400g of proteins are hydrolyzed and resynthesized daily.
• Protein turnover varies by lifespan:
  • Short-lived: regulatory/misfolded proteins.
  • Long-lived: most tissue proteins.
  • Structurally stable: collagen.

Nitrogen Balance

• Occurs when nitrogen intake equals nitrogen output.
• Positive Nitrogen Balance: more intake than output, indicating tissue growth.
  • Common during growth, pregnancy, muscular training, and prolonged positive nitrogen balance.
• Negative Nitrogen Balance: output exceeds intake, leading to potential health issues.
  • Consequences include starvation, malnutrition, chronic diseases, and increased catabolism.

Protein Metabolism

• Degradation via two systems:
  • Energy-dependent ubiquitin-proteasome mechanism for endogenous proteins.
  • Non-energy-dependent lysosomes for extracellular proteins.
• Proteins with specific N-terminal residues influence their half-life.
  • Serine at N-terminal: long half-life (>20h).
  • Aspartate at N-terminal: short half-life (3min).
  • PEST-rich sequences result in rapid degradation.

Digestion of Proteins

• Proteins are antigenic and lose this property upon digestion.
• In stomach:
  • Gastric acid denatures proteins.
  • Pepsin becomes active from pepsinogen through HCl, catalyzing protein cleavage.
• In small intestine:
  • Pancreatic proteases cleave polypeptides into smaller units.
  • Enteropeptidase activates trypsin, which catalyzes further proteolytic activity.

Abnormalities in Protein Digestion

• Deficiencies in pancreatic secretion lead to incomplete protein and fat digestion.
• Resulting conditions include steatorrhea (abnormal lipid appearance) and undigested protein in feces.
• Aminopeptidases in the intestine cleave N-terminal residues, producing free amino acids and smaller peptides.

Transamination

• Aminotransferases catalyze transfer of amino groups to carbon skeletons, predominantly in liver, kidney, intestine, and muscle.
• All amino acids except lysine and threonine participate in transamination.
• Lysine and threonine undergo deamination instead.

Aminotransferases

• Each aminotransferase has specific amino group donors.
• Examples:
  • Alanine aminotransferase (ALT) transfers alanine's amino group to α-ketoglutarate, forming pyruvate and glutamate.
  • Aspartate aminotransferase (AST) transfers from glutamate to oxaloacetate, forming aspartate.

Mechanism of Action of Aminotransferases

• Require pyridoxal phosphate as a coenzyme to transfer amino groups.
• Converts amino acid to aldehyde form, enabling subsequent reactions with α-keto acids.

Diagnostic Value of Plasma Aminotransferases

• Elevated aminotransferases indicate cellular damage, particularly in hepatic tissue.
• AST and ALT levels rise in liver diseases and conditions like myocardial infarction.
• Distinguish between hepatic and non-hepatic causes of elevation.

Glutamate Dehydrogenase

• Catalyzes oxidative deamination of glutamate, releasing free ammonia.
• Primarily active in liver and kidney, utilizing NAD or NADP.
• Regulation occurs through substrate concentration and coenzyme ratios.

Transport of Ammonia to Liver

• Two mechanisms for ammonia transport:
  • Glutamine synthetase forms glutamine in most tissues, transported to the liver.
  • Muscle utilizes transamination to form alanine, transported to liver for gluconeogenesis.

Hyperammonemia

• Result of compromised liver function or genetic defects in the urea cycle, leading to dangerous ammonia levels.
• Symptoms include neurotoxicity, tremors, slurred speech, and potential coma or death.
• Treatment involves dietary protein limitation and administration of compounds that facilitate nitrogen excretion (e.g., phenylbutyrate).

Explore the concept of protein turnover and its regulation in this quiz. Learn about the constant processes of protein degradation and synthesis, and understand how these are influenced by protein concentrations within cells. Test your knowledge on the differences between short-lived and long-lived proteins.