Arabinogalactan is a biopolymer consisting of arabinose and galactose monosaccharides. Two classes of arabinogalactans are found in nature: plant arabinogalactan and microbial arabinogalactan. In plants, it is a major component of many gums, including gum arabic and gum ghatti. It is often found attached to proteins, and the resulting arabinogalactan protein (AGP) functions as both an intercellular signaling molecule and a glue to seal plant wounds.
The microbial arabinogalactan is a major structural component of the mycobacterial cell wall. Both the arabinose and galactose exist solely in the furanose configuration. The galactan portion of microbial arabinogalactan is linear, consisting of approximately 30 units with alternating β-(1-5) and β-(1-6) glycosidic linkages. The arabinan chain, which consists of about 30 residues, is attached at three branch points within the galactan chain, believed to be at residues 8, 10 and 12. The arabinan portion of the polymer is a complex branched structure, usually capped with mycolic acids; the arabinan glycosidic linkages are α-(1-3), α-(1-5), and β-(1-2).
Structure of microbial arabinogalactan
The reducing end of micobacterial arabinogalactan consists of the terminal sequence →5)-D-Galf-(1→4)-L-Rhap-(1→3)-D-GlcNAc. A muramyl-6-P is also found within the peptidoglycan functional group. The mycolylarabinogalactan of mycobacteria is attached to the peptidoglycan by the actinomycete-specific diglycosylphosphoryl bridge, L-Rhap-(1→3)-D-GlcNAc-(1→P).
Arabinogalactan contains a galactan chain, with alternating 5-linked β-D-galactofuranosyl (Galf) and 6-linked β-D-Galf residues. The arabinan chains are attached to C-5 of some of the 6-linked Galf residues. There are three major structural domains for arabinan. The first is a domain consisting of linear 5-linked α-D-Araf residues. The second is a domain with branched 3,5 linked α-D-Araf residues substituted with 5-linked α-D-Araf units at both branched positions, and the third is A terminal non-reducing domain for end arabinan consisting of a 3,5-linked α-D-Araf residue substituted at both branched positions with the disaccharide β-D Araf-(1→2)- α-D-Araf. These three arabinan chains are attached to the galactan at residues 8, 10, and 12.
The non-reducing end of arabinogalactan is covalently attached to the mycolic acids of the outer membrane. The hydrophobicity of mycolic acids is a barrier to drug entry. Additionally, the mycolyl arabinogalactan peptidoglycan is responsible for aspects of disease pathogenesis and much of the antibody response in infections. The mycolyl substituents are selectively and equally distributed on the 5-hydroxyl functions of terminal- and the penultimate 2-linked Araf residues. The mycolyl residues are clustered in groups of four on the non reducing terminal pentaarabinosyl unit (β-Araf-(1→2)-α-Araf)2-3,5-α-Araf . Thus, the majority (66%) of the pentaarabinosyl units are substituted by mycolic acids, leaving the minority (33%) available for interaction with the immune system.
Approximately one of the three arabinosyl chains attached to the galactan chain contains succinyl groups. Although one succinyl group is most common, up to three succinyl groups per released arabinan fragment can be found on oligo-arabinans. However, arabinan fragments substituted with GalNH2 are not succinylated. Importantly, in the case of M. tuberculosis, and most likely in all slow growing organisms, both positive charge (protonated GalNH2 as GalNH3+) and negative charge (succinyl) are present in the middle regions of the arabinan, specifically at O-2 of the inner 3,5-α-D-Araf units. The succinyl residues are on the non-mycolylated chain. Recently, a complete primary model of arabinogalactan has been proposed.
Arabinogalactan from Western and Eastern larch tree is self-affirmed as GRAS for use in nutritional supplements. This affirmation is based on a report of a panel of experts qualified to evaluate the safety of substances added to food. It also meets the pre-1994 requirements of the Dietary Supplement and Health Education Act (DSHEA), indicating that it may be sold in the United States as a dietary supplement.
Extensive research has been conducted on larch Arabinogalactan since 1970 including three articles in the SCIENCE NEWS, trade magazine of the research industry in 1971. Studies at Washington State University (1972), University of Montana, University of Minnesota Agricultural Experimental Station at Crookston, University of Minnesota (1998-99) and Purdue University. Larch Arabinogalactan was approved by the FDA in 1972 for direct addition to food and with GRAS status in 1998.
Arabinogalactan has a strong safety profile. The safety of Arabinogalactan is supported by its daily consumption in common fruits and vegetables, its fermentation by bacteria in the human colon and its ability to rapidly signal fecal bacteria enzymes to begin the fermentation process.
Joint FAO/WHO Expert Committee on Food Additives (JECFA) included Arabinogalactan into section “Jellifying Agents, Thickening Agents, Stabilizers of Botanical Origin” and registered it under number E-409. Arabinogalactan from the Western and Eastern larch tree is currently approved in Australia, New Zealand, Canada, Europe, Japan, South Korea, Taiwan, and Thailand.
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