Pyrophosphate - in Biochemistry

In Biochemistry

Pyrophosphates are very important in biochemistry. The anion P₂O₇4− is abbreviated PP_i and is formed by the hydrolysis of ATP into AMP in cells.

ATP → AMP + PP_i

For example, when a nucleotide is incorporated into a growing DNA or RNA strand by a polymerase, pyrophosphate (PP_i) is released. Pyrophosphorolysis is the reverse of the polymerization reaction in which pyrophosphate reacts with the 3'-nucleotidemonophosphate (NMP or dNMP), which is removed from the oligonucleotide to release the corresponding triphosphate (dNTP from DNA, or NTP from RNA).

The pyrophosphate anion has the structure P₂O₇4−, and is an acid anhydride of phosphate. It is unstable in aqueous solution and hydrolyzes into inorganic phosphate:

P₂O₇4− + H₂O → 2 HPO₄2−

or in biologists' shorthand notation:

PP_i + H₂O → 2 P_i

In the absence of enzymic catalysis, hydrolysis reactions of simple polyphosphates such as pyrophosphate, linear triphosphate, ADP, and ATP normally proceed extremely slowly in all but highly acidic media.

(The reverse of this reaction is a method of preparing pyrophosphates by heating phosphates.)

This hydrolysis to inorganic phosphate effectively renders the cleavage of ATP to AMP and PP_i irreversible, and biochemical reactions coupled to this hydrolysis are irreversible as well.

PP_i occurs in synovial fluid, blood plasma, and urine at levels sufficient to block calcification and may be a natural inhibitor of hydroxyapatite formation in extracellular fluid (ECF). Cells may channel intracellular PP_i into ECF. ANK is a nonenzymatic plasma-membrane PP_i channel that supports extracellular PP_i levels. Defective function of the membrane PP_i channel ANK is associated with low extracellular PP_i and elevated intracellular PP_i. Ectonucleotide pyrophosphatase/phosphodiesterase (ENPP) may function to raise extracellular PP_i.

From the standpoint of high energy phosphate accounting, the hydrolysis of ATP to AMP and PP_i requires two high-energy phosphates, as to reconstitute AMP into ATP requires two phosphorylation reactions.

AMP + ATP → 2 ADP

2 ADP + 2 P_i → 2 ATP