Lipid precursor

Utilizing such lipid precursors, several holothuroids were shown to be capable of de novo production of 4- and 4,4-demethyl sterols, but incapable of further steroid elaboration (Scheme 3) [15]. The incorporation of sterol precur-... 

The aliphatic alicyclic hydrocarbon precursor is not well recognized as the major aliphatic component in dissolved humic substances, although it was previously postulated to occur (II). This precursor might arise from terpenoid hydrocarbon lipids, but the data presented in this chapter favor polyunsaturated lipid precursors that are oxidatively coupled and cyclized by free-radical mechanisms (20). Degradative studies have not identified this aliphatic component in recognizable fragments. The quantitative, structural-model approach presented here combines the results of 13C NMR, NMR,... 

Similar concerns regarding the stability of our activated lipid intermediate led us to reject a method that involves the in situ preparation of lipid-derived phosphoric anhydrides.22 The common theme for each of the methods illustrated above is that each involves activation of the lipid intermediate for the diphosphate coupling reaction. Given the expense of the undecaprenyl monophosphate precursor, we sought a method that would entail activation of the carbohydrate fragment for capture by an undecaprenyl monophosphate nucleophile. This, in principle, would also allow the opportunity for the coupling reaction to take place under basic reaction conditions and enable us to preserve the chemical integrity of our expensive lipid precursor. 

The lipid composition changes dramatically during terminal differentiation. After extrusion from the lamellar bodies, the polar lipid precursors are enzymatically converted into more hydrophobic lipids. As a result, phospholipids are almost absent in the stratum corneum. The lipid lamellae surrounding the corneocytes are predominantly composed of ceramides, cholesterol, and free fatty acids. It is generally assumed that these lipids are present in nearly equimolar ratios. However, inspection of literature data shows that there is a high interindividual variability in the lipid composition [37],... 

A third mode of entry of Ca2+ into the cells is mediated by the coupling of the receptor to G proteins. It is believed that this is the pathway used by chemokines. The On reaction begins when the agonist induces a conformational change in the receptor which is transmitted to the G protein. The heterodimeric G protein dissociates into Ga and G 3y subunits, both of which can activate different phospholipase C (PLC) isozymes. This enzyme is able to catalyze the hydrolysis of the lipid precursor phosphatidylinositol 4,5-bisphosphate to give both 1,2-diacylglycerol (DAG) and inositol 1,4,5-trisphosphate (IP3). The latter then binds to the IP3 receptor which mobilizes both stored Ca2+ and promotes an influx of external Ca2+. 

Fig. 8A.2 Major grape unsaturated acyl lipids, precursors of C6 compounds...

Figure 2 The "inositol cycle." Asimplified representation of the regenerative metabolism responsible for the synthesis of lnsP3. Generation of lnsP3and DAG upon PLC-mediated hydrolysis of Ptdlns(4,S)P2 is followed by sequential dephosphorylation of lnsP3and DAG s modification to CDP-DAG. The enzymatic attachment of CDP-DAG to inositol regenerates the lipid precursors that ultimately replenish Ptdlns(4,S)P2.

As mentioned earlier, the lymphatic system is poorly developed in poultry. Absorbed lipids pass into the portal circulation and then are principally transported as triacylglycerols of the VLDL fraction. VLDLs are present in the serum at high concentrations and appear to be the major lipid precursor in the liver for egg yolk synthesis. Furthermore, fats high in unsaturated fatty acids are absorbed more readily than fats low in unsaturated fatty acids (51, 54). 

Complete elimination of macromolecules is desirable for many purposes but is also the most difficult to achieve. The first such medium was MCDB 302, derived in Ham s laboratory to support clonal cell growth of Chinese hamster ovary (CHO) cells without deliberate attempts to adapt cells in protein-free medium. This medium contains solely amino acids, vitamins, organic compounds and inorganic salts to replace fully the functions of serum rather than to develop new cell lines that do not need serum. More recently, nearly protein-free media have been developed for murine hybridomas, lymphocytes and hepatoma cells. These media may contain steroid hormones and lipid precursors. 

Initiation includes synthesis of the oligosaccharide-lipid precursor and transfer of the oligosaccharide to a protein. Evidence for a possible role for retinol (vitamin A) as a carrier in this step is discussed in Chapter 38. 

The essential features of most modem views of abiogenesis (Figure 2C) include an early phase in which organic molecules were formed. During a later phase, it is presumed that primitive celllike structures, called protocells, enclosed by lipid precursor molecules possessed a richer diversity of organic molecules. Within the confines of protocells, certain monomer molecules polymerized to form polypeptides and nucleic acids. 

We found the principal FAs upon infection to be oleic acid (18 1) and saturated FAs. The most characteristic increases in FAs were in palmitic (16 0), which went from 19% to 28%, stearic (18 0) from 10% to 14% and oleic (18 1) from 18% to 28%. The relative paucity of polyunsaturates in PLs led us to suggest that there were defects in appropriate desaturases, chain elongation systems and acylation enzymes and we concluded that the malaria parasite, though it may have no capacity for de novo biosynthesis of lipids from acetate, can regulate its use of host cell lipids and lipid precursors in such a manner as to establish and maintain a lipid composition distinct in many respects from that of the erythrocyte (Beach et al., 1977). 

DHAP can be diverted from its precursor role in ether lipid synthesis by conversion to jn-glycerol-3-phosphate by NADH glycerol-3-phosphate dehydrogenase. Another bypass that prevents the formation of alkyl-DHAP occurs if the ketone function of acyl-DHAP is first reduced by an NADPH-dependent oxidoreductase, since the product, l-acyl-2-lyso-in-glycerol-3-phosphate, can then be converted only to diacylglycerolipids. The metabolic removal and/or formation of fatty alcohols, DHAP, or acyl-DHAP from the ether lipid precursor pool may control ether lipid synthesis and accumulation. 

The transbilayer movement of phospholipids in microsomal membranes has been measured using several different approaches. Phospholipid transfer proteins were used to probe the transbilayer movement of lipids in preparations of liver microsomes that were first radiolabeled with lipid precursors in vivo (D.B. Zilversmit, 1977). The results from these experiments provided evidence that PC, PE, PS, and PI from both membrane leaflets were exchanged between labeled microsomes and excess acceptor membranes with a maximal t 2 of 45 min. 

Similarly to T. cruzi, inositol phospholipids have been identified in T. brucei brucei (44). Moreover, two distinct PI synthase activities (CDP-diglyceride-dependent and -independent) are present in membrane fractions. In the absence of added lipid precursor, the incorporation of free inositol into PI is strongly stimulated by the addition of Mn " and less by Mg . Addition of exogenous CDP-diglyceride to the system increases the uptake of inositol by a factor of 1.5 to 3.5. These inositol phosphates may mediate part of the T. brucei brucei response to external signals. Previous work have shown that transformation of bloodstream forms to procyclic cells can be induced by cis-aconitate or citrate. Analysis of inositol phosphates in [ H]inositol-labeled cells exposed to ds-aconitate revealed that levels of InsP3 increased rapidly (maximum levels at one hour) and subsequently returned to basal level. The levels of InsP and InsP2 were not or little affected by cis-aconitate. 

Glycerol absorption in H. diminuta occurs by passive diffusion at high concentrations (>0.5mM) and by a carrier-mediated process at lower concentrations. At lower concentrations, absorption of this lipid precursor is non-linear, dependent on temperature and pH, and competitively inhibited by glycerol and a-glycerophosphate. The existence of two distinct carriers for this molecule is suggested by studies which show that only about half the saturable component in H. diminuta is Na -sensitive and inhibitable by 1,2-propandiol (2). 

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