INHIBITION OF CARNITINE PALMITOYLTRANSFERASE IN NORMAL HUMAN SKELETAL-MUSCLE AND IN MUSCLE OF PATIENTS WITH CARNITINE PALMITOYLTRANSFERASE DEFICIENCY BY LONG-CHAIN AND SHORT-CHAIN ACYLCARNITINE AND ACYL-COENZYME-A
S. Zierz et al., INHIBITION OF CARNITINE PALMITOYLTRANSFERASE IN NORMAL HUMAN SKELETAL-MUSCLE AND IN MUSCLE OF PATIENTS WITH CARNITINE PALMITOYLTRANSFERASE DEFICIENCY BY LONG-CHAIN AND SHORT-CHAIN ACYLCARNITINE AND ACYL-COENZYME-A, The Clinical investigator, 71(10), 1993, pp. 763-769
The inhibition of total carnitine palmitoyltransferase (CPT) by short-
and long-chain acylcarnitine and acyl-coenzyme A (acyl-CoA) was studi
ed in muscle homogenates of normal controls and of five new patients w
ith CPT deficiency using the isotope forward assay. Acetylcarnitine in
hibited neither normal CPT activity nor the CPT of patients. D,L-Palmi
toylcarnitine almost completely inhibited CPT in patients but only 55%
of normal activity. In controls the CPT fraction sensitive to inhibit
ion by palmitoylcarnitine appeared to be identical with the fraction s
ensitive to inhibition by malonyl-CoA and succinyl-CoA, which probably
represents CPT II. The abnormal inhibition of CPT by palmitoylcamitin
e was more likely due to product inhibition than to a detergent effect
. Acetyl-CoA concentrations up to 0.4 mM and palmitoyl-CoA above optim
al substrate concentrations up to 0.3 mM both inhibited normal CPT by
about 25%, whereas the CPT of patients was significantly more inhibite
d by both substances than was normal CPT. The inhibition by acetyl-CoA
was probably due to the structural relationship with malonyl-CoA and
succinyl-CoA. The abnormal inhibition of CPT in patients by palmitoyl-
CoA was due either to an abnormal substrate inhibition or to a deterge
nt effect on CPT II similar to that of Triton X-100. The data indicate
that in CPT deficiency total CPT activity is normal under optimal ass
ay conditions. CPT II, however, is abnormally inhibited by fatty acid
metabolites that accumulate during fasting.