Research and

Carbohydrate chain and lectins

The genetic code, that is three nucleotides (minimum unit of DNA) specify one amino acid, has been decoded, and the fundamental mechanism has also been elucidated that genetic information is first copied into the mRNA and then translated into protein via the ribosome and tRNA. The carbohydrate chain1 is also known as the third chain of life next to the gene and protein, playing an essential role in living organisms. However, little information is available on the specific roles of carbohydrate chains, and their roles have not been well elucidated compared with genes and proteins.2

As with the genetic code, the term glycocode may be used in the context of carbohydrate chains. However, the term suggests that information coded with carbohydrate chains remains largely unknown, not indicating that carbohydrate chains act as a blueprint like genes. Information that carbohydrate chains have is sent to other molecules through the following three major routes: (1) glycosylation-induced changes in protein conformation and interaction with other molecules, (2) interaction between carbohydrate chains, and (3) signal transduction through carbohydrate recognition by lectins. Among these, carbohydrate recognition by lectins is superior to other routes in specificity and intensity of interaction and is therefore believed to play a characteristic role in deciphering and transmitting carbohydrate chain information.

Although it is difficult to correctly define lectins, it may generally be defined as a protein that specifically recognizes and binds to carbohydrate chains or cross-links them (connects carbohydrate chains together).3 Carbohydrate chains have diverse information, and only lectin, which specifically recognize and bind to carbohydrate chains, can grasp linguistic and systemic information on the basis of their sugar sequence. As indicated by the definition, lectin is a generic name for various types of proteins that share a carbohydrate binding property, not a single family of proteins. Thus, the way in which lectins bind to carbohydrate chains and then transfer their information differs significantly depending on the type of lectin.

The largest group of animal lectins is called C-type lectins that require calcium ions for binding to carbohydrate chains. This group includes a variety of lectins, such as a secreted type (collectins and lecticans) and a membrane-integrated type (such as selectins). In addition to C-type lectins, various families of lectins are known, such as galectins, siglecs, L-type lectins, and I-type lectins. Galectins, a subject of our interest and research, was previously known as S-type lectins and were named from their property of binding to carbohydrate chains, particularly carbohydrates (ƒΐ-galactoside) containing galactose with high affinity (galactose + lectin ¨ galectin).

Note 1: Carbohydrate and carbohydrate chain: The term carbohydrate originally indicated a substance defined as a general formula of Cn(H2O)m, but now has a broader meaning. Carbohydrates include the most simple monosaccharides, oligosaccharides composed of 2 to 10 monosaccharides, and polysaccharides composed of more monosaccharides. Well known carbohydrates include monosaccharides of glucose and fructose and oligosaccharides of cane sugar (sucrose/saccharose, or table sugar) formed by the condensation of fructose and glucose. Glycogen stored in the muscle and liver in animals and cellulose in plants are produced by the condensation of many units of glucose (glycogen and cellulose differ in condensation process).
 Although carbohydrates, such as glucose and glycogen, are important especially as an energy source for living organisms, they do not carry such complicated information as DNA (genes). However, carbohydrates are known to have roles that are completely different from these. Proteins are chains of amino acids, and some proteins have carbohydrate chains attached to them (a protein with a carbohydrate chain is called a glycoprotein). The significance of carbohydrate chains was poorly known; however, recent studies have shed some light on their roles. In contrast to glycogen, carbohydrate chains of glycoproteins are formed by the condensation of many types of monosaccharides, and complicated information like genetic information may be coded in the monosaccharide sequence. Some lipids also have a carbohydrate chain (glycolipids).
Note 2: In contrast to genome research, researchers in Japan have been conducting extensive research on sugar and carbohydrate chains and have had a competitive edge over those in Europe and the United States. As a largely unexplored field in the post-genomic era, research projects targeting carbohydrate chains have been initiated or planned in Japan and other countries. This is a field where great progress is expected to be made mainly by Japanese researchers.
Note 3: Glycoforum web pages are useful as an information source for lectin and carbohydrate science.