Physiological roles of the pantothenate kinases

Abstract

CoA (coenzyme A) is an essential cofactor that is involved in many metabolic processes. CoA is derived from pantothenate in five biosynthetic reactions. The CoA biosynthetic pathway is regulated by PanKs (pantothenate kinases) and four active isoforms are expressed in mammals. The critical physiological functions of the PanKs are revealed by systematic deletion of the Pank genes in mice.

Figure 1. Mouse tissue steady-state CoA levels

(A) Wild-type mice (male, three or four per group), 8–12 weeks of age, were fed ad libitum on chow containing 6 % fat. Tissues were removed, snap frozen and extracted for CoA measurement. Data were normalized to tissue wet weight. Animal handling procedures were approved under protocol 323 by the St. Jude Institutional Animal Care and Use Committee. (B) Duplicate adherent cell cultures were harvested at late logarithmic growth and prepared for CoA measurements. Data were normalized to viable cell numbers for each culture.

Figure 2. Mouse Pank gene expression profiles

Wild-type mice (male, three to four per group), 8–12 weeks of age, were fed ad libitum. Tissues were removed and stored frozen in RNAlater (Ambion). RNA was isolated and prepared for quantitative real-time reverse transcription–PCR. Data were normalized to GAPDH (glyceraldehyde-3-phosphate dehydrogenase) expression and the value for Pank1 transcripts was set at 1.0. Animal handling procedures were approved under protocol 323 by the St. Jude Institutional Animal Care and Use Committee.