Isoprenoid metabolites

Recently, a potential cytosolic component of the MEP precursor pathway, xylulose kinase, has been cloned and tested for function in an Escherichia coli complementation system. " The kinase activates exogenous xylulose in the cytoplasm. DXP is the precursor for DXS, which resides in the plastid, suggesting the activated substrate must be transported into the plastid. Another xylulose kinase homologue in Arabidopsis that contains a plastid targeting sequence was not active in the E. coli system, suggesting that it may have some other function in the plastid. Perhaps plant and bacterial tissue cultures may be fed xylulose to condition accumulation of isoprenoid metabolites. 

A metabolite, molecular entity, or some other event/ process that precedes another component in a longer sequence of events or conversions. For example, the isoprenoid metabolite squalene is a precursor of cholesterol and glucose 6-phosphate is a precursor of glycogen, ribose, and pyruvate. See Series First Order Reaction Pulse-Chase Experiments... 

Members of the polyphyletic order Lithistida have been reported to contain 42 acetogenins (38%) and 49 amino acids (44%), with only 21 isoprenoid metabolites (19%). The order currently termed Lithistida probably arose from more than one divergence event in the past,56 and may... 

Marine macroalgae produce a wide variety of intriguing and diverse isoprenoid structures derived from C5 isoprene units, and many reports have been published on the ecological roles of these metabolites. Marine terpenoids are frequently found with halogenated functionalities and one or more rings, which can have important implications for their biological activities. Isoprenoid metabolites are derived via the classical mevalonate pathway or the more recently discovered deoxyxylulose phosphate pathway. Isoprenoids are... 

Solanesol and other prenyl alcohols are important as metabolites in mulberry and tobacco leaves and in the synthesis of isoprenoid quinones. Hence, Sato and collaborators107 have developed a stereoselective synthesis of all-trans-polyprenol alcohols up to C50. Construction of the requisite skeletons was accomplished by the alkylation of a p-toluenesulphonyl-stabilized carbanion, followed by reductive desulphonylation of the resulting allylic sulphonyl group. This was achieved most efficiently by the use of a large excess of lithium metal in ethylamine (equation (43)), although all reaction conditions led to mixtures. The minor product results from double bond rearrangement. 

LANGE, B.M., KETCHUM, R.E.B., CROTEAU, R., Isoprenoid biosynthesis metabolite profiling of peppermint oil gland secretory cells and application to herbicide target analysis, Plant Physiol., 2001,127, 305-314. 

More than half of the reported secondary metabolites from macroalgae are isoprenoids. Terpenes, steroids, carotenoids, prenylated quinines, and hydroqui-nones make up the isoprenoid class, which is understood to derive from either the classical mevalonate pathway, or the mevalonate-independent pathway (Stratmann et al. 1992). Melavonic acid (MVA) (Fig. 1.2) is the first committed metabolite of the terpene pathway. Dimethylallyl (dl meth al lal) pyrophosphate (DMAPP) (Fig. 1.3) and its isomer isopentenyl pyrophosphate (IPP, Fig. 1.3) are intermediates of the MVA pathway and exist in nearly all life forms (Humphrey and Beale 2006). Geranyl (ja ran al) (C10) and famesyl (C15) units are generated by head-to-tail (Fig. 1.3) condensation of two (for C10) or three (for C15) 5-carbon DMA-like isoprene units, identifiable in final products by the characteristic fish-tail repeating units, as traced over the structure of a sesquiterpene in Fig. 1.3 (Humphrey and Beale 2006). Additional IPP condensation with famesyl pyrophosphate (FPP)... 

Cvejic JH, Rohmer M (2000) C02 as main carbon source for isoprenoid biosynthesis via the mevalonate-independent methylerythritol 4-phosphate route in the marine diatoms Phaeodactylum tricomutum and Nitzschia ovalis. Phytochemistry 53 21-28 de Nys R, Steinberg PD, Willemsen P, Dworjanyn SA, Gabelish CL, King RJ (1995) Broad-spectrum effects of secondary metabolites from the red alga Delisea pulchra in antifouling assays. Biofouling 8 259-271... 

For each biome, the metabolites are grouped per chemical class in graphical charts, in tte order alkaloids, peptides (including also depsipeptides, lipopeptides, and glycopeptides), polypeptides, isoprenoids, frtty acids and polyketides, shikimates, and carbohydrates. Attention is also paid to... 

Chemical bias toward certain molecular arrangements may also determine the commonness of certain metabolites (Pietra 1995), such as the aplysinopsins (indole alkaloids of many sponges, cnidarians, and mollusks. Chart 8.2. A), bis-indole and guanidine alkaloids (Chart 8.2.A), isoprenoids (Pietra 1995, Chart 8.2.1), and polypropionates of mollusks, sponges, and fungi (Chart 8.2.FA/PO). 

In the past decade, eight inherited disorders have been linked to specific enzyme defects in the isoprenoid/cholesterol biosynthetic pathway after the finding of abnormally increased levels of intermediate metabolites in tissues and/or body fluids of patients (Table 5.1.1) [7, 9, 10]. Two of these disorders are due to a defect of the enzyme mevalonate kinase, and in principle affect the synthesis of all isoprenoids (Fig. 5.1.1) [5]. The hallmark of these two disorders is the accumulation of mevalonic acid in body fluids and tissues, which can be detected by organic acid analysis, or preferably, by stable-isotope dilution gas chromatography (GC)-mass spectrometry (GC-MS) [2]. Confirmative diagnostic possibilities include direct measurement of mevalonate kinase activities in white blood cells or primary skin fibroblasts [3] from patients, and/or molecular analysis of the MVK gene [8]. 

As presented in Table 1.2, over half of reported marine natural products are derived from the isoprenoid biosynthetic pathway (56%), with the remainder split mainly between amino acid (19%) and acetogenin (20%) pathways. Secondary metabolites falling into the categories of nucleic acids and carbohydrates comprise only 1%. Such low levels are somewhat surprising given the fundamental importance of such classes of compounds as primary metabolites. 

Metabolites of the phylum Porifera account for almost 50% of the natural products reported from marine invertebrates. Of the 2609 poriferan metabolites, 98% are derived from amino acid, acetogenin, or isoprenoid pathways. Isoprenoids account for 50% of all sponge metabolites, while amino acid and polyketide pathways account for 26% and 22%, respectively. A significant number of sponge metabolites appear to be derived from mixed biosynthetic pathways. Most structures reported containing carbohydrate moieties were glycosides. 

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