Document Detail

Turnover of inositol polyphosphate pyrophosphates in pancreatoma cells.
MedLine Citation:
PMID:  8382679     Owner:  NLM     Status:  MEDLINE    
There is little information concerning the intracellular function of inositol 1,3,4,5,6-pentakis- and hexakisphosphate, despite their being the most abundant inositol polyphosphates. Current opinions that they play passive roles as antioxidants (Graf, E., Mahoney, J. R., Bryant, R. G., and Eaton, J. W. (1987) J. Biol. Chem. 259, 3620-3624) or "housekeeping" molecules (Berridge, M. J., and Irvine, R. F. (1989) Nature 341, 197-205) arises from belief in their metabolic lethargy. However, we have discovered that cell homogenates, incubated with 5 mM fluoride and 5 mM ATP, converted both inositol hexakisphosphate (Km = 2 +/- 0.5 microM, Vmax = 9 +/- 2 pmol/mg of protein/min) and inositol 1,3,4,5,6-pentakisphosphate (Km = 13 +/- 4 microM, Vmax = 11 +/- 5 pmol/mg of protein/min) to more polar products. These reactions were also observed in intact cells treated with 0.5-20 mM fluoride, and the precursor/product relationships were confirmed by comparing the effects of fluoride on cells differentially labeled with [3H]inositol in either short-term or pulse-chase protocols. The novel products were determined to be inositol pyrophosphates because of their relatively specific hydrolysis by tobacco pyrophosphatase and alkaline phosphatase. The pyrophosphates were metabolized rapidly by cell homogenates back to their pentakisphosphate and hexakisphosphate precursors. This endogenous pyrophosphatase activity was inhibited by up to 99% by 5 mM fluoride in vitro. In intact cells incubated with 10 mM fluoride, about 20% of the inositol 1,3,4,5,6-pentakisphosphate pool, and 50% of the inositol hexakisphosphate pool were each converted to pyrophosphate derivatives within 1 h.
F S Menniti; R N Miller; J W Putney; S B Shears
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  268     ISSN:  0021-9258     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  1993 Feb 
Date Detail:
Created Date:  1993-03-26     Completed Date:  1993-03-26     Revised Date:  2013-02-11    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  3850-6     Citation Subset:  IM    
Calcium Regulation Section, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina 27709.
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MeSH Terms
Antimycin A / analogs & derivatives,  pharmacology
Diphosphates / metabolism*
Fluorides / pharmacology
Inositol Phosphates / chemistry,  metabolism*
Molecular Structure
Pancreatic Neoplasms
Phytic Acid / metabolism
Tumor Cells, Cultured
Type C Phospholipases / metabolism
Reg. No./Substance:
0/Diphosphates; 0/Fluorides; 0/Inositol Phosphates; 11118-72-2/antimycin; 25663-09-6/inositol pentaphosphate; 642-15-9/Antimycin A; 83-86-3/Phytic Acid; EC 3.1.4.-/Type C Phospholipases

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