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5 Exercise amino acid metabolism
Before you attempt this tutorial read about gluconeogenesis (chapter 8) and amino acid metabolism (chapter 15)
Data from: Pyruvate-Carboxylase-Mediated Anaplerosis Promotes Antioxidant Capacity by Sustaining TCA Cycle and Redox Metabolism in Liver, Cell Metabolism 2019
Pyruvate carboxylase catalyses a key anaplerotic reaction of the TCA cycle.
Question 1: What reactions are considered anaplerotic reactions?
- Reactions that remove TCA cycle intermediates
- Reactions of the TCA cycle
- Reactions or pathways that generate TCA cycle intermediates using metabolites outside the TCA cycle.
- Reactions that generate acetyl-CoA
- Reactions or pathways that generate TCA cycle intermediates using metabolites outside the TCA cycle.
In a recent study mice were generated which had a liver-specific knock-out of the pyruvate carboxylase gene (PC)
What metabolic consequences to you expect if pyruvate carboxylase is missing in liver?
Study the following figure and answer the subsequent questions.
The levels of which amino acids are reduced in the liver of the ko mice?
Aspartate and glutamate
The levels of which amino acids are elevated in the liver of the ko mice?
alanine, arginine, citrulline, lysine
In what metabolic pathways do arginine and citrulline play a critical role?
The urea cycle
What does elevation of citrulline and arginine suggest?
The urea cycle is slowed down and arginine cannot unload sufficient urea. This is also supported by elevated levels of ammonia.
Why is alanine elevated in the liver of the ko mice?
Alanine is a major precursor for gluconeogenesis. It is converted via pyruvate and pyruvate carboxylase to oxaloacetate to form glucose.
Why is lysine elevated in the liver of the ko mice?
Consider the metabolic pathway for lysine in this reference:
Breakdown of lysine requires alpha-ketoglutarate at two steps. This TCA cycle member must be depleted in the ko mice.
