Amino acid metabolism II. The urea cycle

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Amino acid metabolism II. The urea cycle

• Figures
• Lehninger-4ed chapter 18
• Stryer-5ed chapter 23

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Overview of amino acid catabolism in mammals
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Excretory forms of nitrogen
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In ureotelic organisms, the NH3 deposited in the
mitochondria of hepatocytes is converted to urea
in the urea cycle. This pathway was discovered by
Hans Krebs (citric acid cycle) and Kurt
Henseleit. Urea production occurs almost
exclusively in the liver and is the fate of most
of NH3 channeled there. Urea ? bloodstream ?
kidneys ? urine
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Possible sources of ammonia ? Amino acid
degradation in every organ, especially in the
liver and muscles ? Ammonia secretion (5-10
of whole N turnover) in kidney tubules from
glutamine (Chinese Restaurant) ? Nucleotide
(pyrimidine) degradation ? Intestinal bacteria
produce it from amino acids and urea Ammonia is
very toxic ? cerebral edema, increased cranial
pressure (depletion of ATP in brain
cells?)
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Links between the urea cycle and citric acid cycle
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The energetic cost of urea synthesis 2NH4
HCO3 3ATP H2O ? urea 2ADP 4Pi AMP
2H ? requires 4 high-energy phosphate groups ?
NADH is produced in the malate dehydrogenase
reaction (urea cycle ? citric acid cycle) ? NADH
2.5 ATP (mitochondrial respiration) ? The
overall energetic cost of urea synthesis is
reduced!
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Regulation of the urea cycle