Amidation Astrocytes

Fig. I. Simplified scheme of the TCA cycle and the formation of glutamate from a-ketoglutarate (a-kg). In astrocytes glutamate is amidated to glutamine in GABAergic neurons some of the glutamate is decarboxylated and enters the GABA shunt. In both neurons and astrocytes anaplerosis occurs via carboxylation of pyruvate to malate or oxaloacetate (ox-ac) from which aspartate is formed.

Fig. 2. Metabolic interactions between neurons and astrocytes. Glucose enters the brain through the astrocytic end feet that envelop brain capillaries. In the astrocytes some of the glucose is metabolized to lactate which is exported to the extracellular fluid and taken up by neurons. In neurons lactate is converted to pyruvate which is either decarboxyiated to acetyl-CoA or carboxykited to malate to enter the TCA cycle. Glutamate may therefore be formed in neurons from a-ketoglutarate or from glutamine, which is imported from astrocytes. The glutamate that is released is taken up by astrocytes and amidated to glutamine or metabolized via the TCA cycle. The malate thus formed may leave the TCA cycle and become decarboxyiated to pyruvate and lactate. For lack of space, astrocytic pyruvate carboxylation is indicated only by the reversible formation of lactate. Notice that the relative importance of the various pathways in vivo is a matter of debate (see text).

Primary cultures of neurons, but not astrocytes, contain detectable quantities of a lipid component which we have identified as NAPE by enzymatic cleavage, multiple chromatographic analyses and nuclear magnetic resonance spectroscopy. Neuronal NAPE is composed of a variety of molecular species, which differ in the fatty acyl group bound, through an amide bond, to the ethanolamine moiety of phosphatidylethanolamine (PE). We have found at least five such molecular species in cultured neurons (Table 6.1). 

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