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Lecture 42 Amino acid catabolism and the urea cycle
When is amino acid catabolism active?
Fed and fasted states
What does amino acid catabolism do in the absoptive phase?
Excess dietary amino acids are catabolized for amino acid homeostasis and energy production in the liver
What is amino acid catabolism do in the posabsorptive phase?
Amino acids are catabolized and feed into gluconeogenesis and ketogenesis
Where does amino acid catabolism take place?
in the liver (except for BCAA and glutamine)
What is the role of pyridoxal phosphate (vitamin B6) in amino acid catabolism?
Present at the catalytic site of all aminotransferases
temporarily holds the amino group as it is transfered from amino acid to alpha ketoglutarate
What amino acid is the major precursor to pyruvate?
Which enzyme catalyzes the reaction?
Alanine aminotransferase (ALT)
Which amino acid uses glutamate and oxaloacetate (OAA) as precursors?
What enzyme catalyzes the reaction?
Aspartate amino transferase (ALT)
Where in the body are aminotransferases found?
liver, kidney, intestine, muscle
Elevated levels of which aminotransferases indicates cell damage?
AST and ALT
Which aminotransferase is elevated in myocardial infarction?
What is the primary source of ammonia?
glutamate dehydrogenase (oxidative deamination)
What is the secondary sources (4) of ammonia?
Degredation of purine and pyrimidine nucleotides
Glutamine metabolised by the GI tract
Glutamine metabolised by kidney
Urea degraded by bacteria
What is a second means (besides the creation of urea) to decrease blood ammonia?
Hepatic glutamine synthesis
What four ways is the urea cycle regulated?
Compartmentalization (CPSI is in mitochondria, CPSII is in cytosol)
Substrate availability (increase in ammonia-->increase in CPSI)
Allosteric effectors (increase in protons (acidosis)-->decrease CPSI, increase in N-acetylglutamate-->activates CPSI)
Gene expression (quantity of dietary protein, glucagon, insuslin, cortisol)
How does hepatic cirrhosis lead to hyperammonemia?
hepatocytes are replaced with fibroblasts which lack urea cycle and glutamine synthesis resulting in higher ammonia levels
How does portal hypertension lead to hyperammonemia?
prevents portal blood from easily entering the liver which leads to the formation of collateral circulation shunting of ammonia rich portal blood away from the liver and into systemic circulation
What symptoms does hyperammonemia result in?
tremors, slurring of speech, blurry vision, cerebral edema, coma
Does ammonia cross the blood brain barrier BBB?
Yes! it readily crosses the blood brain barrier
What are the dangers of ammonia in the brain (increased synthesis of gutamate and glutamine)?
Glutamate is a neurotransmitter and can activate N-methyl-D-aspartate (NMDA) receptors which may trigger the events of ammonia toxicity
Increased glutamine is trapped in the brain leading to cerebral edema