How pantothenol intervenes in Coenzyme-A biosynthesis of Mycobacterium tuberculosis

Kumar, Parimal ; Chhibber, Manmohan ; Surolia, Avadhesha (2007) How pantothenol intervenes in Coenzyme-A biosynthesis of Mycobacterium tuberculosis Biochemical and Biophysical Research Communications, 361 (4). pp. 903-909. ISSN 0006-291X

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Coenzyme A is an indispensable cofactor for all organisms and holds a central position in a number of pathways. Prokaryotic enzymes involved in the synthesis of CoA are quite different from their mammalian counterparts; hence, they are good targets for the development of antimicrobials to treat many diseases. There are antimicrobials that act by inhibiting CoA biosynthesis. It has been suggested that pantothenol exhibits antibacterial activity by competitively inhibiting pantothenate kinase, a key regulatory enzyme for CoA synthesis. Contrary to these suggestions, in this paper, we demonstrate that pantothenol acts as a substrate for Mycobacterium tuberculosis and Escherichia coli pantothenate kinases. The product, 4'-phosphopantothenol, thus formed inhibits competitively the utilization of 4'-phosphopantothenate by CoaBC. Thus, it is the failure of CoaBC to utilize 4'-phosphopantothenol as a substrate that accounts for the bactericidal activity of pantothenol.

Item Type:Article
Source:Copyright of this article belongs to Elsevier Science.
Keywords:Pantothenol; Pantothenate Kinase; Coenzyme A; Isothermal Titration Calorimetry; Mycobacterium tuberculosis; 4'-Phosphopantothenate; Pantothenate
ID Code:56460
Deposited On:24 Aug 2011 11:34
Last Modified:24 Aug 2011 11:34

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