Inorganic Pyrophosphatase - Biological Function and Significance

Biological Function and Significance

The hydrolysis of inorganic pyrophosphate (PPi) to two phosphate ions is utilized in many biochemical pathways to render reactions effectively irreversible. This process is highly exergonic (accounting for approximately a −19kJ change in free energy), and therefore greatly increases the energetic favorability of reaction system when coupled with a typically less-favorable reaction.

Inorganic pyrophosphatase catalyzes this hydrolysis reaction in the early steps of lipid degradation, a prominent example of this phenomenon. By promoting the rapid hydrolysis of pyrophosphate (PPi), Inorganic pyrophosphatase provides the driving force for the activation of fatty acids destined for oxidation.

Before fatty acids can undergo degradation to fulfill the metabolic needs of an organism, they must first be activated via a thioester linkage to coenzyme A. This process is catalyzed by the enzyme acyl CoA synthetase, and occurs on the outer mitochondrial membrane. This activation is accomplished in two reactive steps: (1) the fatty acid reacts with a molecule of ATP to form an enzyme-bound acyl adenylate and pyrophosphate (PPi), and (2) the sulfhydryl group of CoA attacks the acyl adenylate, forming acyl CoA and a molecule of AMP. Each of these two steps is reversible under biological conditions, save for the additional hydrolysis of PPi by inorganic pyrophosphatase. This coupled hydrolysis provides the driving force for the overall forward activation reaction, and serves as a source of inorganic phosphate used in other biological processes.