Lipid A is a kind of glycerophospholipid with the characteristics of hydrophilicity and hydrophobicity. It is composed of glucosamine, fatty acid, and pyrophosphate. Its skeleton is composed of two glucosamine β- The 1,6 positions are polymerized by pyrophosphate bonds and are hydrophilic. A variety of long-chain fatty acids and pyrophosphates are linked to the disaccharide chain by lipid bonds and amide bonds respectively. The structure of long-chain fatty acids can make lipid A hydrophobic. Lipid A is the main bioactive component of endotoxin. The chemical structure of lipid A of various gram-negative bacteria is very similar. Although there may be differences between them, there is no species specificity. The chemical structure of lipid A is shown in the figure.

In lipid A molecule, fatty acids account for about 70%~80%. The fatty acid properties and arrangement of various bacteria are different. Intestinal bacteria contain hydroxylated fatty acids, especially hydroxylated myristic acid（ β- Hydroxymyristic acid) is its specific component, while other bacteria do not have hydroxylated myristic acid or other hydroxylated fatty acids. Anaerobic melanoid bacilli have unique fatty acids, which can be cyclic or odd carbon chain fatty acids, lacking β- Hydroxylated myristic acid. Lipid A is insoluble in water but soluble in phenol, gasoline, pyridine, triethylamine, dimethyl sulfoxide, and sodium hydroxide.

In 1960, Westphal et al. first reported that lipid A was the biologically active component of endotoxin, and then Otto L ü ideritz et al. confirmed the activity of lipid A by two methods. One method was to change the chemical structure of KDO residue in the lipopolysaccharide of the polysaccharide-deficient mutant, and the activity of lipopolysaccharide (lethality, pyrogenicity, anti-complement activity of mice and chicken embryos) remained unchanged, indicating that the toxicity was not in lipopolysaccharide, but in lipid A; The other method is to separate and extract the inactivated bacteria, and combine the insoluble lipid A obtained with water-soluble carriers such as albumin to form stable soluble lipid A, and determine its activity directly. The experiment confirmed that lipid A has lethal, febrile, anti-complement activity, bone marrow necrosis, positive lysate test of limulus lysate, and other biological activities in mice.

Although the activity of lipid A is slightly lower than that of the crude lipopolysaccharide, it can still indicate that the active site of lipopolysaccharide is lipid A. However, the presence of polysaccharides helps insoluble lipid A to dissolve easily and play its role. The toxicity of lipid A mainly lies in its fatty acid linked by lipid bonds. If the latter is hydrolyzed by lysosomal enzymes in neutrophils and macrophages, such as AOAH, and becomes deacylated lipid A, resulting in changes in its spatial structure, the lipid A or lipopolysaccharide will lose its toxicity. Although the chemical composition and structure of lipid A of various gram-negative bacteria are different, they are very similar to each other, which explains that the activity of endotoxin, including the reaction to the human body, is basically the same, but it is not excluded that in different species, such as humans and mice, the reaction to some endotoxins is opposite.

Lipid A is the most conservative part of LPS. It is also a common component in the molecular structure of lipopolysaccharide of gram-negative strains. It is currently considered as the pathogen-associated molecular pattern (PAMP) of GNB, which is recognized by the host's natural immune system: such as TLR, CD14, and other receptors that recognize PAMP molecules. It was found that the structural integrity of lipid A (such as phosphatidyl lipid A) was related to the toxicity of LPS, while monophosphoryl lipid A or monophosphoryl lipid A precursors (such as lipid x, lipid Y) could not cause fever, local Shwartzman reaction or fatal shock. Therefore, some people have studied the study and treatment of using the precursor of monomer lipid A to induce the body's tolerance to endotoxin. At present, it is believed that lipid A and KDO are the most toxic components in LPS structure, and do not need О Most of the specific chains and core polysaccharides, such as Bg-LPS, are involved because they lack the KDO and β Hydroxylated myristic acid, the activity of endotoxin is relatively weak. Lipid A and KDO also have immunogenicity, which can activate the body's immune system and cause the body to produce corresponding antibodies.

There are two lipid forms of endotoxin extracted by general methods, namely lipid A and lipid B. Lipid B is weakly combined with other components of endotoxin, and can be extracted by general lipid solvent. It may belong to cephalin and has no biological activity. Since the removal of lipid B has no effect on the activity of endotoxin, lipid B is not the true toxic component of endotoxin. Lipid A combines with polysaccharides to form lipopolysaccharide.

The typical lipopolysaccharide molecule is composed of the above three parts, but in some gram-negative bacteria (such as Haemophilus, Neisseria, etc.), only a few sugar groups have replaced О The specific polysaccharide chain is connected to the outer part of the core polysaccharide, so this kind of lipopolysaccharide is usually called lipopolysaccharide (LOS).