Hepaticae lipids

Although sterols like cholesterol are not synthesized de novo by parasitic flatworms, they do possess an active mevalonate pathway (Fig. 20.3) (reviewed in Coppens and Courtoy, 1996). This pathway has been studied in 5. mansoni, and all available evidence indicates that it is similar to the lipid metabolism seen in F. hepatica. The mevalonate pathway was shown to be used by 5. mansoni for the synthesis of dolichols for protein glycosylation, of quinones as electron transporters in the respiratory chain and of farnesyl and geranylgeranyl pyrophosphates as substrates for the isopreny-lation of proteins (Chen and Bennett, 1993 Foster et a/., 1993). A key enzyme in the mevalonate pathway is 3-hydroxymethylglutaryl-CoA reductase (HMG-CoA reductase) and it was shown that the schistosomal enzyme differs from the mammalian type, both structurally and in its regulatory properties (Rajkovic et ai, 1989 Chen et at., 1991). Farnesyl pyrophosphate plays a key role in the mevalonate pathway as it is the last common substrate for the synthesis of all end products (Fig. 20.3). As mentioned already, the branch leading from farnesyl pyrophosphate via squalene to cholesterol is not operative in parasitic flatworms, whereas the other branches are active, at least in S. mansoni and probably also in F. hepatica and FI. diminuta. 

It is not only fatty acids that are modified (see section on Lipids ) in parasitic flatworms, but also cholesterol obtained from the host is not only used directly as a component of membranes in F. hepatica and 5. mansoni, but it is also used as a substrate for the synthesis of other compounds such as ecdysteroids (Foster etal., 1992). 

A few other less studied biochemical approaches such as purine and pyrimidine metabolism protein biosynthesis and lipid metabohsm in helminths also provide targets for antiparasitic drug design [83]. Like protozoal parasites, some helminths such as S. mansoni (adult and larval forms) lack de novo purine biosynthesis and, therefore, depend entirely on the salvage mechanism for their purine requirements. Similarly amino acid metabolism and biosynthesis of proteins has also been not worked out in many parasites [83a]. Although the helminths meet their requirements of amino acids by absorbing freely from the host, they may also synthesize some amino acids. For example. Fasciola hepatica, schistosomes and other trematodes produce proline by a reaction sequence given in Chart 8. Similarly H. diminuta can... 

F. hepatica is much thicker and less pitted than that of schistosomes. It is bounded externally by a standard lipid bilayer from which extends a thin coat of glycoprotein... 

Lipids also function as antimicrobial agents in the skin of mammals (Nico-laides, 1974), antidesiccants in the cuticle of insects (Holloway, 1984), and bioacoustic lenses in dolphins (Ackman et al., 1975). A special structure known as the elaisome located in the seeds of numerous species of plants release lipids, particularly diacylglycerols, that attract ants (Marshall et al., 1979). A study by Skidmore and Heithaus (1988) used TLC to show that ants responded rapidly to the elaisomes or the diacylglycerol fraction of the elaisomes of seeds of the perennial herb Hepatica americana. 

Skidmore, B. A., and Heithaus, E. R. (1988). Lipid cues for. seed-carrying by ants in Hepatica americana. J. Chem. Ecol. 14 2185—2196. 

Early studies on the chemistry of the bryophytes have been summarized by Benesova and Herout 86), Hegnauer 141), Huneck 150 —153,156), Martensson and Nilsson 205a), Spencer 303) and Suire 307). A review of heterocyclic compounds found in the bryophytes was also presented (37). Recently, Markham and Porter 199) have reviewed the chemical constituents of the bryophytes their review includes sesquiterpenoids, water soluble flavonoids, lignins, lipids and bibenzyls published prior to 1978, flavonoid chemistry and chemosystematic approaches to the Marchantiales being discussed in detail. In the three years since publication of this review, 121 papers on the chemistry of the Hepaticae have been published. 

Table II. Chemical Constituents (Lipids and Miscellaneous) Found in the Hepaticae ... 

Table II. Chemical constituents (lipids and miscellaneous) found in the Hepaticae. 175—185...

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