Sugars - Biologically Relevant!

Title - Sugar Rush
New Scientist Vol 176 issue 2366 - 26/10/2002

Indeed, scientists are saying that glycomics could fuel a revolution in biology to rival that of the human genome. But it's not going to be easy. "If you ask, what is the glycome for a single cell type, it's probably many thousands of times more complex than the genome," says Ajit Varki, director of the Glycobiology Research and Training Center at the University of California, San Diego. "It's going to be a tough business."
Consider the complexity and subtlety of sugars, and it quickly becomes apparent that "tough" is, if anything, an understatement. For a start, the glycome's basic building blocks are far more numerous and varied than the four letters of the DNA alphabet or the score of amino acids that make proteins.
The complex sugar molecules that help make living things tick are all built up from simple sugars, or "monosaccharides" such as glucose, and about 10 others. Two ring-shaped monosaccharide molecules can link together to form a disaccharide, the other main building block of complex sugars. Things are made more complex because there are several different ways for the monosaccharides to link together, which leave the two units angled in different directions.
The problem only gets worse as monosaccharide and disaccharide units link together to form polysaccharides, the chains of sugars which in turn form the giant structures of complex sugars. These massive molecules, which can contain more than 200 units, not only come as long chains, but also as intricately branched structures that decorate the surfaces of cells like a forest of sugary filigree. It's the three-dimensional shape of these sugars that is key to their functions, such as cell recognition. And there's a further complication: different atoms or groups of atoms may be attached to the basic monosaccharide molecules, subtly changing their properties.
All of this adds up to a massive headache for scientists trying to understand the structures and functions of complex sugars. Do the maths and even a mere six-unit sugar of a kind called a glycosaminoglycan has a staggering 12 billion possible versions. Researchers still have no idea how many of all the possibilities are actually exploited by nature, says Ram Sasisekharan, a bioengineer who leads a multidisciplinary team at the Massachusetts Institute of Technology. "We're still scratching the surface in figuring out which sugars are biologically relevant," he notes.

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