Acylcarnitine profile in tissues and body fluids of biotin‐deficient rats with and withoutl‐carnitine supplementation

Summary Since biotin‐deficient (BD) rats are a good animal model for human multiple carboxylase deficiency and have low plasma free carnitine levels, short‐chain acylcarnitine profiles in biotin‐deficient rats withl‐carnitine supplementation (BDC rats) and BD rats were investigated by fast‐atom bombardment and tandem mass spectrometry and gas chromatography/mass spectrometry. By the latter method, 3‐hydroxyisovalerylcarnitine was identified in BD rats, and showed the greatest accumulation among short‐chain acylcarnitines in tissues of BD rats, while the tissue levels of propionic acid were more markedly elevated than those of 3‐hydroxyisovaleric acid. The tissue levels of 3‐hydroxyisovaleryl‐carnitine were significantly lower and those of propionyl‐carnitine were somewhat higher in BDC rats than in BD rats, while the tissue levels of propionic acid and 3‐hydroxyisovaleric acid in BDC rats were lower than those in BD rats. These changes were more apparent in kidney than in other tissues. The amounts of urinary excretion of acylcarnitines were markedly larger, and those of 3‐hydroxyisovaleric acid were somewhat smaller in BDC rats than in BD rats, while those of propionic acid were very low in BD and BDC rats as compared with those of 3‐hydroxyisovaleric acid. It seems that the relationship between the concentrations of 3‐hydroxyisovalerylcarnitine and those of propionylcarnitine reflects the unique metabolism of the related metabolites in tissues, especially in kidney, which may be influenced by their urinary excretion and the availability of free carnitine. These data in biotin deficiency suggest that carnitine supplementation is possibly beneficial for patients with holocarboxylase synthetase deficiency who respond incompletely to biotin therapy.