It is said that erythrocytes, polymorphonuclear leukocytes and brain cannot produce purines. And the reason given as per this site is:

Human brain tissue has a low level of PRPP glutamyl amidotransferase (reaction Image, Figure 33–2) and hence depends in part on exogenous purines. Erythrocytes and polymorphonuclear leukocytes cannot synthesize 5-phosphoribosylamine (structure III, Figure 33–2) and therefore utilize exogenous purines to form nucleotides.

My question is why do these cells don't produce the required enzymes for the synthesis of purines? What could be the functional significance for such absence?

My attempt : At first I thought that Erythrocytes as such don't have nucleus so they don't need purine synthesis for cell division , but I don't understand why then they need purines from external source( as said in the above site). Also brain cells are neurons and neuroglia, of which former doesn't divide( except in some areas of brain) but they too need purines. The later divide but they don't produce required enzyme. Why?

So my questions are:

  1. Why do cells which don't replicate need purines?( May be for formation of Coenzymes , correct me if Iam wrong)

  2. Why do the cells which divide too don't produce required proteins(enzymes)?

  • $\begingroup$ Should I make it in two parts? $\endgroup$ – JM97 May 17 '17 at 7:59
  • $\begingroup$ I can't answer it, but it seems a reasonable question to me. It has received a close vote as too broad. But perhaps you should remove questions 3 and 4 as understanding why the nucleated cells here differ from other cells in purine metabolism will probably suggest answers to those questions. $\endgroup$ – David May 17 '17 at 13:07
  • $\begingroup$ @David I have edited the question, have a look at it. $\endgroup$ – JM97 May 17 '17 at 13:55
  • $\begingroup$ Question seems valid enough to me. And interesting. $\endgroup$ – David May 17 '17 at 14:48
  • $\begingroup$ I agree. A stellar question. Erythrocytes start with nuclei and jettison them before leaving the marrow so that is not it. There are active synthetic systems making the stuff nearby and so it would be no big deal for these cells to do it too. The synthetic path must be off for a reason. $\endgroup$ – Willk May 18 '17 at 1:50

I am going to throw this idea out there. I was unable to find it stated anywhere so far.

There are several very ancient parasites that make their homes inside erythrocytes and neutrophils. Plasmodium is one, the causative agent of malaria. Trypanosoma is another. These things are ancient degenerate eukaryotes and their lifestyle as intracellular parasites is probably ancient too.

These things cannot make purines either but they need them and they need a lot of them, because they are reproducing fast. If the host cell does not have the machinery to make purines, that machinery cannot be hijacked by the parasite to really crank out the purines. The best they can do is hijack the salvage pathways these cells have.

From https://www.ncbi.nlm.nih.gov/pmc/articles/PMC259377/

The apparent competition between parasites and host cells for available purines suggests that depletion of extracellular purines should be considered as an approach to treating extracellular trypanosome infections.

From https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4405406/

Plasmodium species parasites, like many other protozoan parasites, are purine auxotrophs, unable to perform de novo purine biosynthesis. They rely on the host to provide purines

That does not explain brain cells - unless lack of purine synthesis is a defense of brain cells against Toxoplasma, yet another eukaryotic parasite.

Nothing would please me more than for someone to poke holes in this theory. A prediction from this theory: erythryocytes in all animals should lack purine synthesis - including birds, who suffer from a form of malaria and whose erythrocytes do have nuclei.

  • 1
    $\begingroup$ Quite interesting theory. $\endgroup$ – JM97 May 18 '17 at 2:32
  • $\begingroup$ What about hepatocytes? They too get infected by plasmodium, but are the major sites of purine synthesis. $\endgroup$ – JM97 May 18 '17 at 2:54
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    $\begingroup$ @JM97: I suspect the circulating cells & esp erythrocytes are more dispensible (like pawns in chess) so adaptations there are less detrimental to the organism. Hemoglobinopathies (sickle cell, thalassemia) are thought to have evolved as defenses against plasmodium infection and their actions are also specific to the erythrocyte. $\endgroup$ – Willk May 18 '17 at 12:48
  • $\begingroup$ Then why Polymorphonuclear leucocytes too don't produce purines? $\endgroup$ – JM97 May 18 '17 at 12:54
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    $\begingroup$ @JM97 Same argument as RBC. PMNs are shortest-lived wbc and dispensable: shock troops. They engulf parasites and then die, taking parasite with them. Some parasites (Leishmania, trypanosomes) can survive and reproduce in PMNs. Lack of endogenous purine synthesis machinery makes life harder for these parasites. Be aware: I am making this up as I go. $\endgroup$ – Willk May 18 '17 at 18:13

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