The murine pantothenate kinase (Pank1) gene encodes two differentially regulated pantothenate kinase isozymes

Pantothenate kinase (PanK) is a rate-determining enzyme in coenzyme A (CoA) biosynthesis. The mouse murine pantothenate kinase (Pank1) gene consists of seven introns and eight exons and is located on chromosome 19 (19C2-3). Two biochemically distinct PanK1 protein isoforms, PanK1alpha and PanK1beta, are encoded by the Pank1 gene. Both proteins have the same 363 amino acid catalytic domain encoded by exons 2 through 7. The PanK1beta transcript begins with exon 1beta and translates into a ten-residue amino terminus plus the catalytic domain. The PanK1alpha. transcript initiates at an alternate upstream site at exon 1alpha which is spliced with exon 2, excluding exon 1beta. Exon 1alpha encodes a 184-residue regulatory domain at the amino terminus of the PanK1alpha protein that confers feedback inhibition by free CoA and long-chain acyl-CoA, and increases the regulation of PanK enzyme activity by acetyl-CoA and malonyl-CoA. Differential expression of the PanK1alpha and PanK1beta transcripts would alter the amount of CoA produced in cells as a function of the ratio of free CoA to acetyl-CoA, a reflection of the metabolic status of the tissue. (C) 2002 Elsevier Science B.V. All lights reserved.