**4. IEM**

98 Dehydrogenases

of the stored energy substrate glycogen to glucose and further lactate production for shuttling to the neurons. This concept of ALNS shuttle during activation has received opposition and few groups suggest that lactate is primarily produced by the neurons and is

**Figure 4.** Schematic of neuroenergetics pathways: The astrocyte – neuron lactate shuttle.

pathway of glucose in the generation of lactate.

In summary whether lactate flux moves from astrocytes to neurons or vice-versa the important point is that glucose is not the sole substrate utilized in the brain. Lactate plays an equally important role especially during activation, neurotransmission and pathological conditions such as under ischemic insults. This further emphasizes the still dismissed importance of lactate dehydrogenase which represents the key switch in the metabolic

then transported from the neurons to the astrocytes (38;40).

Mutation in single gene leads to enzyme deficiency that results in type of genetic disorders termed as inborn error in metabolism (IEM) (46-50). IEM related deficiencies are generally autosomal recessive or X-linked. IEM linked enzyme deficiencies may be directly related to metabolic pathways of energy metabolism, purines/pyrimidine synthesis or degradation, amino acid synthesis, fatty acid oxidation, etc. Metabolic errors lead to accumulation of toxic or absence of essential products in the brain with neurological implications such as ataxiamotor control, encephalopathy, mental deficits, learning disabilities and mental retardation with structural anomalies. Some examples of DHOs involved include the pyruvate dehydrogenase complex.
