4
403710
What exactly is the mechanism by which arginine supplementation can help with urea cycle disorders? And does it help with ALL causes of Urea cycle disorders d/t enzymatic deficiencies? (I believe there are 5 or so).
Arginine is normally a nonessential amino acid as the body normally produces it via the Urea cycle. When we knock out the urea cycle arginine becomes essential and must be obtained through supplementation or food sources so we can continue to have adequate amounts for functions such as nitric oxide production.
You still need to limit protein intake with urea cycle defects as the arginine supplementation is not going to allow for proper urea cycle function.
Hopefully that makes sense.
Sent from my iPhone using SDN mobile
You still need to limit protein intake with urea cycle defects as the arginine supplementation is not going to allow for proper urea cycle function.
Hopefully that makes sense.
Sent from my iPhone using SDN mobile
Last edited:
4
403710
That does, I appreciate the added correlate of this being the mechanism by which arginine becomes essential. Is it not involved in the pathway of allowing for more urea production that would allow for increased NH3 excretion?
My question is basically- What is the mechanism by which we treat the hyperammonemia associated with urea cycle disorders?
My question is basically- What is the mechanism by which we treat the hyperammonemia associated with urea cycle disorders?
So as far as I understand, there are no treatments to increase urea production. You treat it by minimizing ammonium production (limiting protein intake) and can also use benzoate, phenylacete, or phenylbuytrate which help clear glutamine really, however they do not increase urea production.
Sent from my iPhone using SDN mobile
4
403710
Would you elaborate on that a little please- how would using Benzoate, phenylacetate, phenylbutyrate to increase Glutamine/Glycine clearance counteract the hyerammonemia? There's something I'm not getting.
So glutamate in its original form cannot be excreted from the kidneys. Normally the nitrogen from glutamate is excreted via urea cycle. So without the urea cycle the nitrogen accumulates and is toxic. Essentially, Benzoate, phenlybutrate, and phenylacetate react with nitrogen and create products that can be excreted by the kidneys, therefor eliminating the excess nitrogenous waste.
Sent from my iPhone using SDN mobile
4
403710
My question is how exactly does the glutamate become the glutamine, that is worked on by the benzoate/phenylacetate/phenylbutyrate. I know theres a glutamate-glutamine cycle (astrocytes taking up excess glutamate from synaptic spaces and converting it to glutamine that they then pass back to neurons), but i dont think this is involved in this process, is it?
Again, really appreciate your attention to this.
Again, really appreciate your attention to this.
Glutamate + ammonia ---> glutamine via glutamine synthetase. So it's the same concept as what you mentioned occurs in astrocytes. Glutamine acts as a non toxic carrier but it has to get rid of the toxic ammonia eventually, which is where benzoate and the others come in and allow for renal excretion. Alanine also acts as a nontoxic carrier of ammonia. (FA 2017 pg 78).
Hopefully that is what you're wondering about. If not, maybe someone else can chime in.
Sent from my iPhone using SDN mobile
- Joined
- Aug 5, 2013
- Messages
- 674
- Reaction score
- 466
From what ive learned, since glutamine basically has 2 NH3 groups (ie the things you want to get rid of in hyperammonemia), the phenylacetate just forms a complex with glutamine, forming phenylacetylglutamine which is excreted in the urine. (basically think of it as a chelating agent, even though its not sequestering metals)
