In situ measurements of enzyme activities in the brain

Kügler, P.

doi:10.1007/bf00159497

Cited by 20 publications

(6 citation statements)

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“…Indeed, oligodendroglial cells and neurons in culture can use D-,Q-hydroxybutyrate as a substrate for the generation of energy (Edmond et al, 1987) . The enzymes required for the disposal of the amino group of leucine, glutamate dehydrogenase (Kaneko et A., 1988;Kugler, 1993;Rothe et al, 1994) and glutamine synthetase (Norenberg and Martinez-Hernandez, 1979), are essentially restricted to astrocytes . Therefore, the breakdown of leucine is likely to be taking place in these cells, which forward the nitrogen-stripped metabolites to the neighboring cells as fuel material .…”

Section: Discussionmentioning

confidence: 99%

Generation of Ketone Bodies from Leucine by Cultured Astroglial Cells

Bixel

Hamprecht

1995

Journal of Neurochemistry

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To elucidate the significance of branched‐chain amino acids (BCAAs) for brain energy metabolism, the capacity to use BCAAs for oxidative metabolism was investigated in astroglia‐rich primary cultures derived from newborn rat brain. The cells selectively removed BCAAs from the culture medium, the disappearance following first‐order kinetics. The BCAAs disappeared rapidly in spite of the presence of sufficient glucose as substrate for the generation of energy. Taking into consideration that the ketogenic amino acid leucine could be degraded only to acetyl‐CoA and acetoacetate, and with the knowledge that astroglial cells have the capacity to secrete ketone bodies, this amino acid was chosen for further metabolic studies. After incubation of the cells with leucine, acetoacetate, d‐β‐hydroxybutyrate, and α‐ketoisocaproate were found to have accumulated in the culture medium. Identification of the radioactive metabolites generated from [4,5‐3H]leucine established that the source of the substances released was indeed leucine. These results indicate that, at least in culture, astroglial cells degrade leucine via the known metabolite α‐ketoisocaproate, to acetoacetate, which can be further reduced to d‐β‐hydroxybutyrate. It is hypothesized that upon release from brain astrocytes, the ketone bodies could serve as fuel molecules for neighboring cells such as neurons and oligodendrocytes. In view of these and other results, astrocytes may be considered the brain's fuel processing plants.

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Section: Discussionmentioning

confidence: 99%

Generation of Ketone Bodies from Leucine by Cultured Astroglial Cells

Bixel

Hamprecht

1995

Journal of Neurochemistry

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“…The reaction is catalysed by GABA transaminase (GABA-T) which is present in mitochondria of glial cells and neurons [138–140]. It is estimated that more than 90% of all GABA in the mammalian CNS is degraded in this way and contributes to energy metabolism in the tricarbonic acid cycle.…”

Section: Sequestration and Degradation Of Gabamentioning

confidence: 99%

GABA Metabolism and Transport: Effects on Synaptic Efficacy

2012

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GABAergic inhibition is an important regulator of excitability in neuronal networks. In addition, inhibitory synaptic signals contribute crucially to the organization of spatiotemporal patterns of network activity, especially during coherent oscillations. In order to maintain stable network states, the release of GABA by interneurons must be plastic in timing and amount. This homeostatic regulation is achieved by several pre- and postsynaptic mechanisms and is triggered by various activity-dependent local signals such as excitatory input or ambient levels of neurotransmitters. Here, we review findings on the availability of GABA for release at presynaptic terminals of interneurons. Presynaptic GABA content seems to be an important determinant of inhibitory efficacy and can be differentially regulated by changing synthesis, transport, and degradation of GABA or related molecules. We will discuss the functional impact of such regulations on neuronal network patterns and, finally, point towards pharmacological approaches targeting these processes.

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“…Recent studies revealed that GABA transaminase has an iron-sulfur cluster at the center of the GABA transaminase dimer (Storici et al, 2004). This enzyme is synthesized in postsynaptic neurons and astrocytes (reviewed in Kugler, 1993) and plays an essential role in the degradation of GABA, which is released from GABAergic synaptic terminals. Moreover, the inherent high neural activity in the above brain regions may cause an increased turnover of ironcontaining proteins, thereby creating a high demand for iron supply.…”

Section: Topography Of Nonheme Fe(iii) and Fe(ii) Distribution In Relmentioning

confidence: 99%