'''Pyrophosphatase''' (or '''inorganic pyrophosphatase''') is an enzyme that converts one molecule of [[pyrophosphate]] to two [[phosphate]] ions. This highly [[exergonic]] reaction (about -34KJ change in free energy) can be coupled to unfavorable biochemical transformations in order to drive these transformations to completion, as in [[Lipid metabolism|Lipid synthesis]] and other biochemical transformations.
'''Pyrophosphatase''' (or '''inorganic pyrophosphatase''') is an enzymethat one molecule of [[pyrophosphate]] to two [[phosphate]] ions.This highly [[exergonic]] reactioncan be coupled to unfavorable biochemical transformations in order to drive these transformations to completion, in [[metabolism|synthesis]] and
Pyrophosphatase (or inorganic pyrophosphatase) is an enzyme (EC126.96.36.199) that catalyzes the conversion of one molecule of pyrophosphate to two phosphate ions. This is a highly exergonic reaction, and therefore can be coupled to unfavorable biochemical transformations in order to drive these transformations to completion. The functionality of this enzyme plays a critical role in lipid metabolism (including lipid synthesis and degradation), calcium absorption and bone formation, and DNA synthesis, as well as other biochemical transformations.
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.
Examination of prokaryotic and eukaryotic forms of inorganic pyrophosphatase has shown that they differ significantly in both amino acid sequence, number of residues, and oligomeric organization. Despite differing structural components, recent work has suggested a large degree of evolutionary conservation of active site structure as well as reaction mechanism, based on kinetic data. Analysis of approximately one million genetic sequences taken from organisms in the Sargasso Sea identified a 57 residue sequence within the regions coding for inorganic pyrophosphatase that appears to be highly conserved; this region primarily consisted of the four early amino acid residues Gly, Ala, Val and Asp, suggesting an evolutionarily ancient origin for the protein.
↑Terkeltaub RA (July 2001). "Inorganic pyrophosphate generation and disposition in pathophysiology". Am. J. Physiol., Cell Physiol. 281 (1): C1–C11. PMID11401820.
↑Orimo H, Ohata M, Fujita T (September 1971). "Role of inorganic pyrophosphatase in the mechanism of action of parathyroid hormone and calcitonin". Endocrinology. 89 (3): 852–8. doi:10.1210/endo-89-3-852. PMID4327778.
↑Nelson, David L.; Cox, Michael M. (2000). Lehninger Principles of Biochemistry, 3rd ed. New York: Worth Publishers. p. 937. ISBN1-57259-153-6.
↑Ko KM, Lee W, Yu JR, Ahnn J (November 2007). "PYP-1, inorganic pyrophosphatase, is required for larval development and intestinal function in C. elegans". FEBS Lett. 581 (28): 5445–53. doi:10.1016/j.febslet.2007.10.047. PMID17981157.
↑McAlpine PJ, Mohandas T, Ray M, Wang H, Hamerton JL (1976). "Assignment of the inorganic pyrophosphatase gene locus (PP) to chromosome 10 in man". Cytogenet. Cell Genet. 16 (1–5): 201–3. doi:10.1159/000130590. PMID975879.
↑Sitnik TS, Avaeva SM (January 2007). "Binding of substrate at the effector site of pyrophosphatase increases the rate of its hydrolysis at the active site". Biochemistry Mosc. 72 (1): 68–76. doi:10.1134/s0006297907010087. PMID17309439.
↑Rodina EV, Vorobyeva NN, Kurilova SA, Belenikin MS, Fedorova NV, Nazarova TI (January 2007). "ATP as effector of inorganic pyrophosphatase of Escherichia coli. Identification of the binding site for ATP". Biochemistry Mosc. 72 (1): 93–9. doi:10.1134/s0006297907010117. PMID17309442.
↑Smirnova IN, Baĭkov AA (October 1983). "[Two-stage mechanism of the fluoride inhibition of inorganic pyrophosphatase using the fluoride ion]". Biokhimiia (in Russian). 48 (10): 1643–53. PMID6139128.CS1 maint: Unrecognized language (link)
↑Takahashi K, Inuzuka M, Ingi T (December 2004). "Cellular signaling mediated by calphoglin-induced activation of IPP and PGM". Biochem. Biophys. Res. Commun. 325 (1): 203–14. doi:10.1016/j.bbrc.2004.10.021. PMID15522220.