Adhesion Molecules-28

Aging-9

Agricultural Biotechnology-37

Angiogenesis-29

Antisense-4

Apoptosis-49

Atherosclerosis-12

Autoimmunity-69

Bacterial Virulence-18

Bioinformatics-13

BioMaterials-18

Biosurfactants-1

Biotechnology-99

Cancer Genetics-25

Cancer Metastasis-19

Cell Biology-16

Cell Cycle-34

Cell Metabolism-327

Channels and Transporters-79

Chaperones-11

Circadian Rhythms-13

Coagulation-14

Cytokines/Growth Factors-52

Development-223

DNA-56

DNA Surveillance and Repair-42

Drug Design-17

Endocrine-66

Evolution-33

Extracellular Matrix-30

Gastroenterology-52

Gene Expression-178

Gene Therapy-53

Heart-61

Heat Shock Proteins-19

Hematology-11

Immunology-93

Infectious Disease-71

Ischemia-Reperfusion-33

Leptin and Leptin Antagonists-1

Medical-12

MHC-17

Mitochondria-17

Molecular Biology-11

Molecular Complexes and Signaling-1

Nanomedicine-30

Neurodegenerative Disease-72

Neuropharmacology-112

Neuroscience-38

Nucleus-15

Oncogenes-8

Oncology-87

Parasitic Disease-12

Pharmacogenomics-14

Prebiotic Evolution-2

Protein-12

Reproductive Biology-59

RNA-152

Signal Transduction-186

Stem Cells-80

Surgery-37

T-Cell Activation-12

Tissue Engineering-116

Transplant-51

Vaccines-82

Viruses-85

Chapter category: Oncology

Structure and Synthesis of Lipid A

Chapter authors:
Shoichi Kusumoto, Masahito Hashimoto and Kazuyoshi Kawahara

Lipid A is the lipophilic partial structure of bacterial lipopolysaccharide (LPS), which is a characteristic and essential component of the cell surface architecture of Gram negative bacteria. LPS constitutes the outer leaflet of the lipid bilayer of outer membrane which covers the outermost surface of bacterial cells. Structurally, LPS is composed of covalently bound three distinct parts, i.e., O‑antigenic polysaccharide, core oligosaccharide and glycolipid called lipid A (Fig. 1). Westphal and Lüderitz found that the linkage between the core oligosaccharide and glycolipid is selectively cleaved by mild acid hydrolysis of LPS. They also observed that the liberated glycolipid, which they named lipid A, is responsible for the endotoxic activity of LPS.1\r\nThe discovery of lipid A was a real epoch in the history of the human’s efforts towards the identification of the endotoxic principle which causes serious clinical problems during Gram‑negative infections.2 Even after that, however, further progress of structural study of lipid A was not straightforward because of the amphiphilic nature and intrinsic heterogeneity of this group of complex glycolipids. Lipid A has a strong tendency to aggregate, which inhibited isolation of homogeneous single molecular species to be subjected to the precise structural studies. The early structural studies were, therefore, carried out with heterogeneous mixtures of congeners often containing other cell components and even artifacts formed by partial degradations during isolation procedures. Nevertheless, the correct basic structure of enterobacterial lipid A was elucidated as follows.3,4 These lipid A share the common hydrophilic backbone consisting of a β(1‑6)‑linked disaccharide of 2‑amino‑2‑deoxy‑D‑glucose (D‑glucosamine, GlcN) 1,4\'‑bisphosphate which is acylated at two amino and several hydroxy groups. The major fatty acids linked to the backbone are hydroxylated at their 3‑ (or β‑)positions in R‑configurations, while certain proportion of nonhydroxylated normal fatty acids are always present. Because of its strong aggregation, however, the correct molecular weight of lipid A was not available. So that the possibility was not excluded of a macromolecular structure formed by phosphodiesters linking the backbone disaccharide units.\r\n

Shoichi Kusumoto
Suntory Institute for Bioorganic Research, Osaka, Japan.

Masahito Hashimoto

Kazuyoshi Kawahara

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