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J Biol Chem, Vol. 275, Issue 2, 1377-1383, January 14, 2000
From the Pantothenate kinase (PanK) is the key regulatory
enzyme in the CoA biosynthetic pathway in bacteria and is thought to
play a similar role in mammalian cells. We examined this hypothesis by
identifying and characterizing two murine cDNAs that encoded PanK.
The two cDNAs were predicted to arise from alternate splicing of
the same gene to yield different mRNAs that encode two isoforms (mPanK1 The nucleotide sequence(s) reported in this paper has been submitted to the GenBankTM/EMBL Data Bank with accession number(s) AF200357.
Pantothenate Kinase Regulation of the Intracellular
Concentration of Coenzyme A*
§,,, and§¶
Department of Biochemistry, St. Jude
Children's Research Hospital, Memphis, Tennessee 38105 and the
§ Department of Biochemistry, University of Tennessee,
Memphis, Tennessee 38163
and mPanK1
) with distinct amino termini. The predicted protein sequence of mPanK1 was not related to bacterial PanK but exhibited significant similarity to Aspergillus nidulans
PanK. mPanK1 was most highly expressed in heart and kidney, whereas mPanK1 mRNA was detected primarily in liver and kidney.
Pantothenate was the most abundant pathway component (42.8%) in normal
cells providing clear evidence that pantothenate phosphorylation was a
rate-controlling step in CoA biosynthesis. Enhanced mPanK1 expression eliminated the intracellular pantothenate pool and triggered
a 13-fold increase in intracellular CoA content. mPanK1 activity
in vitro was stimulated by CoA and strongly inhibited by
acetyl-CoA illustrating that differential modulation of mPanK1 activity by pathway end products also contributed to the management of
CoA levels. These data support the concept that the expression and/or
activity of PanK is a determining factor in the physiological regulation of the intracellular CoA concentration.
*
This work was supported by National Institutes of Health
Grants GM 45737 (to S. J.) and GM34496 (to C. O. R.), Cancer Center (CORE) Support Grant CA 21765, and the American Lebanese Syrian Associated Charities.The costs of publication of this
article were defrayed in part by the
payment of page charges. The article must therefore be hereby marked
"advertisement" in
accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
Copyright © 2000 by The American Society for Biochemistry and Molecular Biology, Inc.
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