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If nitrogen is so important (it's a constituent of both proteins and nucleic acids), why are animals still throwing them out, and needing to eat it again? Is it true that in almost a billion years of evolution, life still haven't found a way to recycle nitrogen inside the cells or inside the body of multi-cellular organisms? Why does this seem so hard to achieve? Or are there animals that don't need to excrete nitrogen compounds (like ammonia, urea and uric acid), and instead reuse them?

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    $\begingroup$ Ammonia, urea, and uric acid are toxic to the body; why would we want to keep them around? Asking why didn't "x" evolve to happen when what actually has happened is working fairly to extremely well is fairly pointless. $\endgroup$ – anongoodnurse Apr 22 '17 at 1:34
  • $\begingroup$ Also the necessary nitrogen-containing compounds seem to be in more than adequate supply in the diet, so that eating enough calories, proteins, &c provides more than enough nitrogen. What to do with the excess, except excrete it? $\endgroup$ – jamesqf Apr 22 '17 at 5:24
  • $\begingroup$ @anongoodnurse yes they are toxic, but they are created as a by-product. Why not recycle them back into protein and nucleic acids? Then there would be no toxic residuals asking to be excreted. $\endgroup$ – Rodrigo Apr 22 '17 at 5:41
  • $\begingroup$ @jamesqf we store fat and glycogen for energy, but we must eat nitrogen to replace what was excreted. I guess we could pass more time without eating if we were able to recycle nitrogen. This could be an advantage in lots of animal groups, but as far as I know, all animal groups have nitrogen excretion mechanisms. This makes me think nitrogen recycling is somehow very hard for animals to do. The question is: why? $\endgroup$ – Rodrigo Apr 22 '17 at 5:45
  • $\begingroup$ @tomd - Yes, and in nature (before all this population) we used to return that fixed nitrogen to plants which could use them (whereas we can't). Benefits all around. I have two dogs who have not yet learned to use the toilet. You should see my back yard... $\endgroup$ – anongoodnurse Apr 22 '17 at 13:21
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The premise of the question is incorrect. Mammalian organisms do recycle nitrogen. They only excrete excess nitrogen.

Ammonia from deamination of amino acids can be incorporated into glutamate and glutamine:

Incorporation of ammonia into glu and gln

Transamination can then transfer the amino group from glutamate, for example, to other ketoacids for the synthesis of other amino acids.

Transamination

The capacity for recycling nitrogen is presumably determined by requirement. If there is excess to requirement, then there is no evolutionary advantage in retaining the excess and instead a mechanism has evolved to neutralize it and then excrete it.

Addendum: Recycling, yes, but why not also storage?

Although nitrogen from the degradation of amino acids is recycled, the excess is excreted, rather than stored in some form. Why has no storage form (analogous to glycogen or triglyceride) evolved? I will consider this from two inter-related viewpoints.

  1. Yes, nitrogen is important for the proteins required for growth and maintenance of organisms, but the effects of depravation are only seen in the long-term. Carbon is of more immediate importance, i.e. the supply of carbohydrates to provide energy. Indeed, in extreme starvation of mammals metabolism treats muscle protein as expendable, breaking it down for the carbon skeleton of the amino acids. Thus, the selective advantage the evolution of a nitrogen storage system might give to an organism is not so clear.

  2. If there were a nitrogen storage system one needs to consider what form it might take. Obviously not as ammonia, because of its toxicity, but it could be condensed into a neutral form. However a small metabolite, such as glutamate (above), would disrupt the metabolic balance, and a dedicated small molecule such as urea would be excluded because of the effect on osmosis and general water balance. So we are thinking of a macromolecule — a conventional protein like ovalbumin (which may, in fact, be a storage protein), or some special ‘new’ branched protein. The trouble with this method of storing nitrogen is that involves tying up large amounts of carbon — a price, as I argued in 1, that the organism cannot afford to pay.

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  • $\begingroup$ I wonder who downvoted that and why? $\endgroup$ – Rodrigo Apr 24 '17 at 18:30
  • $\begingroup$ @Rodrigo — Don't worry. I don't any more. I actually plan to add some ideas on why the excess nitrogen is excreted rather than stored, which I hope will improve the answer further. $\endgroup$ – David Apr 24 '17 at 18:39
  • $\begingroup$ Well, it will be great if you do that, because it's really interesting. $\endgroup$ – Rodrigo Apr 24 '17 at 22:16
  • $\begingroup$ You might want to add that this process does not offer a way of long-term storage of nitrogen and is only for immediate usage of released ammonia due to side effects of its products and requirement of substrates in other metabolic activities. See my answer. $\endgroup$ – another 'Homo sapien' Apr 25 '17 at 7:23
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    $\begingroup$ @another'Homosapien' — Not that I can think of at the moment. Busy week ahead and am away at the weekend, so low profile until next week. $\endgroup$ – David Apr 25 '17 at 21:02
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Short answer: This is because the most common form of nitrogen found in multicellular organisms (not incorporated into any other compound) i.e. ammonia is too toxic to be stored or recycled.

Background: Ammonia, the product of deamination of amino acids, is basic in nature ($NH_3~+~H_2O \rightarrow NH_4OH \rightleftharpoons NH_4^+ + OH^-$) and thus disturbs intracellular pH (Ohmori et al, 1986). Though the mechanisms through which ammonia exerts its toxic effects are not known, hyperammonemia is known to alter several amino acid pathways and neurotransmitter systems, cerebral energy metabolism, nitric oxide synthesis, oxidative stress and signal transduction pathways, leading to irreversible damage to the developing central nervous system: cortical atrophy, ventricular enlargement and demyelination; causing cognitive impairment, seizures and cerebral palsy (Braissant et al, 2013).

Talking about how it is produced (just for information, skip this part if you are aware of urea cycle): Amino acids are deaminated for storage since the carbon skeleton of these amino acids can be easily converted to glucose or fatty acids for storage. This reaction yields ammonia which, in liver, is converted to urea (via urea cycle) which is not only less toxic, but also requires lesser water for excretion. See this page for more information and the diagram below.

urea cycle

Talking about why it is not recycled, there has always been a constant supply of amino acids to organisms (through nitrogen fixation or food). Indeed, amino acids are deaminated for storage i.e. we already have more than enough of it. Also, storing urea is also not easy since it is toxic too (it is just less toxic than ammonia). And since these products are so much harmful, it seems difficult for an organism to evolve itself so that it can store toxins rather than just throwing it away so that it can later be ingested in a useful form (amino acids from plants or herbivores). Finally, evolution works as decent with modification, meaning if something is a better alternative of current situation, it is not necessary that organisms will evolve towards that (unless there is strong selection pressure for it). In short, evolving to recycle nitrogen is (most likely) just not worth it.

P.S. you might be interested in this question to know more about evolution. Another answer here talks about storing excess nitrogen by adding ammonia into amino acids, yielding glutamate and glutamine. However, this process can be used only to a limited extent due to limited amount of substrate ($\alpha$-keto glutaric acid and glutamate) in the body. Also, excess glutamine in the body can have many major and minor side effects like skin rash, vomiting, etc. (see here for full list). Also, excess glutamate has much more pronounced effects. Since glutamate is a neurotransmitter, its excess causes cellular damage. This is what makes it an excitotoxin (see this for more details). Apart from this, the substrate ($\alpha$-keto glutaric acid) is an intermediate of Krebs cycle and is important in many other cellular activities (see here for details). So, its deficiency (caused due to conversion into glutamate) can easily affect many crucial metabolic activities. Thus, though this process seems an effective way of recycling nitrogen, it has many side-effects and is not much reliable i.e. can only be seen as an immediate solution. This is why when glutamate and glutamine build up in body, they are converted back to $\alpha$-keto glutaric acid and glutamate and the ammonia released via urea cycle.

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  • $\begingroup$ Thank you! I know how evolution works, just thought that, in the huge variability of animal kingdom, there might be some animal able to recycle nitrogen. I disagree that it seems difficult for an organism to evolve itself so that it can store toxins. What about all the venom stored in snakes, wasps, scorpions, spiders, rays...? $\endgroup$ – Rodrigo Apr 22 '17 at 15:23
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    $\begingroup$ @rodrigo venoms are specific to some special proteins (see this), and their effect can thus be prevented by storing them in structures lacking those proteins. Since ammonia disrupts as basic cellular properties as pH, it doesn't seem easy to store it inside a cell/tissue/organ. Yet, there might be organisms who can do so, about whom we don't know yet... $\endgroup$ – another 'Homo sapien' Apr 22 '17 at 17:45
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    $\begingroup$ @Rodrigo: But for animals, the problem is not storing nitrogen, but getting rid of the excess. It's rather like asking why we haven't evolved to store carbon dioxide :-) $\endgroup$ – jamesqf Apr 22 '17 at 18:32
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    $\begingroup$ @another'Homosapien' Right. But we can convert ammonia into urea and store urea (or uric acid, for the animals who use that). Maybe we could convert urea (or uric acid) back into a form of nitrogen that we could use to build more proteins, instead of throwing it out. But it seems there's really an excess of nitrogen in animal diets. $\endgroup$ – Rodrigo Apr 22 '17 at 21:07
  • $\begingroup$ @Rodrigo, if you want to go in that direction, you might ask why we don't just store it in the form of protein (the same way we store fat). I guess you could argue that muscles are in fact big stores of protein :) $\endgroup$ – Victor Chubukov Apr 24 '17 at 21:36

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