Why is ammonia a tonic and a toxic?

Ammonia is toxic for various reasons:
1) In the ammonium ion form (NH4+), it disrupts Oxidative Phosphorylation by passing through the mitochondrial membrane and messing up the H+ balance.

2) If there is local production of Ammonia as NH3, with a PKa of around 9.3, it will disrupt the H+ balance of the body and hence physiological PH as well

3) It partakes in a redox reaction, hence it disrupts certain redox co-enzyme balances (i.e. NADH/NAD+ and NADPH/NADP+)

 

-Tosin A.O

 

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Ammonia is NEUROTOXIC; it inhibits the formation of neurotransmitters and inhibits the TCA cycle.


While those three reasons listed may play a role, MEDICALLY speaking, the mechanism of ammonium neurotoxicity is unknown. Ammonia is extremely toxic to the brain, which is why our livers possess such a great potential for eliminating ammonia as urea. The current accepted hypothesis as to the effect of elevated blood ammonia is centered on glutamate/glutamine/alpha-ketoglutarate metabolism and the net result of inhibiting the synthesis of valuable neurotransmitters.


Increased ammonia results in alpha-ketoglutarate being converted to glutamate and in turn glutamine. The net result of this is twofold. First, there is decreased TCA cycle activity, as alpha-ketoglutarate is part of the TCA cycle, which means less ATP for the brain. Second, and perhaps more importantly, there are decreased levels of GABA and glutamate in the brain. GABA is a major inhibitory neurotransmitter, whereas glutamate is a major excitatory neurotransmitter. Both have many functions.

 

-A.D.