Lipid carrier isoprenoid

Figure 1.11 Structure of the Lipid Carrier Isoprenoid, Undecaprenyl Phosphate...

At one time, the lipid carrier was believed to be a glycerophos-phatide, but further purification showed conclusively that it is a Cjs-isoprenoid alcohol phosphate. Its nuclear magnetic resonance spectrum showed that two of its internal double bonds have the trans configuration, and that this isoprenoid alcohol differs from ficaprenol, a Cjs-isoprenoid alcohol from fig leaves, which has three internal, trans, double bonds. ... 

Isoprenoid lipid carriers are used to convert the hydrophilic nucleotide diphosphate sugars into a form that is able to penetrate the cytoplasmic membrane. It will be recalled that isoprenoid sugar carriers are also used in the biosynthesis of peptidoglycan (p. 14) and LPS (p. 79). In actively growing bacteria there must be sufficient sugar-charged isoprenoid carrier... 

There are two mechanisms by which lipids may participate in enzymic systems. Gly-cerophosphatides act as enzymic cofactors modifying protein structure but they do not participate directly in catalytic processes. Other lipids are acceptors of a substrate in a reaction and act as donors of it in a second one. These lipids are called lipid carriers and have been characterized as phosphates or pyrophosphates of isoprenoid alcohol. The fact that these lipids are found in particulate preparations suggests that they may give the sugars the lipophilic characteristics needed to pass through membranes. 

The participation of polyprenol sugar phosphates as intermediates in the biosynthesis of several types of complex carbohydrate has been clearly established in bacteria (for a review see ref. 11). Tanner in 1969< > presented the first evidence of the possible participation of lipid carriers in yeast. This was confirmed by us and the carrier was found to be a phosphodiester of mannose and an isoprenoid alcohol.Finally, Jung and Tanner purified a lipid which was able to accept mannose from GDP-mannose when added exogenously to a particulate preparation. This lipid was characterized as a dolichol phosphate. 

It has been well established that the enzymes required for the biosynthesis of the polymers of the outer membrane are localized in the inner membrane. Most importantly, the lipid-carrier molecules (poly-isoprenoid-phosphates) are found in this membrane. These molecules transfer newly synthesized, activated precursor molecules from the hydrophilic cytoplasmic environment into the lipophilic environment of the membrane, where the assembly into polymeric structures takes place. This assembly process is used for lipopolysaccharides, peptidoglycans, and capsular polysaccharides. In a subsequent step, the membrane-carrier molecules transfer the assembled polymers from the inner to the outer membrane. ... 

The O-antigen is made in three stages. The oligosaccharide units are transferred from nucleotide diphosphate carriers to a galactose attached to another lipid carrier a 55 carbon polyisoprenoid molecule. The oligosaccharide units are then polymerized and lipid carriers are released in the process. Finally, the complete O-antigen is transferred to the R-core, with the release of the final isoprenoid carrier. 

In addition to NAD and flavoproteins, three other types of electron-carrying molecules function in the respiratory chain a hydrophobic quinone (ubiquinone) and two different types of iron-containing proteins (cytochromes and iron-sulfur proteins). Ubiquinone (also called coenzyme Q, or simply Q) is a lipid-soluble ben-zoquinone with a long isoprenoid side chain (Fig. 19-2). The closely related compounds plastoquinone (of plant chloroplasts) and menaquinone (of bacteria) play roles analogous to that of ubiquinone, carrying electrons in membrane-associated electron-transfer chains. Ubiquinone can accept one electron to become the semi-quinone radical ( QH) or two electrons to form ubiquinol (QH2) (Fig. 19-2) and, like flavoprotein carriers, it can act at the junction between a two-electron donor and a one-electron acceptor. Because ubiquinone is both small and hydrophobic, it is freely diffusible within the lipid bilayer of the inner mitochondrial membrane and can shuttle reducing equivalents between other, less mobile electron carriers in the membrane. And because it carries both electrons and protons, it plays a central role in coupling electron flow to proton movement. 

In addition to its role as an intermediate in cholesterol biosynthesis, isopentenyl pyrophosphate is the activated precursor of a huge array of biomolecules with diverse biological roles (Fig. 21-48). They include vitamins A, E, and K plant pigments such as carotene and the phytol chain of chlorophyll natural rubber many essential oils (such as the fragrant principles of lemon oil, eucalyptus, and musk) insect juvenile hormone, which controls metamorphosis dolichols, which serve as lipid-soluble carriers in complex polysaccharide synthesis and ubiquinone and plastoquinone, electron carriers in mitochondria and chloroplasts. Collectively, these molecules are called isoprenoids. More than... 

The way in which a polysaccharide is released from the isoprenoid lipid is not yet known. Most probably, enzymes are present that cleave the terminal, phosphate-linked, monosaccharide residue. The chain length of a polysaccharide may depend on the growth rate that is, a higher growth-rate might lead to a faster turnover of the carrier lipid and release of polysaccharide of lower molecular weight. Instances are known where variable chain-length results from the action of depolymerases.239... 

Essentially the same consideration appUes to an inverted bicontinuous cubic phase (Qn) and an inverted hexagonal (Hn) phase, which are usually formed with lipids with long hydrophobic chains. Qn and Hn phases have recently received growing attention in the pharmaceutical or biological fields, for instance, as new carriers for drug-deUvery systems, and matrices for membrane protein crystallization [37-42]. The conventional (e.g., monoolein) Qn phase, however, often transforms into a soUd phase at low temperatures around 4°C [43-47], where temperature-sensitive proteins or actives are most preferably handled and preserved. It has recently been confirmed that isoprenoid-chained lipids can in fact give a range of Qn phases that are stable at low temperatures [13]. 

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