|Questions About Lectins|
Lectin-Scrubbing with Deflect
I have difficulty losing weight and was interested in perhaps taking Deflect to "scrub" my body clean of all those nasty lectins adhering to my insulin receptor sites (they are probably all wheat lectins). Anyway, I read your article on Deflect, describing how it contains sacrificial carbohydrates to which lectins attach. My question is this....how do you know that a lectin happily sitting on a fat cell's insulin receptor site will want to move to a sacrificial carbohydrate? Why would it prefer the sacrificial carbohydrate over my fat cell?
To understand the answer to this question we should understand the nature of lectin binding. Lectins bind to carbohydrates reversibly or irreversibly. This is dependant on the shape characteristics of both the sugar that they are specific for and nature of the amino acid residues to which the sugar is linked to the cells wall. Small changes in the structure of the sites, such as the substitution of only one or two amino acids, also result in marked changes in specificity and avidity (the degree, or force of the attraction). Thus, although the sugar is the point of specificity, the amino acid 'stalk' determines much of the particular binding characteristics. (1) Some evidence also indicates that coordination with metal ions may occasionally play a role too.
The sugar is linked to the lectin mainly through charge attraction via covalent (electron sharing) bonds. The individual electron within these clouds of electrons are always moving.
Sometimes the one area of the cloud is more dense than another. This leads to the formation of a transient dipole within the molecule. The transient dipole can induce a dipole in an nearby molecule, by attracting its electrons. The attraction between the two oppositely oriented dipoles is termed a van der Walls interaction. In essence, van der Walls forces tend to 'push' the molecules towards each other, while shape conformity tends to 'pull' them towards each other.
Thus the attraction between lectins and carbohydrates is determined by both shape and charge.
One factor which influences agglutination is the zeta potential which surrounds the negatively-charged surface of the cell. Almost all particles in contact with a liquid acquire an electronic charge on their surfaces. Because of the large amount of sialic acids on the cell membrane the zeta potential is a bit more neutral compared to the charge on particles in suspension which are a bit more negatively charged. Most lectins are very highly positively charged.(3) Thus two amino sugars of similar shape can have two different levels of lectin avidity due to differences in their relative charge.
If we add to this slight structural differences in the amino acid residues between carbohydrates embedded in the cell membrane matrix and free carbohydrate in suspension, we get the force difference necessary to overcome the rather weak covalent bonds and van der Walls forces.
Just how 'hot' is this concept? Here's a summary from a just-published article:
"It is thus justified to compare crucial carbohydrate epitopes with the postal code ensuring correct mail routing and delivery. In view of the functional relevance of lectins the design of high-affinity reagents to occupy their carbohydrate recognition domains offers the perspective for an attractive source of new drugs. Their applications can be supposed to encompass the use as cell-type-selective determinant for targeted drug delivery and as blocking devices in anti-adhesion therapy during infections and inflammatory disease." (2)
Although completely unrelated, two other reasons amino sugars can be of use in weight management therapies:
1. They bind dietary fat. (4)
2. They increase production of the 'anti-fat' hormone, leptin (5) Leptin* acts on receptors in the hypothalamus of the brain where it inhibits food intake counteracts the effects of neuropeptide Y (a potent feeding stimulant secreted by cells in the gut and in the hypothalamus).
1. Sharon N, Lis H. Related Articles Lectins--proteins with a sweet tooth: functions in cell recognition. Essays Biochem. 1995;30:59-75. Review.
2. Rudiger H, Siebert HC, Solis D, Jimenez-Barbero J, Romero A, von der Lieth CW, Diaz-Marino T, Gabius HJ. Medicinal chemistry based on the sugar code: fundamentals of lectinology and experimental strategies with lectins as targets. Curr Med Chem. 2000 Apr;7(4):389-416. Review.
3. Monsigny M, Roche AC, Sene C, Maget-Dana R, Delmotte F. Sugar-lectin interactions: how does wheat-germ agglutinin bind sialoglycoconjugates? Eur J Biochem 1980 Feb;104(1):147-53
4. Han LK, Kimura Y, Okuda H. Reduction in fat storage during chitin-chitosan treatment in mice fed a high-fat diet.Int J Obes Relat Metab Disord 1999 Feb;23(2):174-9
5. McClain DA, Alexander T, Cooksey RC, Considine RV. Hexosamines stimulate leptin production in transgenic mice. Endocrinology 2000 Jun;141(6):1999-2002
* Not lectin!