Abstract
Ketone bodies acetoacetate and 3-hydroxy-n-butyric acid are metabolites derived from fatty acids and ketogenic amino acids such as leucine. They are mainly produced in the liver via reactions catalyzed by the ketogenic enzymes mitochondrial 3-hydroxy-3-methylglutary-coenzyme A synthase and 3-hydroxy-3-methylglutary-coenzyme A lyase. After prolonged starvation, ketone bodies can provide up to two-thirds of the brain’s energy requirements. The rate-limiting enzyme of ketone body utilization (ketolysis) is succinyl-coenzyme A:3-oxoacid coenzyme A transferase. The subsequent step of ketolysis is catalyzed by 2-methylactoacetyl-coenzyme A thiolase, which is also involved in isoleucine catabolism. Inborn errors of metabolism affecting those four enzymes are presented and discussed in the context of differential diagnoses. While disorders of ketogenesis can present with hypoketotic hypoglycemia, inborn errors of ketolysis are characterized by metabolic decompensations with ketoacidosis. If those diseases are considered early and appropriate treatment is initiated without delay, patients with inborn errors of ketone body metabolism often have a good clinical outcome.
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Acknowledgments
The author is grateful to Professor Toshiyuki Fukao (Gifu, Japan) for his introduction into the field of inborn errors of ketone body utilization, long-time collaboration, and critical reading of the manuscript. Dr. Sarah Grünert (Freiburg, Germany) is thanked for valuable suggestions as are the members of the Freiburg Laboratory for Clinical Biochemistry and Metabolism for continuous diagnostic and research effort in the area of ketone body metabolism and beyond.
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Communicated by: Matthias Baumgartner
Competing interest: None declared.
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Sass, J.O. Inborn errors of ketogenesis and ketone body utilization. J Inherit Metab Dis 35, 23–28 (2012). https://doi.org/10.1007/s10545-011-9324-6
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DOI: https://doi.org/10.1007/s10545-011-9324-6