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Antinutritive effects of wheat-germ agglutinin and other N-acetylglucosamine-specific lectins

Br J Nutr 1993 Jul;70(1):313-321 Pusztai A, Ewen SW, Grant G, Brown DS, Stewart JC, Peumans WJ, Van Damme EJ, Bardocz S Rowett Research Institute, Bucksburn, Aberdeen.

Incorporation of N-acetylglucosamine-specific agglutinins from wheat germ (Triticum aestivum; WGA), thorn apple (Datura stramonium) or nettle (Urtica dioica) rhizomes in the diet at the level of 7 g/kg reduced the apparent digestibility and utilization of dietary proteins and the growth of rats, with WGA being the most damaging. As a result of their binding and endocytosis by the epithelial cells of the small intestine, all three lectins were growth factors for the gut and interfered with its metabolism and function to varying degrees. WGA was particularly effective; it induced extensive polyamine-dependent hyperplastic and hypertrophic growth of the small bowel by increasing its content of proteins, RNA and DNA. Furthermore, an appreciable portion of the endocytosed WGA was transported across the gut wall into the systemic circulation, where it was deposited in the walls of the blood and lymphatic vessels. WGA also induced the hypertrophic growth of the pancreas and caused thymus atrophy. Although the transfer of the gene of WGA into crop plants has been advocated to increase their insect resistance, as the presence of this lectin in the diet may harm higher animals at the concentrations required to be effective against most pests, its use in plants as natural insecticide is not without health risks for man.

Lectins and also bacteria modify the glycosylation of gut surface receptors in the rat

Glycoconj J 1995 Feb;12(1):22-35 Pusztai A, Ewen SW, Grant G, Peumans WJ, Van Damme EJ, Coates ME, Bardocz S

Rowett Research Institute, Bucksburn, Aberdeen, UK.

Oral exposure to lectins or the presence or absence of bacteria in the small intestine were shown by histological methods using anti-lectin antibodies or digoxigenin-labelled lectins to have major effects on the state of glycosylation of lumenal membranes and cytoplasmic glycoconjugates of epithelial cells. Taken together with the dramatic effects of exposure to lectins on gut function, metabolism and bacterial ecology, this can be used as a basis for new perspectives of biomedical manipulations to improve health.

Relationship between survival and binding of plant lectins during small intestinal passage and their effectiveness as growth factors

Digestion 1990;46 Suppl 2:308-316 Pusztai A, Ewen SW, Grant G, Peumans WJ, van Damme EJ, Rubio L, Bardocz S

Rowett Research Institute, Bucksburn, Aberdeen, Scotland, UK.

  • The effects on the small intestine and the growth of rats of six pure plant lectins: PHA (Phaseolus vulgaris); SBL (Glycine maxima); SNA-I and SNA-II (Sambucus nigra); GNA (Galanthus nivalis) and VFL (Vicia faba), covering most sugar specificities found in nature, were studied in vivo. Variable amounts, 25% (VFL) to 100% (PHA, GNA) of the lectins administered intragastrically, remained in immunochemically intact form in the small intestine after 1 h. All lectins, except GNA, showed binding to the brush border on first exposure, although this was slight with VFL. Thus, binding to the gut wall was not obligatory for resistance to proteolysis. Exposure of rats to lectins, except VFL, for 10 days, retarded their growth but induced hyperplastic growth of their small intestine. The two activities were directly related. PHA and SNA-II, whose intestinal binding and endocytosis was appreciable after 10 days of feeding the rats with diets containing these lectins and similar to that found on acute (1 h) exposure, were powerful growth factors for the small intestine.
Toxicity of kidney bean (Phaseolus vulgaris) in rats: changes in intestinal permeability

Digestion 1985;32(1):42-46

Greer F, Pusztai A

  • Rats fed on diets containing kidney bean showed increased intestinal permeability to intravenously injected 125I-labelled rat serum proteins after an intragastric challenge with bean proteins. The enhanced accumulation of radioactive serum proteins in the lumen and walls of the small intestine indicated increased vascular permeability. It is suggested that dietary lectins may, at least in part, be responsible for this loss of serum proteins and thus contribute towards the overall toxicity of kidney bean proteins.
Effect of kidney bean (Phaseolus vulgaris) toxin on tissue weight and composition and some metabolic functions of rats

Br J Nutr 1985 Jul;54(1):95-103

Greer F, Brewer AC, Pusztai A

  • Inclusion of kidney bean (Phaseolus vulgaris) proteins in the diet for rats was shown to affect the weight of some internal organs. Of these, in addition to the well-known hypertrophy of the pancreas attributable to dietary trypsin inhibitors, the observed atrophy of the thymus and the doubling in weight of the small intestine are related to the protein or lectin content of the bean diet, or both. Changes in tissue composition of the small intestine were also recorded. Its protein content increased by about 40-50% and carbohydrate content doubled suggesting the occurrence of increased mucinous glycoprotein secretion. Increased DNA content (by about 30-40%) however also indicated mucosal hyperplasia. The results gave further support to previous suggestions that the oral toxicity of kidney-bean lectins involves local reactions in the small intestine in combination with their effects on the systemic immune system and general metabolism.
The nutritional toxicity of Phaseolus vulgaris lectins

Proc Nutr Soc 1979 May 1;38(1):115-120 Pusztai A, Clarke EM, King TP

In rats fed on beans (Phaseolus vulgaris) the poorly digestible lectins were shown to react with intestinal cells in vivo and to cause a disruption of many of the brush borders of duodenal and jejunal enterocytes. Although depressed to a certain extent, absorption still occurred, probably through the non-disrupted cells of the small intestine. In addition, abnormal absorption of potentially harmful substances, lectin-related or of bacterial origin, could also occur, possibly as a direct effect of the disruption caused by the lectins on the enterocytes. It is suggested that toxicity was the result of ensuing systemic effects, such as for example the observed high N excretion possibly through increased tissue catabolism.

Effect of phytohaemagglutinin on intestinal cell proliferation. Role of polyamines

Arch Latinoam Nutr 1996 Dec;44(4 Suppl 1):16S-20S Bardocz S, Rowett Research Institute, Aberdeen, Scotland, UK.

The polyamines, putrescine, spermidine and spermine, mediate the effects of hormones and growth factors as second messengers. They are necessary for every step of protein, RNA and DNA synthesis and are therefore essential for cell growth and proliferation. As with hormones and peptide growth factors, plant lectins which bind to cell surface receptors of the brush border membrane are powerful extraneous growth factors for the gut and as a result, by interacting with brush border epithelial receptors, induce extensive proliferation and changes in the metabolism of epithelial cells via activation of second messenger pathways.These metabolic changes require vast amounts of polyamines, mostly spermidine. Thus, one of the first effects of the PHA signal is to stimulate the basolateral polyamine uptake system for the sequestration of polyamines from blood circulation in sufficient amounts to sustain the growth of the tissue.