Overview
This lecture covers the key steps of amino acid metabolism, focusing on transamination and deamination reactions, their role in energy production, gluconeogenesis, and clinical significance.
Amino Acid Transamination
- Transamination is the transfer of an amine group from an amino acid (e.g., alanine) to a keto acid (e.g., alpha-ketoglutarate).
- The enzyme alanine aminotransferase (ALT) catalyzes the transfer, using pyridoxal phosphate (from vitamin B6) as a cofactor.
- Alanine and alpha-ketoglutarate are converted to pyruvate and glutamate, respectively, during this process.
- Transamination reactions are reversible and occur with various amino acids (e.g., aspartate with aspartate aminotransferase or AST).
Fate of Transamination Products
- Pyruvate formed in muscle can be converted to lactic acid (Cori cycle) or to acetyl-CoA for entry into the Krebs cycle (ATP production).
- Lactic acid moves to the liver, where it is reconverted to glucose via gluconeogenesis (Cori cycle).
- Glutamate travels to the liver for further metabolism.
Oxidative Deamination and Ammonia Disposal
- In the liver, glutamate undergoes oxidative deamination by glutamate dehydrogenase, producing alpha-ketoglutarate and ammonia (NH3).
- NADP+ is reduced to NADPH during this reaction, important for fatty acid synthesis and free radical reactions.
- The toxic ammonia is converted to ammonium (NH4+), which will enter the urea cycle for detoxification.
Interconnections with Energy and Glucose Production
- Amino acids can feed into Krebs cycle intermediates or be used to generate glucose (gluconeogenesis).
- Many amino acids can be converted into intermediates such as pyruvate, oxaloacetate, succinyl-CoA, and acetyl-CoA.
- These processes allow amino acids to contribute to ATP production or glucose synthesis.
Clinical Relevance
- ALT and AST enzymes are present in muscle, heart, and liver tissues.
- Tissue damage (e.g., from a heart attack or liver disease) releases these enzymes into the blood.
- Elevated ALT/AST levels in blood tests indicate possible liver or cardiac damage.
Key Terms & Definitions
- Transamination — Transfer of an amine group between an amino acid and a keto acid.
- Alanine Aminotransferase (ALT) — Enzyme catalyzing transamination of alanine and alpha-ketoglutarate.
- Aspartate Aminotransferase (AST) — Enzyme catalyzing transamination of aspartate.
- Pyridoxal Phosphate — Vitamin B6-derived cofactor for transaminase enzymes.
- Oxidative Deamination — Removal of an amine group from glutamate, producing ammonia.
- Glutamate Dehydrogenase — Enzyme catalyzing oxidative deamination of glutamate.
- Cori Cycle — Conversion of lactate (from muscle) to glucose (in liver).
- Gluconeogenesis — Formation of glucose from non-carbohydrate sources.
Action Items / Next Steps
- Review the urea cycle to understand ammonia detoxification.
- Study enzyme mechanisms for ALT and AST reactions.
- Prepare for questions on clinical implications of elevated liver/cardiac enzymes.