Defect in biosynthesis of mitochondrial acetoacetyl-coenzyme A thiolase in cultured fibroblasts from a boy with 3-ketothiolase deficiency.

S Yamaguchi; T Orii; N Sakura; S Miyazawa; T Hashimoto

doi:10.1172/JCI113388

Department of Pediatrics, Gifu University School of Medicine, Japan.

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Department of Pediatrics, Gifu University School of Medicine, Japan.

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Department of Pediatrics, Gifu University School of Medicine, Japan.

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Department of Pediatrics, Gifu University School of Medicine, Japan.

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Department of Pediatrics, Gifu University School of Medicine, Japan.

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Published in Volume 81, Issue 3 on March 1, 1988
J Clin Invest. 1988;81(3):813–817. https://doi.org/10.1172/JCI113388.
© 1988 The American Society for Clinical Investigation

Published March 1, 1988 - Version history

The etiology of 3-ketothiolase deficiency has been attributed to a defect of mitochondrial acetoacetyl-CoA thiolase because the acetoacetyl-CoA thiolase activity in related materials is not activated by K+, a property characteristic for this enzyme. We studied the enzyme protein and the biosynthesis of mitochondrial acetoacetyl-CoA thiolase, using cultured skin fibroblasts from a 5-yr-old boy with 3-ketothiolase deficiency. The following results were obtained. (a) Activation of acetoacetyl-CoA thiolase activity by K+ was nil; (b) The enzyme activity was not affected by treatment with the antibody against mitochondrial acetoacetyl-CoA thiolase; (c) A signal for mitochondrial acetoacetyl-CoA thiolase protein was not detected in the immunoblot analysis; and (d) Pulse-chase experiments of skin fibroblasts, using [35S]methionine, revealed no incorporation of radioactivity into this enzyme. Therefore, fibroblasts from this patient lacked mitochondrial acetoacetyl-CoA thiolase protein due to a defect in its biosynthesis.

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