Lipid bacterial cell wall

Dworzanski, J. R Berwald, L. McClennen, W. H. Meuzelaar, H. L. C. Mechanistic aspects of the pyrolytic methylation and transesterification of bacterial cell wall lipids. /. Anal. Appl. Pyrolysis 1991,21,221-232. 

Hydroxy or a-hydroxy acids have been shown to occur in sphingolipids, skin lipids, wool wax, bacterial cell wall lipids and in some seed oils. 3-Hydroxy or 3-hydroxy acids are present in bacterial lipids. 

Among the important glycolipids, which are combinations of carbohydrate and lipid, are the cerebrosides and gangliosides. These are constituents of brain and nervous tissue and are usually considered with lipids because they are water-insoluble. Water-soluble polymers of high relative molecular mass containing lipid and carbohydrate, known as lipopolysaccharides, are found in bacterial cell walls. 

Evidence of a role of lipid peroxidation in the cellular toxicity of ozone has been obtained in in vitro studies in which human red cells were exposed to this oxidant gas. The possibility that lipid peroxidation is responsible for altered permeability of bacterial cell walls after ozone exposure was proposed by Scott and Lesher and has since been con-... 

Bacitracin (Fig. 4) is a cyclic peptide antibiotic. The lipid II molecule involved in the bacterial cell wall biosynthesis has a C55 isoprenyl pyrophosphate moiety that must be dephosphorylated so that it can reparticipate in another round of lipid II transfer. Bacitracin binds to the isoprenyl pyrophosphate and prevents the dephosphorylation which, in turn, blocks cell wall growth by interfering with the release of the muropeptide subunits to the outside of the bacterial cell membrane. Bacitracin inhibits similar reactions in eukaryotic cells. So, it is systemically toxic but is an effective and widely used topical antibiotic. 

As components of bacterial cell walls, LPS and lipids A are first recognized by the cells of the innate immune system and are able to activate them. 

Lipid-Linked Oligosaccharides Are Precursors for Bacterial Cell Wall Synthesis... 

Synthesis of the bacterial cell wall peptidoglycan also involves lipid-linked oligosaccharides formed inside the cell and flipped to the outside for assembly. 

Many of the proteins of membranes are enzymes. For example, the entire electron transport system of mitochondria (Chapter 18) is embedded in membranes and a number of highly lipid-soluble enzymes have been isolated. Examples are phosphatidylseiine decarboxylase, which converts phosphatidylserine to phosphatidylethanolamine in biosynthesis of the latter, and isoprenoid alcohol phosphokinase, which participates in bacterial cell wall synthesis (Chapter 20). A number of ectoenzymes are present predominantly on the outsides of cell membranes.329 Enzymes such as phospholipases (Chapter 12), which are present on membrane surfaces, often are relatively inactive when removed from the lipid environment but are active in the presence of phospholipid bilay-ers.330 33 The distribution of lipid chain lengths as well as the cholesterol content of the membrane can affect enzymatic activities.332... 

The outer surfaces of bacteria are rich in specialized polysaccharides. These are often synthesized while attached to lipid membrane anchors as indicated in a general way in Eq. 20-20.136/296a One of the specific biosynthetic cycles (Fig. 20-9) that depends upon undeca-prenol phosphate is the formation of the peptidoglycan (murein) layer (Fig. 8-29) of both gram-negative and gram-positive bacterial cell walls. Synthesis begins with attachment of L-alanine to the OH of the lactyl... 

In the polymers of groups (1) and (2), polysaccharide chains composed of oligosaccharide repeating-units (sometimes, partially modified) are usually linked to a unique oligosaccharide unit present near the point of attachment of the chain to another polymeric chain, or to a lipid anchor. This unit is called the linkage region in the polymers of bacterial cell-wall, and the core region in lipopolysaccharides. 

TOTAL SYNTHESIS OF LIPID I AND LIPID II LATE-STAGE INTERMEDIATES UTILIZED IN BACTERIAL CELL WALL BIOSYNTHESIS... 

In summary, we were able to develop a chemically robust synthetic route to lipid I, the penultimate intermediate utilized in bacterial cell wall biosynthesis. The identification of a method for stereoselective introduction of the anomeric phosphate and a protocol to enable diphosphate coupling were pivotal to our success and ultimately provided the precedent for our chemical synthesis of lipid II detailed in the sections that follow. 

M Matsuhashi. Utilization of lipid-linked precursors and the formation of peptidoglycan in the process of cell growth and division membrane enzymes involved in the final steps of peptidoglycan synthesis and the mechanism of their regulation. In JM Ghuysen, R Hakenbeck, eds. Bacterial Cell Wall. Amsterdam, The Netherlands Elsevier Science, 1994, pp 55-72. 

J Kato, S Fujisaki, K Nakajima, Y Nishimura, M Sato, A Nakano. The Escherichia coli homologue of yeast RER2, a key enzyme of dolichol synthesis is essential for carrier lipid formation in bacterial cell wall synthesis. J Bacteriol 181 2733-2738, 1999. 

The peptidoglycan layer confers mechanical stability to the cell wall of the bacteria. An important intermediate of the peptidoglycan biosynthesis is the GlcNAc- MurNAc-L-Ala-D-y-Gln-L-Lys-D-Ala-D-Ala peptide (muramyl-pentapeptide), which is in its lipid-carrrier bound form transglycosylated to a linear polysaccharide. The linear polysaccharide is then cross-linked to peptidoglycan by transpeptidation reactions. Perkins observed that vancomycin binds to the Lys-D-Ala-D-Ala peptide motif of bacterial cell wall intermediates. This observation was later investigated on a mole-cular level by NMR and by x-ray crystallographic studies. ... 

Penicillin interferes with the synthesis of the bacterial cell wall. A nucleophilic OH group of the glycopeptide transpeptidase enzyme cleaves the P-lactam ring of penicillin by a nucleophilic acyl substitution reaction. The opened ring of the penicillin molecule remains covalently bonded to the enzyme, thus deactivating the enzyme, halting cell wall construction, and killing the bacterium. Penicillin has no effect on mammalian cells because they are surrounded by a flexible membrane composed of a lipid bilayer (Chapter 3) and not a cell wall. 

The participation of a nucleotide-activated disaccharide and UDP-activated peptide intermediates are unique features of pseudomurein biosynthesis. Usually, oligosaccharide precursors of bacterial cell-wall polymers are formed at the lipid stage [38,44] and amino acids carrying a nucleotide residue at the. /V -amino group have not been found in nature so far. The distinct differences between the two biosynthetic routes support the hypothesis that murein and pseudomurein represent independent inventions made after the domains bacteria and archaea had been separated from each other during evolution [40,46]. 

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