Chemistry Reference
In-Depth Information
30.1
Glucose and Glycogen as Energy Sources
Glucose is both the primary energy source for neural cells and a major building
block for a number of CNS and PNS glycoconjugates. Glucose enters the brain by
means of the Glut-1 transporter in endothelial cells that comprise the blood-brain
barrier. Unlike many other cells that convert glucose into glycogen as an energy
reserve, neurons do not catalyze this reaction under normal conditions even
though they possess the glycogen synthase enzyme. Paradoxically, failure to keep
this enzyme silent results in glycogen synthesis with concomitant damage to
neurons by apoptotic signaling [1]. Neurons nevertheless depend on glycogen
indirectly through metabolism of this polysaccharide by astrocytes, its primary
locus. These cells carry out active glycogenolysis with release of lactate that is uti-
lized, along with glucose itself, as a major energy substrate by neurons. Glucose
also modifi es neural cell activities in several ways independent of energy provision,
for example glycosaminoglycan (GAG) production, insulin signaling, c-Jun
N - terminal kinase/mitogen - activated protein kinase activation and UDP - GlcNAc
formation - the substrate for an important posttranslational modifi cation (see
below).
30.2
Gangliosides as Primary Glycans of the Nervous System
Gangliosides are defi ned as GSLs containing at least one sialic acid in the oligosac-
charide chain; the vast majority possess glucose as the fi rst carbohydrate attached
to ceramide (Figure 30.2; please see also Chapter 10 for survey on glycolipids).
The fi rst identifi cation and structural characterization of specifi c gangliosides
resulted from the pioneering studies of Ernst Klenk and coworkers on lipid storage
diseases of brain during the 1930s and 1940s [2]. Klenk assigned the term ' gan-
glioside' in relation to their special abundance in brain gray matter, known to be
the primary locus of neurons or 'Ganglionzellen'. It was later recognized, however,
that gangliosides are not unique to neurons and occur, albeit at lower concentra-
tions, in all neural cell types and indeed in virtually all vertebrate (and even some
invertebrate) tissues. The nervous system is unique among mammalian tissues in
possessing gangliosides (rather than glycoproteins) as the predominant sialogly-
coconjugates (for the different forms of glycoprotein sialylation, please see Chap-
ters 6 and 7); gangliosides represent around 75% of total bound sialic acid. Neurons
contain the highest concentration - the majority of these belonging to the ganglio-
tetraose family characterized by a four-carbohydrate backbone structure to which
one or more sialic acids are attached (Figure 30.2 and also Chapter 10.7 ). Ganglio-
sides, as with GSLs in general, are named and classifi ed according to the oligosac-
charide structure, irrespective of the frequent heterogeneity in the lipophilic
components of ceramide. A recent review [3] has listed 188 different gangliosides
that have been characterized in vertebrate tissues to date, of which perhaps about
