Small group 1 - problem 3 Flashcards
A 3-month old female infant seemed normal until she developed seizures. The infant became progressively worse, showing reduced muscle tone, retardation of mental and motor development, and poor head control. She had elevated lactate and lactic acidosis; she also had elevated plasma pyruvate. Both lactate and pyruvate were increased 5-7 fold. The plasma alanine concentration was high, and an alanine load failed to induce a normal gluconeogenic response.
Identify the biochemical reaction catalyzed by pyruvate carboxylase and the cellular localization of this enzyme
Pyruvate + CO2 + ATP –> Oxaloacetate + ADP + Pi
The activity of the enzyme pyruvate carboxylase is dependent on activation by __________
Acetyl CoA
Explain the metabolic function of pyruvate carboxylase.
Provide the oxaloacetate needed for the Krebs cycle. The more OAA that is present, the more efficiently the cycle operates. Without OAA, the cycle ceases to function.
What happens when alpha-ketoglutarate or OAA are transaminated to aspartate or glutamate?
The TCA cycle is broken
Which organs is pyruvate carboxylase present in higher amounts in?
Liver and kidney (gluconeogenic organs)
What are large amounts of cytosolic OAA (provided by pyruvate carboxylase) used for?
Synthesis of phosphenolpyruvate
Why would an alanine load fail to induce gluconeogenesis?
Alanine can be taken up by most cells and transaminated to pyruvate, but the pyruvate would not have been able to be made into OAA for gluconeogenesis because of the defective pyruvate carboxylase.
