Hexose transport properties of myoblasts isolated from a patient with suspected muscle carnitine deficiency

Abstract

The human primary carnitine deficiency syndromes are potentially fatal disorders affecting children and adults. The molecular etiologies of these syndromes have not been fully determined. Muscle carnitine deficiency syndrome is characterized by mild to severe muscle weakness, lipid accumulation in muscle, and reduced muscle carnitine concentration. In the present investigation, the hexose transport properties of muscle cells isolated from a patient with suspected muscle carnitine deficiency (MCD) were examined. We have previously shown that myoblasts from normal human subjects possessed at least two hexose transport systems, the low (LAHT) and the high (HAHT) affinity hexose transport systems. Their preferred substrates were 3-O-methyl-D-glucose and 2-deoxyglucose (dGlc), respectively; HAHT, but not LAHT, was sensitive to inhibition by carbonyl cyanide m-chlorophenylhydrazone (CCCP). Here we show that the kinetic properties of HAHT in the MCD myoblasts differ significantly from those of normal myoblasts and that the rates of dGlc transport by MCD myoblasts are restored to normal by growth in 40 microM L-carnitine. We also demonstrate that the kinetic properties of LAHT are quite similar in both normal and MCD myoblasts. It can be inferred from these findings that HAHT and LAHT may be coded or regulated by different genes. Based on the finding that the dGlc transport system in L-carnitine grown cells is no longer sensitive to inhibition by CCCP, it is thought that L-carnitine may play a regulatory role in HAHT, viz., by maintaining the HAHT transporter in a functional state, even in energy-uncoupled cells.(ABSTRACT TRUNCATED AT 250 WORDS)