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I would like to know when the term Pi (inorganic phosphate) was introduced in the representation of biochemical reactions, how it was originally defined, and the justification given then for using it rather than an individual species of phosphate.

(I would also be interested in the current justification, but that’s probably another question.)

Let me provide some background to my question. Phosphoric acid (H3PO4) has three ionizations, which produce successively the species: dihydrogen phosphate (H2PO4), monohydrogen phosphate (HPO42–) and orthophosphate (PO43–). At pH 7.4, according to the Wikipedia entry on phosphate, the main species are the mono- and di-hydrogen phosphates (61% and 39% respectively). The term Pi must have been introduced in the 1950s at latest (perhaps before the war), at a time when there would have been little knowledge of the nature of the species involved in reactions involving phosphate — certainly not at the active sites of enzymes.

One of the reasons I am curious to know how the term was introduced is the extent to which it persists in 21st century biochemical text books, where it would seem that many authors either do not know or do not care to explain to their readers why they are still using it at a time when much more is known about the reaction mechanisms. Neither of two well-known texts explain the different ionizations of phosphate, and give only parenthetical definitions in terms of a single species — different in each case: Berg et al. referred to Pi as orthophosphate, whereas Nelson and Cox’s, Lehninger Principles of Biochemistry referred to it as HPO42–.

Acknowledgement: This question was provoked by the SE-Biology question — Where is the H+ ion in this step of glycolysis coming from?

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  • $\begingroup$ may be it is a gross stoichiometric term. A similar situation exists; where many school and college biology-textbooks write TCA cycle as 'citric acid', 'isocitric acid' etc (and accordingly sometimes draw structures as non-ionized acid groups). But all international books use terms like "citrate", "isocitrate", etc. and only draw their anionic forms. Thanks nice question. $\endgroup$ – Always Confused Nov 22 '16 at 16:29
  • $\begingroup$ May be because Pi lacks carbon (i.e. unlike ATP or GTP etc), so, called-as ''inorganic". However pyrophosphate or PP is also biologically important but it is not termed as Pi or inorganic phosphate $\endgroup$ – Always Confused Nov 22 '16 at 17:30
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    $\begingroup$ I think the umbrella term "inorganic phosphate" (Pi) was introduced as a shorthand for "phosphate dissolved in water", precisely because phosphate exists as both HPO4 and H2PO4 forms, as you mention --- it would be inaccurate to use only one formula, and it's inconvenient to have to use both. A similar shorthand is CO2(aq). It may be inaccurate for detailed enzymatic mechanisms, but it's sufficient for describing overall enzymatic reactions in water, and I would guess this is why it's still used. This is just my guess, haven't looking into this in depth ... $\endgroup$ – Roland Mar 4 '17 at 17:12
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    $\begingroup$ @Roland — I had started to do some historic back-tracking when nobody answered, but only got so far. I need to recall old books from the stack of my University library in order to get at the sources and have delayed until I have more time and energy. I'll post an answer to my own question eventually. $\endgroup$ – David Mar 4 '17 at 17:47
  • $\begingroup$ I'm voting to close this question as off-topic because it would be a better fit for history of science and mathematics (hsm.SE) $\endgroup$ – another 'Homo sapien' Mar 17 '17 at 7:16
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This terminology is at least as old as September 1944 when Enzymatic Synthesis of Acetyl Phosphate Journal of Biological Chemistry 155, 55-70 was published by Lipmann, which says:

Inorganic phosphate, referred to as Pi, was estimated colorimetrically

See also the definition of "inorganic phosphate" and "orthophosphate" from this 1943 University of Wisconsin Thesis:

Compound: Inorganic phosphate or orthophosphate

Definition: Phosphate whose calcium salt is insoluble in water-alcohol mixtures under the conditions to be described. E.G. NaH2PO4

In other words, "orthophosphate" was a generic term for mono, di, or tri basic phosphate. It did not have the narrower meaning attributed in the OP.

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  • $\begingroup$ Thank you for this piece of information which suggests an answer to the origin of the abbreviation, Pi, for inorganic phosphate. However it is interesting that in this paper Lilpmann does not use Pi in the biochemical equations he presents, but instead uses H.OPO3H2 (i.e H3PO4 — undissociated phosphoric acid). So I suspect that Pi was first used in equations subsequently, perhaps by Lipmann himself. Unless someone does it for me, I'll start to follow this up. $\endgroup$ – David Mar 25 '17 at 21:50
  • $\begingroup$ @David ok, start with equations 4 and 6 in this 1953 article: jbc.org/content/203/1/501.short $\endgroup$ – DavePhD Mar 25 '17 at 23:09
  • $\begingroup$ How do you find them? That's very interesting because in the list of abbreviations it defines Pi as orthophosphate, which is chemically precise, but ionically incorrect. However this is disguised (as it was for years) by the fact that the equations are "biochemical equations" and do not involve chemical formulae. I'll poke around a little next week in the hope that a comprehensive answer can be constructed. $\endgroup$ – David Mar 26 '17 at 10:50
  • $\begingroup$ @David I just searched in Google scholar scholar.google.com for terms like "inorganic phosphate" and "pi", or "orthophosphate" and "pi". $\endgroup$ – DavePhD Mar 26 '17 at 12:26
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    $\begingroup$ @David I think Wikipedia is just wrong about this and "orthophosphate" is a generic term for phosphoric acid and any salt thereof, but in contrast to metaphosphate, pyrophosphate, and polyphosphate. "Orthophosphate" has been used in this generic way for at least 150 years. $\endgroup$ – DavePhD Mar 26 '17 at 18:47

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