Chemistry Reference
In-Depth Information
30
Neurobiology Meets Glycosciences
Robert W. Ledeen and Gusheng Wu
The initial encounter of neurobiology with glycosciences appears to have occurred
in the nineteenth century, at roughly the same period in which lectinology had
its beginning (for a survey of history of lectinology, please see Chapter 15). Much
of the credit for those auspicious beginnings belongs to J.L.W. Thudichum,
considered by many the father of neurochemistry, who was a physician/scientist
of widely diverse talents. He became known among his peers as 'The chemist
of the brain' for his pioneering achievements including isolation and chemical
analysis of biomolecules from human and animal brain. For this he put to good
use the combustion apparatus given him by his teacher and renowned analytical
chemist Justus von Liebig. Limited to relying on solvent extraction, crystallization
and hydrolytic procedures, Thudichum accomplished the remarkable feat of iso-
lating in relative purity a number of brain lipids. These included cerebroside
and its close relative, sulfatide - the fi rst glycoconjugates to be characterized in
brain (or possibly any tissue). He showed cerebroside (galactosylceramide) to
consist of a long-chain base with a primary hydroxyl attached to a six-carbon
sugar, which he liberated by acid hydrolysis and termed ' cerebrose ' ; this later
acquired its present name, galactose. This galacto-form of cerebroside (Figure
30.1) is especially rich in the nervous system owing to its prominence in the
myelin sheaths encasing the larger axons. Thudichum's investigations were
carried out in a climate of intense controversy, his preparations being described
as 'impure smeary masses', the true nature of which no chemist would be able
to decipher (it was alleged). Prominent neuroscientists of his day, and even
somewhat later, spoke disparagingly of the chemical approach that produced
what was described as 'cerebral hash' from which little could be learned. Thu-
dichum's seminal contributions, which laid the groundwork for subsequent rev-
elations on the rich diversity of sphingolipids [including notably glycosphingolipids
(GSLs)] in the nervous system, became more fully appreciated following his death
in 1901. The Biochemical Society today awards a Thudichum Medal to those
who have made outstanding contributions to neurochemistry. Sphingosine
itself was fi rst isolated and analyzed by Thudichum who named it 'in
