Disease relevance of Lignoceroyl-coenzyme A

• Peroxisomal lignoceroyl-CoA ligase deficiency in childhood adrenoleukodystrophy and adrenomyeloneuropathy [1].
• Adrenoleukodystrophy (X-ALD) is a demyelinating disorder characterized by the accumulation of saturated very-long-chain fatty acids (> C22:0) due to the impaired activity of lignoceroyl-CoA ligase [2].
• The enzyme activities of lignoceroyl-CoA ligase, acyl-CoA oxidase, bifunctional enzymes and acyl-CoA thiolase (individual peroxisomal beta-oxidation enzymes) after 90 min of ischemia were 87, 80, 87 and 85% of the control, respectively [3].

High impact information on Lignoceroyl-coenzyme A

• Determination of acyl-CoA ligase activities provided direct evidence that lignoceroyl-CoA ligase is deficient in peroxisomes while it is normal in mitochondrial and microsomes [1].
• This normal peroxisomal palmitoyl-CoA ligase activity as compared with the deficient activity of lignoceroyl-CoA ligase in C-ALD and AMN suggests the presence of two separate acyl-CoA ligases for palmitic and lignoceric acids in peroxisomes [1].
• Moreover, the normal oxidation of lignoceroyl-CoA as compared with the deficient oxidation of lignoceric acid in isolated peroxisomes also supports the conclusion that peroxisomal lignoceroyl-CoA ligase is impaired in both C-ALD and AMN [1].
• The very long chain lignoceroyl-CoA was also oxidized by palmitoyl-CoA oxidase and pristanoyl-CoA oxidase, the latter enzyme catalyzing approximately 65% of the total eluate activity [4].
• In spite of the observation that lignoceroyl-CoA ligase activity is present on the cytoplasmic surface of ER, our data indicate that lignoceroyl-CoA synthesized by ER is not available for oxidation in mitochondria [5].

Biological context of Lignoceroyl-coenzyme A

• Transfection of FATP4 cDNA into COS1 cells resulted in a 2-fold increase in palmitoyl-CoA synthetase (C16:0) and a 5-fold increase in lignoceroyl-CoA synthetase (C24:0) activity from membrane extracts, indicating that the FATP4 gene encodes an acyl-CoA synthetase with substrate specificity biased towards very long chain fatty acids [6].

Anatomical context of Lignoceroyl-coenzyme A

• We found enzyme-dependent formation of lignoceroyl-CoA in these same organelles (specific activities were 0.32 +/- 0.12, 0.86 +/- 0.12, and 0.78 +/- 0.07 nmol/h per mg protein, respectively) [5].
• However, lignoceroyl-CoA synthesis was inhibited by an antibody to palmitoyl-CoA ligase in isolated mitochondria while it was not inhibited in peroxisomes or endoplasmic reticulum (ER) [5].
• However, the inhibition in fibroblasts from patients with X-linked adrenoleukodystrophy, in which a specific defect of peroxisomal lignoceroyl-CoA synthetase was speculated, was similar to that in the controls [7].
• We have previously shown the existence of two separate enzymes for the synthesis of palmitoyl-CoA and lignoceroyl-CoA in rat brain microsomal membranes (1) [8].
• These results suggest that in addition to palmitoyl-CoA ligase, myelin also contains lignoceroyl-CoA ligase [9].

Associations of Lignoceroyl-coenzyme A with other chemical compounds

• Proteolytic enzyme treatment inhibited palmitoyl-CoA ligase activity in intact peroxisomes but had no effect on lignoceroyl-CoA ligase activity [10].
• A change from threonine-122 to alanine increased the substrate specificity in vitro for oleoyl-CoA and linoleoyl-CoA; whereas a change to leucine increased the substrate specificity for lignoceroyl-CoA [11].
• The synthesis of lignoceroyl-CoA from [1-14C]lignoceric acid and CoASH by this enzyme had an absolute dependence on ATP and Mg2+; ATP could not be replaced by GTP [I. Singh, M. S. Kang, and L. Phillips (1982) Fed. Proc. 41, 1192] [12].
• A time-related but unequal induction of acyl-CoA oxidases and catalase was observed with the 0.1% fenoprofen diet: at 21 d of treatment, the induction of lignoceroyl-CoA and palmitoyl-CoA oxidase activities were five-fold stronger than that of catalase activity [13].
• The activities of palmitoyl-CoA and lignoceroyl-CoA ligases in peroxisomes isolated from clofibrate-treated animals were 4.4- and 4.0-fold higher than those of the controls [14].

References