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Chapter 29: Nitrogen: Nitrogen Homeostasis and Disposal via Urea

The waste nitrogen from skeletal amino acid catabolism is diverted to the liver for incorporation into urea in which of the following compounds?

A. alanine

B. asparagine

C. aspartate

D. glutamate

E. phenylalanine

Answer A: Alanine transaminase has an important function in the delivery of skeletal muscle carbon and nitrogen (in the form of alanine) to the liver. In skeletal muscle, pyruvate is transaminated to alanine, thus affording an additional route of nitrogen transport from muscle to liver. In the liver, alanine transaminase transfers the ammonia to α-ketoglutarate and regenerates pyruvate. The pyruvate can then be diverted into gluconeogenesis. This process is referred to as the glucose-alanine cycle.

When the body becomes acidotic the liver and the kidneys play central roles in reactions designed to reduce the pH of the blood. Which of the following constitutes the primary critical hepatic reaction occurring during periods of acidosis?

A. ammonia incorporation into glutamate forming glutamine

B. ammonia incorporation into α-ketoglutarate forming glutamate

C. glutamine conversion to glutamate releasing ammonia

D. glutamine conversion to α-ketoglutarate releasing ammonia

E. increased production of urea to dispose of ammonia

Answer A: Major reactions that involve the regulation of plasma pH as well as the level of circulating ammonia involve the hepatic and renal enzymes glutamate dehydrogenase (GDH), glutamine synthase (GS), and glutaminase. The liver compartmentalizes GS and glutaminase in order to control the flow of ammonia into glutamine or urea. Under acidotic conditions the liver diverts ammonia to glutamine via the GS reaction. The glutamine then enters the circulation. In fact, glutamine is the major amino acid of the circulation and its role is to ferry ammonia to and from various tissues. In the kidneys, glutamine is hydrolyzed by glutaminase (yielding glutamate) releasing the ammonia to the urine. There the ammonia ionizes to ammonium ion, NH4+, which reduces the circulating concentration of hydrogen ion resulting in an increase in the pH. Additionally, the glutamate can be converted to α-ketoglutarate yielding another mole of ammonia, which is ionized by hydrogen ions further increasing the pH.

Glutamate dehydrogenase is an extremely important enzyme involved in nitrogen homeostasis. This enzyme catalyzes a reversible reaction that either incorporates or liberates ammonium ion. When catalyzing the reaction in the direction of ammonium ion liberation, the enzyme is allosterically activated by which of ...

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