Metabolism VIII Flashcards
What happens to the excess nitrogen (NH4+) formed in the urea cycle?
It is converted to urea and excreted by the kidneys (p.106)
What is the rate limiting enzyme in the urea cycle?
Carbamoyl phosphate synthetase I (p.106)
Where does the rate limiting step in the urea cycle occur?
In the mitochondria (p.106)
Describe the pathway of the urea cycle.
Carbamoyl phosphate (produced from Co2 + NH4+ by carbamoyl phosphate synthase I in the mitochondria) is converted to citrulline in the cytosol. Citrulline + aspartate –> Arhinocuccinate –> Fumarate (leaves the cycle) + Arginine. Arginine –> Urea (excreted) + Ornithine. Ornithine then joins with carbamoyl phosphate from the mitochondria to form citrulline and to begin the cycle again (p.106)
What is the role of aspartate in the urea cycle?
To donate a NH4+ (p.106)
Which two products leave the urea cycle?
Urea and Fumarate (p.106)
What is the alanine cycle?
Functions to produce alanine in muscle cells which can be transported to the liver. In the liver, alanine is used to produce urea and also produces pyruvate which can be converted to glucose (via anaerobic metabolism in the cori cycle) which can then be transported back to the muscle for use (p.106)
Which two amino acids are responsible for ammonium transport?
Alanine and glutamate (p.106)
What can cause hyperammonemia?
Hereditary deficiency (e.g. urea cycle enzyme deficiencies) or aquired through liver disease (p.107)
What are the physiologic consequences of hyperammonemia?
Excess NH4+ which depletes a-ketoglutarate and inhibits the TCA cycle (p.107)
How is hyperammonemia treated?
By limiting protein in the diet (p.107)
What are the symptoms of ammonia intoxication?
Tremor (asterixis), slurring of speech, somnolence, vomiting, cerebral edema, blurring of vision (p.107)
What can be given to a patient to lower ammonia levels?
Benzoate or phenylburtyate bind amino acids and lead to excretion; lactulose can acidify the GI tract and trap NH4+ for excretion (p.107)
Describe the pathology associated with an ornithine transcarbamoylase deficiency.
Deficient enzyme that interferes with the body’s ability to eliminate ammonia. Excess carbamoyl phosphate is converted to orotic acid as part of the pyrimidine synthesis pathway (p.107)
Describe the pattern of inheritance associated with an ornithine transcarbamoylase deficiency.
X linked recessive (it is the only urea cycle enzyme deficiency that is not autosomal recessive) and is the most common urea cycle disorder (p.107)
