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Cerebral ketone body metabolism
Abstract
Summary: Ketone bodies (KBs) are an important source of energy for the brain. During the neonatal period, they are also precursors for the synthesis of lipids (especially cholesterol) and amino acids. The rate of cerebral KB metabolism depends primarily on the concentration in blood; high concentrations occur during fasting and on a high‐fat diet. Cerebral KB metabolism is also regulated by the permeability of the blood–brain barrier (BBB), which depends on the abundance of monocarboxylic acid transporters (MCT1). The BBB's permeability to KBs increases with fasting in humans. In rats, permeability increases during the suckling period, but human neonates have not been studied. Monocarboxylic acid transporters are also present in the plasma membranes of neurons and glia but their role in regulating KB metabolism is uncertain. Finally, the rate of cerebral KB metabolism depends on the activities of the relevant enzymes in brain. The activities vary with age in rats, but reliable results are not available for humans. Cerebral KB metabolism in humans differs from that in the rat in several respects. During fasting, for example, KBs supply more of the brain's energy in humans than in the rat. Conversely, KBs are probably used more extensively in the brain of suckling rats than in human neonates. These differences complicate the interpretation of rodent studies. Most patients with inborn errors of ketogenesis develop normally, suggesting that the only essential role for KBs is as an alternative fuel during illness or prolonged fasting. On the other hand, in HMG‐CoA lyase deficiency, imaging generally shows asymptomatic white‐matter abnormalities. The ability of KBs to act as an alternative fuel explains the effectiveness of the ketogenic diet in GLUT1 deficiency, but its effectiveness in epilepsy remains unexplained.
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Citations
Cited by
Anticonvulsant Mechanisms of the Ketogenic Diet
Bough, K. J., & Rho, J. M. (2007) · Epilepsia · doi:10.1111/j.1528-1167.2007.00915.x · Cited by 523
Schönfeld, P., & Reiser, G. (2013) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1038/jcbfm.2013.128 · Cited by 457
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“In this example, the mechanism is unnown, but the reduced epileptic seizures under fasting onditions, when ketone bodies provide the energy for the rain, suggest that an altered energy supply may be intrumental ( Morris, 2005 ).”
BackgroundFalkowska, A., Gutowska, I., Goschorska, M., Nowacki, P., Chlubek, D., & Baranowska-Bosiacka, I. (2015) · International Journal of Molecular Sciences · doi:10.3390/ijms161125939 · Cited by 277
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Rose, J., Brian, C., Pappa, A., Panayiotidis, M. I., & Franco, R. (2020) · Frontiers in Neuroscience · doi:10.3389/fnins.2020.536682 · Cited by 196
Yao, J., Chen, S., Mao, Z., Cadenas, E., & Brinton, R. D. (2011) · PLoS ONE · doi:10.1371/journal.pone.0021788 · Cited by 169
“While the normal brain exclusively relies on glucose for energy production [1,25], under long-term starvation or certain disease conditions, the brain can use alternative substrates, such as ketone bodies, for ATP generation [18,20,26].”
BackgroundFasting is neuroprotective following traumatic brain injury
Davis, L. M., Pauly, J. R., Readnower, R. D., Rho, J. M., & Sullivan, P. G. (2008) · Journal of Neuroscience Research · doi:10.1002/jnr.21628 · Cited by 149
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Managing diabetes in preschool children
Sundberg, F., Barnard, K., Cato, A., de Beaufort, C., DiMeglio, L. A., Dooley, G., Hershey, T., Hitchcock, J., Jain, V., Weissberg-Benchell, J., et al. (2017) · Pediatric Diabetes · doi:10.1111/pedi.12554 · Cited by 91
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Ketogenic diets and Alzheimer’s disease
Lange, K. W., Lange, K. M., Makulska-Gertruda, E., Nakamura, Y., Reissmann, A., Kanaya, S., & Hauser, J. (2017) · Food Science and Human Wellness · doi:10.1016/j.fshw.2016.10.003 · Cited by 56
Peralta, S., Torraco, A., Wenz, T., Garcia, S., Diaz, F., & Moraes, C. T. (2014) · Human Molecular Genetics · doi:10.1093/hmg/ddt526 · Cited by 42
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Metadata
- Authors
- Morris, A. A. M.
- Venue
- Journal of Inherited Metabolic Disease
- Publisher
- Wiley
- Published
- 2004-08-13
- Volume
- 28
- Issue
- 2
- Pages
- 109-121
- ISSN
- 0141-8955 (ISSN-L)
- 1573-2665
- OpenAlex
- W2045614704
- Cited by
- 298
- References
- 0
- FWCI
- 4.56
- Type
- journal article
- Language
- en
- Open access
- closed
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