ENHANCED SYNTHESIS OF HEXACOSANOIC ACID IN THE CULTURED FIBROBLASTS FROM PATIENTS WITH　ADRENOLEUKODYSTROPHY

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We previously demonstrated the increased activity of fatty acid elongation in the microsomal fraction of adrenoleukodystrophy (ALD) fibroblasts. In the present study, detailed pathways for the synthesis of hexacosanoic acid (C26:0) were delineated using deuterium labeling and mass fragmentography. Replacement rate or fractional turnover rate of C26:0 in ALD fibroblasts increased by 67% of the control, while the rate of replacement from C16:0 to C24:0 decreased in ALD. This may indicate an activation of fatty acid synthesis specific for C26:0. When two elongation activities using endogenously formed precursors and exogenous or preexisting fatty acids were separately measured in ALD, elongation products starting from exogenous fatty acids increased in C16:0, C18:0, C20:0, C22:0 and C24:0, but the corresponding fraction in C26:0 decreased as compared to the control. These results suggest that the synthesis of C26:0 may take place in a compartment different from those for the synthesis of fatty acids whose chains are shorter than C26:0, and that the activity of C26:0 synthesis is enhanced in vivo in ALD.