Energy Metabolism in Conformational Diseases

Biosimulation in Drug Development. Edited by Martin Bertau, Erik Mosekilde, and Hans V. Westerhoff Copyright 2008 WILEY-VCH Verlag GmbH Co. KGaA, Weinheim ISBN 978-3-527-31699-1 

The ANLSH challenged the classic view [2, 3]. It postulates compartmentaliza-tion of brain lactate metabolism between neurons and astrocytes the activity-induced uptake of glucose takes place predominantly in astrocytes, which metabolize glucose anaerobically. Lactate produced from anaerobic glycolysis in astrocytes is then released from astrocytes and provides the primary metabolic fuel for neurons. The increased lactate in the neurons is converted to pyruvate via lactate dehydrogenase (LDH), which enters the TCA cycle, and increases ATP production in the neurons via oxidative phosphorylation (Fig. 8.1). This view is highly discussed, pro [4, 5]) and contra [1, 6]. 

A modeling approach was used to determine which mechanisms are appropriate to explain typical brain lactate kinetics observed upon activation [7]. The model takes into account the mechanisms that are known to determine extracellular lactate concentration and includes a systematic study of the effects of changing parameters, such as the effect of cellular production or consumption of lactate, regional 

There are virtually no data whether neurons use ambient glucose, and/or glial-derived lactate under neoropathological conditions. It has been proposed that glycolytic enzymes such as phosphofructokinase (PFK), and glyceraldehyde-3- 

Disease Diseased proteins Major affected region Pathology 

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Table 8.2 Involvement of glycolytic enzymes in impairing the energy metabolism of conformational diseases.

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