Polysaccarides / Glycoproteins

The cell walls of mushrooms differ significantly from those of vascular plantsin their structure and composition. This fact clearly substantiates the special status fungi occupy in the ecosystem. The fungal cell wall consists mostly of glycoproteins embedded in the cell membrane, of chitin (ß 1.4-linked unit of acetyl glucosamine) and the branched ß 1.3/ß 1.6 glycans. However, concentration of individual components can vary significantly: 1 - 20 percent of chitin, 50 percent of ß-glycan and 20 - 40 percent of glycoproteins. Most of the glycoproteins are embedded in the cell membrane through linkages.

Apart from these structural proteins, which are covalently joined to the ß 1.3/ß 1.6 glycans through their carbohydrate side chains, the cell walls also accommodate enzymes (chitinases, glycanases, peptidases) that are important for the restructuring required during fungal development. Usually, these enzymes are also glycoproteins that can be covalently joined to ß-glycans.

Definition

Polysaccharides - also known as glycans - are multiple sugars (polyose) and a carbohydrate sub-category. Their names vary depending on the individual sugars of which they are composed. These eight essential sugars are the polysaccharide building blocks: glucose, galactose, mannose, fucose, xylose, N-acetylglucosamine, N-acetylgalactosamin, N-acetylneuraminic acid.

One subset, the proteoglycans (mucopolysaccharides), is an essential component of the extra-cellular matrix and the cell surface. Proteoglycans can absorb large amounts of water. They are characterised by a high polysaccharide content of 80 to 94 percent at a low protein content of six to 20 percent. Protein-bound glycans -i.e. glycoproteins that are particularly found in powder derived from whole mushrooms - act more effectively on the immune system than pure polysaccharides do.

Today, research is focused on ß-1-3- and ß-1-6 glycans, the main types found in the mushrooms. These are glucose-based polysaccharides with a special chemical structure that is of particular importance for our immune system. They have special names depending on the mushroom they are found in: lentinan from Shiitake (Lentinula edodes), pleuran from Pleurotus ostreatus, grifolan or D-fraction from Maitake (Grifola frondosa).

Incidence

Examples of polysaccharides are, e.g. glycogen (stored sugar in human beings, animals and pillar fungi), starch (stored sugar in plants), cellulose and chitin. They all serve as important reserve substances and basic nutritional sources.

ß-glycans are found in algae, oats, wheat and yeast - but the greatest variety is found in mushrooms. Besides the well-studied ß-glycans, mushrooms contain numerous other biologically active polysaccharides. Plants mainly contain less effective ß-1.4-glycans that have a molecular weight of 45,000 to 50,000 Dalton while fungal ß-glycans weigh from 1.5 to 2 million Dalton. It is speculated that a high molecular weight has more beneficial and complex effects on our body. Moreover, the fungal fruiting body has been found to contain a higher overall amount and larger variety of polysaccharides and glycoproteins than the mycelium. The concentration depends on the fruiting body stage of development, and the polysaccharide activity increases with advancing fruiting body development and growth. Consequently, only mature fruiting bodies should be used for mushroom powder.

Properties

Polysaccharides feature the highest potential to change their chemical structure and thus have the greatest and best capacity to communicate biological information. This enables an enormous flexibility, which is necessary to influence precise regulatory mechanisms in higher organisms. While, for instance, only 24 oligopeptide configurations can be derived from four peptides (proteins), more than 1,000 different oligosaccharide configurations can be derived from four carbohydrate molecules.

The detailed structures of numerous other fungal ß-glycans are still unclear. In order to be effective, it seems that ß-glycans need to have a ß-1.3- or ß-1.6 link. The more complex and branched they are, the more complex their effects on the human body seem to be.

A research study conducted by Rice found that the intestinal absorption of ß-glycans to be an active process that is dependent on the gastrointestinal macrophages - i.e. on a sound intestinal flora. Tagged ß-glycans have been found in the lymph nodes and the spleen three days after being consumed and in the bone marrow four days after being consumed. In all cases they were found in the macrophages.

Within the first three days of being orally consumed, ß-glycans do not cause any changes. They are decomposed between 14 and 21 days. The fragments resulting from this process are biologically active, released outwards and retained on the granulocytic membrane after only four days, where they unfold their stimulation of the the immune system.

The degree of polymerisation level, i.e. the ß glycan branching, determines the molecular weight and thus the human body’s capability of absorbing the sugar. Polysaccharides with a low molecular weight are soluble in alcohol but have little influence on our immune system.

Correlation between chemical structure and effectiveness

Japanese and Chinese scientists have studied some fungal polysaccharides and their glycoproteins through stages I, II and II of clinical research. However, their size and structural complexity make it difficult to study their functional mechanisms in detail. On the one hand, glycoproteins with a high molecular weight (800,000 to 1,500,000 Dalton) are reported to have a strong influence on numerous immune functions, but if their size is reduced by heating (extraction), the range and intensity of their effectiveness is proportionally diminished. In vitro-studies have shown that ß-glycans with a high molecular weight can directly activating leucocytes. According to Fadok et al., ß-glycans with a high molecular weight improve the macrophages’ ability to identify and eliminate apoptotic cells. Biological activities in vitro also been found for ß-glycans with low or medium molecular weight, but their effects on the cells are less clear. ß-glycans with very low molecular weight (5,000 to 10,000 Dalton) - as found in cereals - are inactive. Other studies have indicated that denaturation (extraction) reduces the monocytic activity induced by cytokines and that the isolation into individual substances substantially reduces their effectiveness.

Until it is clear which isolated polysaccharide is most effective, one should implement them in the form nature has provided them: naturally, non-denaturised and in the natural combination of their highly varied structures. This is also verified by several studies: Ghoneum et al., 1995; Wedam and Haynes, 1997 and Sawai et al., 2002 all show that a natural combination of different polysaccharides, ß-glycans and glycoproteins has comparatively stronger influence on the immune system.

Effects on the immune system

ß-glycans resemble the polysaccharide chains found on the outer cell wall of bacteria. This simulates intruding pathogens and trains the defence system. The human body does not synthesise ß-glycans, so that the immune system identifies them as foreign matter and stimulates our inherent and trained immune responses. In other words: ß-glycans have molecular properties resembling those of pathogens. They are thus identified by specific receptors on the cell surface and trigger an immune response.

The effect ß-glycans have on our inherent unspecific immune response is to increase the cytotoxicity and cytokine production of macrophages, natural killer cells and neutrophilic granulocytes. By producing free oxygen and nitrogen radicals (NO gas), they trigger a counteraction to degenerated cells, viruses and bacteria. The effect on our acquired immune response is the activation of dendritic cells. These are derived from monocytes and confront the T cells with antigens. Additionally, ß-glycans stimulate the production of the cytokines and chemokines IL-8, IL-1b, IL-6, and TNF-a as well as the macrophages’ ability to identify and eliminate apoptotic cells.

In animal experiments and clinical studies ß-glycans have demonstrated antiviral effects against HIV (increase of CD4 cells), hepatitis B (stimulated phagocytosis) and the swine flu virus (reduction of viral nucleic acids in infected animal cells, increase of interferon-gamma and NO gas), and antibacterial and antifungal properties. Wound healing is also promoted through the increased macrophage activity.

Moreover, a direct cytotoxic effect on cancer cells by polysaccharides has been found. ß-glycans can thus inhibit the onset of cancer and the spread of tumours. Furthermore, active polysaccharides are roughage that absorb potential carcinogens and promote their excretion via the intestines.

Other effects of polysaccharides

They lower the cholesterol level, although this mechanism has not yet been precisely clarified. One theory contests that they account for an increased release of bile acids, so that more cholesterol is excreted. According to another theory, the production of cholesterol in the liver is better regulated.

ß-glycans also reduce the level to which the blood sugar rises after meals. The exact functional principle is also still not fully understood. Most likely, the fungal chitin is able to absorb the broken down sugar in the intestines, so that more sugar is excreted unconsumed. Furthermore, the direct increase of the insulin value is under consideration. ß-glycans also have triglyceride-lowering properties and are very helpful diabetic arteriosclerosis. This would also explain their blood sugar level and blood pressure regulating effect.

Sources

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