WordNet

(botany) either of the two parts of a bilabiate corolla or calyx
either the outer margin or the inner margin of the aperture of a gastropods shell
either of two fleshy folds of tissue that surround the mouth and play a role in speaking
the 1st letter of the Roman alphabet (同)a
the blood group whose red cells carry the A antigen (同)type_A, group A
an oily organic compound insoluble in water but soluble in organic solvents; essential structural component of living cells (along with proteins and carbohydrates) (同)lipide, lipoid

PrepTutorEJDIC

〈C〉『くちびる』,口もと / 《複数形で》(発音器官としての)くちびる,口 / 〈U〉《俗》生意気な言葉 / 〈C〉(容器などの)口,へり,縁;(峡谷・火山などの)口 / 〈C〉(植物の)唇弁(しんべん)
answer / ampere
脂質,あぶら
arsenicの化学記号

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2014/07/13 22:50:34」(JST)

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Chemical structure of lipid A as found in E. Coli^[1]

Lipid A is a lipid component of an endotoxin held responsible for toxicity of Gram-negative bacteria. It is the innermost of the three regions of the lipopolysaccharide (LPS, also called endotoxin) molecule, and its hydrophobic nature allows it to anchor the LPS to the outer membrane.^[2] While its toxic effects can be damaging, the sensing of lipid A by the human immune system may also be critical for the onset of immune responses to Gram-negative infection, and for the subsequent successful fight against the infection.^[3]

Functions

Many of the immune activating abilities of LPS can be attributed to the lipid A unit. It is a very potent stimulant of the immune system, activating cells (for example, monocytes or macrophages) at picogram per milliliter quantities.

When present in the body at high concentrations during a Gram-negative bacterial infection, it may cause shock and death by an "out of control" excessive immune reaction.

Chemical composition

Lipid A consists of two glucosamine (carbohydrate/sugar) units with attached acyl chains ("fatty acids"), and normally containing one phosphate group on each carbohydrate.^[1]

The optimal immune activating lipid A structure is believed to contain 6 acyl chains. Four acyl chains are attached directly to the glucosamine sugars are beta hydroxy acyl chains usually between 10 and 16 carbons in length. Two additional acyl chains are often attached to the beta hydroxy group. E. coli lipid A, as an example, typically has four C14 hydroxy acyl chains attached to the sugars and one C14 and one C12 attached to the beta hydroxy groups.^[1]

The biosynthetic pathway for Lipid A in E. coli has been determined by the work of Christian R. H. Raetz in the past >32 years.^[2] Lipid A structure and effects on eukaryotic cells have been determined and examined, among others, by the groups of Otto Westphal, Chris Galanos, Ernst T. Rietschel and Hajime Takahashi starting already in the 1960s (Gmeiner, Luederitz,Westphal. Eur J Biochem 1969)(Kamio&Takahashi J Biochem 1971)(Luederitz, Galanos et al., J Infect Dis 1973).

Biosynthesis

Synthesis of the UDP-diacylglucosamine precursor of Lipid A ^[4]

Synthesis of Lipid IV_a^[4]

Inhibition and activation of immune response

Lipid A with a reduced number of acyl chains (for example; four) can serve as an inhibitor of immune activation induced by Gram-negative bacteria, and synthetic versions of these inhibitors are in clinical trials for the prevention of harmful effects caused by Gram-negative bacterial infections.

On the other hand, modified versions of lipid A can be used as components of vaccines (adjuvants) to improve their effect.^[5]

Mechanism of activating cells

Lipid A (and LPS) has been demonstrated to activate cells via Toll-like receptor 4 (TLR4), MD-2 and CD14 on the cell surface (Poltorak, Beutler et al., Blood Cells Mol Dis 1998)(Beutler, Poltorak, J Endotoxin Res 2000)(Park et al., Nature 2009). Consequently, lipid A analogs like eritoran can act as TLR4 antagonists. They are being developed as drugs for the treatment of excessive inflammatory responses to infections with Gram-negative bacteria.^[6]

References

^ ^a ^b ^c Raetz, Christian R. H.; Guan, Ziqiang; Ingram, Brian O.; Six, David A.; Song, Feng; Wang, Xiaoyuan; Zhao, Jinshi (2009). "Discovery of new biosynthetic pathways: the lipid A story". Journal of Lipid Research: S103–S108.
^ ^a ^b Raetz C, Whitfield C (2002). "Lipopolysaccharide endotoxins" (abstract). Annu Rev Biochem 71 (1): 635–700. doi:10.1146/annurev.biochem.71.110601.135414. PMC 2569852. PMID 12045108.
^ Tzeng YL, Datta A, Kolli VK, Carlson RW, Stephens DS (May 2002). "Endotoxin of Neisseria meningitidis composed only of intact lipid A: inactivation of the meningococcal 3-deoxy-D-manno-octulosonic acid transferase". J. Bacteriol. 184 (9): 2379–88. doi:10.1128/JB.184.9.2379-2388.2002. PMC 134985. PMID 11948150.
^ ^a ^b King, Jerry D; Kocíncová, Dana; Westman, Erin L; Lam, Joseph S (2009). "Lipopolysaccharide biosynthesis in Pseudomonas aeruginosa". Innate Immunity 15 (5): 261–312. doi:10.1177/1753425909106436. PMID 19710102.
^ Coler RN, Bertholet S, Moutaftsi M, Guderian JA, Windish HP et al. (2010). "Development and Characterization of Synthetic Glucopyranosyl Lipid Adjuvant System as a Vaccine Adjuvant". PLoS ONE 6 (1): e16333. doi:10.1371/journal.pone.0016333. PMC 3027669. PMID 21298114.
^ Tidswell, M; Tillis, W; Larosa, SP; Lynn, M; Wittek, AE; Kao, R; Wheeler, J; Gogate, J et al. (2010). "Phase 2 trial of eritoran tetrasodium (E5564), a Toll-like receptor 4 antagonist, in patients with severe sepsis". Critical Care Medicine 38 (1): 72–83. doi:10.1097/CCM.0b013e3181b07b78. PMID 19661804.

External links

Lipid A at the US National Library of Medicine Medical Subject Headings (MeSH)
The Lipid Library - Summary of Lipid A and bacterial polysaccharides

UpToDate Contents

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1. サルモネラ胃腸炎の病因 pathogenesis of salmonella gastroenteritis
2. 自然免疫系の概要 an overview of the innate immune system
3. ヘリコバクターピロリ感染の病態生理およびそれへの免疫応答 pathophysiology of and immune response to helicobacter pylori infection
4. 髄膜炎菌の微生物学および病理生物学 microbiology and pathobiology of neisseria meningitidis
5. コリスチン：概要 colistin an overview

English Journal

PepT1 mRNA expression levels in sea bream (Sparus aurata) fed different plant protein sources.

Terova G, Robaina L, Izquierdo M, Cattaneo A, Molinari S, Bernardini G, Saroglia M.SourceDepartment of Biotechnology and Life Sciences, University of Insubria, Via J.H. Dunant, 3 - 21100, Varese, Italy ; Inter-University Centre for Research in Protein Biotechnologies "The Protein Factory"- Polytechnic University of Milan and University of Insubria, Varese, Italy.
SpringerPlus.Springerplus.2013 Dec;2(1):17. Epub 2013 Jan 19.
The expression and regulation of intestinal oligopeptide transporter (PepT)-1 when vegetable sources are used as a substitute for fish meal in the diet of marine fish has not yet been explored. In the present study, as part of our ongoing work on elucidating PepT1 gene expression in relation to diff
PMID 23449729

The properties of chitosan complexes with smooth and rough forms of lipopolysaccharides on CHO-K1 cells.

Arabski M, Lisowska H, Lankoff A, Davydova VN, Drulis-Kawa Z, Augustyniak D, Yermak IM, Molinaro A, Kaca W.SourceDepartment of Microbiology, Jan Kochanowski University, Świętokrzyska 15, 25-406 Kielce, Poland. Electronic address: arabski@ujk.kielce.pl.
Carbohydrate polymers.Carbohydr Polym.2013 Sep 12;97(2):284-92. doi: 10.1016/j.carbpol.2013.05.008. Epub 2013 May 14.
The negative charge of LPS molecule and the presence of fatty acids in lipid A structure make it capable of binding with chitosan. In the presented work we analyzed the interactions of chitosan with LPS of Burkholderia cepacia or Proteus mirabilis and biological effects of these complexes on CHO-K1
PMID 23911447