Growth of the virulent human malaria parasite Plasmodium falciparum is dependent on an extracellular supply of pantothenate (vitamin B(5)) and is susceptible to inhibition by pantothenate analogues that hinder pantothenate utilization. In this study, on the hunt for pantothenate analogues with increased potency relative to those reported previously, we screened a series of pantothenamides (amid...

The malaria-causing blood stage of Plasmodium falciparum requires extracellular pantothenate for proliferation. The parasite converts pantothenate into coenzyme A (CoA) via five enzymes, the first being a pantothenate kinase (PfPanK). Multiple antiplasmodial pantothenate analogues, including pantothenol and CJ-15,801, kill the parasite by targeting CoA biosynthesis/utilisation. Their mechanism ...

Pantothenate kinase-associated neurodegeneration (PKAN), a rare neurological disorder occurs by variation(s) in the PANK2 (Pantothenate kinase 2) gene and is linked to iron accumulation basal ganglia. The researchers have carried out targeted sequencing of all exons patient with suspected phenotype PKAN. A missense variant exon 6 (NM_153638.3:c.1583C>T,NP_705902.2:p.Thr528Met) has been ident...

Pantothenate kinase-associated neurodegeneration (formerly Hallervorden-Spatz syndrome), the most prevalent form of neurodegeneration with brain iron accumulation, is a rare degenerative brain disease characterised by predominantly extrapyramidal dysfunction resulting from mutations in the PANK2 (pantothenate kinase 2) gene. Using DNA mutation analysis, the authors identified a novel missense m...

Biomimicry valuably allows the understanding of the essential chemical components required to recapitulate biological function, yet direct strategies for evaluating the roles of amino acids in proteins can be limited by access to suitable, subtly-altered unnatural variants. Here we describe a strategy for dissecting the role of histidine residues in enzyme active sites using unprecedented, chem...

Coenzyme A (CoA) is an ubiquitous and essential cofactor, synthesized from the precursor pantothenate. Vitamin biosynthetic pathways are normally tightly regulated, including the pathway from pantothenate to CoA. However, no regulation of pantothenate biosynthesis has been identified. We have recently described an additional component in the pantothenate biosynthetic pathway, PanZ, which promot...

1. The effects of incorporation of copper sulphate supplying 250 mg copper/kg semi-purified diet with graded amounts of calcium pantothenate (CaPa) were studied in chicks. 2. When the doses of CaPa were marginally adequate or less the Cu supplementation induced severe signs of pantothenic acid (PaA) deficiency. 3. Livers of the Cu-treated birds given low doses of PaA had lower concentrations of...

Although several workers have observed that the bacteriostatic effect of salicylate can be reversed by pantothenate, there is disagreement about the reaction step affected. Salicylate has been considered to inhibit synthesis of pantoate (Ivanovics, 1942), the conversion of pantoate to pantothenate (Roblin, 1949), and the utilization of pantothenate (Mcllwain, 1943; Work and Work, 1948); Ackeima...

During work on coenzyme A (CoA), a method for the liberation of pantothenic acid from the coenzyme was worked out (1). The method involves the use of a combination of two enzymes; namely, intestinal phosphatase and an enzyme extractable from acetone powder of bird liver (chicken (2), duck, or pigeon). This procedure proved the most efficient pretreatment to liberate bound vitamin under conditio...