Protein Turnover and Krebs Cycle

Protein Turnover

• Protein turnover is the continual renewal or replacement of protein, defined by the balance between protein synthesis and protein degradation.

Dietary Protein Digestion

• Amino acids are used for protein synthesis, synthesis of other amino acids, and synthesis of other nitrogen-containing compounds.
• Excess amino acids are degraded to produce ATP.

Amino Acid Degradation

• Removal of nitrogen (α-amino group) by deamination/transamination.
• Carbon skeleton conversion into Krebs cycle intermediates.

Fate of the α-Amino Group

• Transamination: transfer of an amino group from one amino acid to another α-keto acid by transaminase (aminotransferase).
• Oxidative deamination: amino group is removed from an amino acid, resulting in the formation of a corresponding keto acid and ammonia.

Urea Cycle

• Consists of five sequential enzymatic reactions.
• First two reactions take place at the mitochondria, and the remaining three reactions at the cytosol.
• The urea cycle is a pathway for the removal of excess nitrogen from the body.

Mitochondrial Stage

• Carbamoyl phosphate is formed from ammonia and bicarbonate by carbamoyl phosphate synthetase.
• Citrulline is formed from the condensation of carbamoyl phosphate and ornithine by transcarbamoylase.

Cytosolic Stage

• Argininosuccinate synthetase condenses citrulline and aspartate to form argininosuccinate.
• Argininosuccinate is broken down into arginine and fumarate by argininosuccinate lyase.
• Arginine is broken down into urea and ornithine by arginase.
• Ornithine translocase transports ornithine into the mitochondria.

Urea Cycle Mnemonics

• ORNITHINE (O)
• COLORED (C)
• CATS (C)
• ALWAYS (A)
• ASK (A)
• FOR (F)
• AWESOME (A)
• UMBRELLAS (U)

Urea Cycle Disorder

• Defect in any of the 5 enzymes in the urea cycle may lead to NH3 accumulation.
• Ammonia is a potent neurotoxin; normal level is below 50 μmol/L.
• Hyperammonemia is a metabolic condition characterized by raised levels of NH3.

Fate of Amino Acid Carbon Skeleton

• Converted into an intermediate of the citric acid cycle once the amino group is removed.
• Glucogenic amino acids are converted to glucose via gluconeogenesis.
• Ketogenic amino acids are converted to acetoacetyl-CoA or acetyl-CoA and can be used for the synthesis of ketone bodies.

Ketogenesis

• A metabolic pathway that produces ketone bodies, which provide an alternative form of energy for the body.
• Body is constantly producing small amounts of ketone bodies that can make 22 ATP each in normal circumstances.
• Ketosis is a state in which ketone body production is increased when there are decreased carbohydrates or increased fatty acids.

Ketone Bodies

• β-hydroxybutyrate
• Acetoacetate
• Acetone
• Acetoacetate and β-hydroxybutyrate are the primary ketone bodies in circulation, which can be used as fuel in most tissues, except the liver.

Amino Acid Classification

• Based on their catabolism:
  • Glucogenic
  • Ketogenic
  • Both glucogenic and ketogenic

This quiz covers the concepts of protein turnover, including protein synthesis and degradation, and the Krebs cycle. Understand the process of protein renewal and replacement, as well as the key steps in the Krebs cycle.