Lipid A, the lipid component of bacterial lipopolysaccharides: relation of chemical structure to biological activity.
Lipopolysaccharides are integral components of the outer membrane of Gram-negative bacteria and they participate in various membrane functions essential for bacterial growth and survival. Lipopolysaccharides also represent the endotoxins of Gram-negative bacteria and possibly play a role for the pathogenesis and manifestations of bacterial infections. These biological activities are mediated mainly by the lipid component of lipopolysaccharides, termed lipid A. Chemically, lipid A consists of a beta 1, 6-linked D-glucosamine disaccharide which carries substituted phosphoryl groups and a range of D-3-hydroxy and D-3-acyloxyacyl residues, the latter being arranged in a hexagonal dense packing. A number of experimental data allow the conclusion that the highly ordered and compact lipid A structure confers stability to the outer membrane, renders it less permeable to lipophilic molecules and by providing a proper fluidity stabilizes the conformation of biologically active membrane proteins. For endotoxic activities of lipid A the polar substituents of phosphate residues are dispensable. The presence of D-3-hydroxy (or acyloxy) acyl-groups, linked to the glucosamine disaccharide, however, seems to be of importance. Analyses of now available synthetic lipid A analogues are expected to allow a more precise characterization of substructures and conformations required for the expression of physiological functions and endotoxic activities of lipid A.
D055598:Chemical Phenomena; D002621:Chemistry; D008050:Lipid A / Q000032:analysis* / Q000633:toxicity; D008070:Lipopolysaccharides / Q000032:analysis*; D008958:Models, Molecular; D012475:Salmonella / Q000032:analysis*; D013045:Species Specificity
D008050:Lipid A; D008070:Lipopolysaccharides