Glutamine Synthesis
- For nitrogen transport (in the periphery), glutamine synthetase is necessary for the creation of glutamine.
- For nitrogen liberation (in the liver), glutaminase is necessary (specifically for amide nitrogen (not amino-nitrogen) release.
Glutamine synthesis in the brain:
- Glutamate is an excitatory neurotransmitter found in high levels in the brain.
- In too high of levels, however, it can be toxic.
- Ammonium combines with glutamate to produce glutamine.
- Glutamine synthetase catalyzes this reaction with the addition of ATP and that ADP is released along with a phosphate ion.
- Typically this management involves astrocyte to neuron recycling (remaining within the brain).
- Astrocyte/Neuron Recycling
- Glutamate is taken up by astrocytes, converted to glutamine by glutamine synthetase, released, then, taken up by neurons and converted glutamate, and used once again for neurotransmission.
Nitrogen Transport (Urea Cycle)
Nitrogen Transport (Glutamine Synthesis, Glucose/Alanine Cycle)
- In Sum: The body transports and delivers nitrogenous waste (ie, ammonia) to the urea cycle in the liver:
- Glutamine synthesis
- Glucose alanine cycle
Glutamine synthesis:
- Key Organs
- Brain, where we'll show the glutamine synthesis reaction.
- Liver
- Kidneys
- Glutamine structure:
- For nitrogen transport (in the periphery), glutamine synthetase is necessary for the creation of glutamine.
- For nitrogen liberation (in the liver), glutaminase is necessary (specifically for amide nitrogen (not amino-nitrogen) release.
Glutamine synthesis and the brain:
- Glutamate is an excitatory neurotransmitter found in high levels in the brain.
- In too high of levels, however, it can be toxic.
- Ammonium combines with glutamate to produce glutamine.
- Glutamine synthetase catalyzes this reaction with the addition of ATP and that ADP is released along with a phosphate ion.
- Typically, this management involves astrocyte to neuron recycling (remaining within the brain).
- Astrocyte/Neuron Recycling
- Glutamate is taken up by astrocytes, converted to glutamine by glutamine synthetase, released, then, taken up by neurons and converted glutamate, and used once again for neurotransmission.
- Or, it can involve peripheral deamination.
Peripheral deanimation
- In the liver:
- The urea cycle involves both mitochondrial and cytosolic compartments of hepatocytes.
- Glutamine is safely transported to the liver via systemic circulation where glutaminase hydrolyzes the its conversion to glutamate and the liberation of ammonium.
- Ammonium enters the urea cycle.
The Glucose/Alanine Cycle.
- For nitrogen transport (in the periphery), alanine carries nitrogen and is formed as follows: in muscle, glucose converts to pyruvate, which converts to alanine – it carries nitrogen in systemic circulation to the liver.
- For nitrogen liberation (in the liver), glutamate dehydrogenase (GDH) acts via oxidative deamination to liberate nitrogen.
- Alanine is formed in the muscle.
- Glycogen is the main storage form of glucose.
- Via glycogenolysis, glycogen converts to glucose.
- Via glycolysis, glucose converts to pyruvate.
- Via transamination with ALT as the transaminase, pyruvate receives an amino group from glutamate and becomes alanine.
- The deaminated glutamate, then, becomes alpha-ketoglutarate.
- Next alanine leaves muscle to enter systemic circulation and is picked up by the liver.
- In the liver, alanine undergoes the standard two-step reaction:
- Transamination via ALT
- Oxidative Deamination via GDH.
- Thus, alanine gives up its amino group to alpha-ketoglutarate to become pyruvate.
- Alpha-ketoglutarate becomes glutamate.
- Glutamate then deaminates to become alpha-ketoglutarate and its ammonium enters the urea cycle.
- Tthe urea cycle produces urea that exits the body via the kidneys as urine.
- Finally, to make the glucose/alanine cycle a true "cycle", the pyruvate formed in the hepatic transamination converts to glucose via gluconeogenesis, which again is NOT simply the opposite of glycolysis.
- Glucose, then, enters systemic circulation and can be picked up by muscle and converted to alanine via the aforementioned pathway.
- Lastly, consider that branched chain amino acids are particularly interesting because they skip first pass hepatic metabolism – meaning they retain their nitrogen.
- Thus, they are a good source of nitrogen to create alanine and can fuel the glucose/alanine cycle when necessary.