The Control of Cardiac Adenine Nucleotides: The Discovery and Potential Function of High-Energy Oligomeric Derivatives of ATP

Mowbray, John

doi:10.1007/978-1-4615-3894-3_21

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“…The product of this enzyme is the monomeric unit of (PG-ATP),, 3-phosphoglyceroyl-y-triphospho(5')adenosine. This can be cleaved by snake venom phosphodiesterase I to yield ADP [S]; then the ADP can be converted by pyruvate kinase to ATP which can be assayed by luciferin and luciferase (see [18]). When this assay was attempted the enzyme as purified was found to have tightly bound polymeric substrate leading to high blank values: not all of this nucleotide material was released when Table 4.…”

Section: The Estimation Of (Pg-atp)n In Heartsmentioning

confidence: 99%

Evidence that the recently discovered high‐energy nucleotide derivative, oligo(phosphoglyceroyl‐ATP) forms the end chains of purinogen, a complex polymeric major stroage form of adenine nucleotide and phosphate in heart

Patel

Sarcina

Mowbray

1994

European Journal of Biochemistry

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Previous work in our laboratory has shown that free adenine nucleotides in heart, liver and kidney exchange rapidly with a major acid-insoluble species which we have characterised as oligo[3-phospho-glyceroyl-y-triphospho(5')adenosine(3')], abbreviated to (PG-ATP),. This has been found in liver and in heart to be complexed to a specific 3'-phosphodiesterase which releases PG-ATP monomers and is located in mitochondrial inter-membrane space. In ['4C]adenosine-perfused hearts, (PG-ATP), has been shown to reach specific radioactivity equilibrium with free ATP within 30 min. Attempts to estimate the quantities of nucleotide in (PG-ATP), and free nucleotides in response to a variety of stimuli using previously labelled hearts showed by contrast that the free and sequestered nucleotide pools were not at equilibrium. Re-examination of the rapidly labelled acid-insoluble species led to the recognition of radioactive inhomogeneity and of three additional nucleotide components. Perfusion of hearts with phosphate-free medium increased the proportion of 14C incorporated into the sequestered form by 70% and caused the net transfer of 0.9 pmol . g-' of purine from free adenine nucleotides to the sequestered form. The findings point to the existence of a more complex polymer whose rapidly exchanging end chains we had previously isolated and characterised as (PG-ATP),; we suggest the name purinogen for this polymer and show that it can contain between 25 % and 55 % of the tissue nucleotide pool in rat heart. Large changes in the amounts of adenine nucleotides extracted at different times from steady-state perfused rat hearts could not be explained by interconversion with known derivatives or polymers and led us to propose that some unknown major source of nucleotides capable of rapid exchange with the known nucleotides must exist in heart [l -31. Labelling studies located a trichloroacetic acidmethanol-precipitable species which .rapidly exchanged units with ATP in rat heart [4], kidney [5] and liver [6]. Selective digestion and chromatography, along with "P-NMR and mass spectrometry studies, led us to propose a structure and the name of oligo-(phosphoglyceroyl-ATP) (PG-ATP), for this compound [7]. In subsequent work we have purified from liver a specific 3'-phosphodiesterase which releases 3-phospho-glyceroyl-ytriphospho(5')adenosine (PG-ATP) units [8] : furthermore in liver and heart, this enzyme is found only in mitochondrial intermembrane space [8] tightly complexed with its substrate [9], suggesting that (PG-ATP), may be exclusively located there too.In perfused rat hearts the acid-insoluble species was observed to reach specific activity equilibrium with [8-I4C]ATP Correspondence to J. Mowbray,

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Section: The Estimation Of (Pg-atp)n In Heartsmentioning

confidence: 99%