Isoprene, metabolism

Isoprene metabolism in plants is very complex. Plants can synthesize many types of aromatic substances and volatile oils from isoprenoids. Examples include menthol (1= 2 ), camphor (1 = 2), and citronellal (1 = 2). These Cio compounds are also called monoterpenes. Similarly, compounds consisting of three isoprene units (1 = 3) are termed sesquiterpenes, and the steroids (1 = 6) are called triterpenes. 

Gervasi, P.G., Citti, L., Del Monte, M.. Longo, V. Benetti, D. (1985) Mutagenicity and chemical reactivity of epoxidic intermediates of the isoprene metabolism and other structurally related compounds. Mutat. Res., 156. 77-82... 

Acetyl-CoA is an "activated" two carbon compound found in many central metabolic pathways, including the citric acid cycle, the glyoxylate cycle, fatty acid synthesis, fatty acid oxidation, isoprene metabolism, amino sugar metabolism, ketone body metabolism, and cholesterol biosynthesis. The term "activated" used to describe the compound comes partly from the nature of the high energy... 

Tertiary thiols (Table 5.35) are some of the most intensive aroma substances. They have a fruity odor at the very low concentrations in which they occur in foods. With increasing concentration, they smell of cat urine and are called catty odorants. Tertiary thiols have been detected in some fruits, olive oil, wine (Scheurebe) and roasted coffee (Table 5.35). They make important contributions to the aroma and are possibly formed by the addition of hydrogen sulfide to metabolites of isoprene metabolism. In beer. 

IPP and its DMAPP structural isomer are produced from glycolytic products by the methyl erythritol phosphate (MEP) pathway (Figure 5.3.1, Pathway 1). These isoprene units are condensed in a stepwise fashion to form the precursor to all carotenoids, geranylgeranyl di-phosphate (GGPP). GGPP is not solely metabolized to make carotenoids, but is a precursor for many other primary and secondary metab-... 

In plant plastids, GGPP is formed from products of glycolysis and is eight enzymatic steps away from central glucose metabolism. The MEP pathway (reviewed in recent literature - ) operates in plastids in plants and is a preferred source (non-mevalonate) of phosphate-activated prenyl units (IPPs) for plastid iso-prenoid accumulation, such as the phytol tail of chlorophyll, the backbones of carotenoids, and the cores of monoterpenes such as menthol, hnalool, and iridoids, diterpenes such as taxadiene, and the side chains of bioactive prenylated terpenophe-nolics such as humulone, lupulone, and xanthohumol. The mevalonic pathway to IPP that operates in the cytoplasm is the source of the carbon chains in isoprenes such as the polyisoprene, rubber, and the sesquiterpenes such as caryophyllene. 

From activated isoprene, the metabolic pathway leads via dimerization to activated geraniol (1 = 2) and then to activated farnesol = 3). At this point, the pathway divides into two. Further extension of farnesol leads to chains with increasing numbers of isoprene units—e.g., phytol (1 = 4), dolichol (1 = 14-24), and rubber = 700-5000). The other pathway involves a head-to-head linkage between two farnesol residues, giving rise to squalene (1 = 6), which, in turn, is converted to cholesterol (1 = 6) and the other steroids. 

The pentose phosphate pathway (PPP, also known as the hexose monophosphate pathway) is an oxidative metabolic pathway located in the cytoplasm, which, like glycolysis, starts from glucose 6-phosphate. It supplies two important precursors for anabolic pathways NADPH+H+, which is required for the biosynthesis of fatty acids and isopren-oids, for example (see p. 168), and ribose 5-phosphate, a precursor in nucleotide biosynthesis (see p. 188). 

Isoprene is fonned endogenously at the rate of 1.9 imol/kg per hour in both rats and mice. l,2-Epoxy-2-methyl-3-butene (80%) and 3,4-cpoxy-2-mcthyl-1-butene (20%) are two major metabolites in mouse liver microsomes. The 3,4-epoxide can be further metabolized to isoprene diepoxide. Both rats and mice exhibited saturation kinetics when exposed to isoprene at concentrations above 300 ppm [837 mg/m ]. The maximal rate of metabolism in vivo is more than three times greater in mice than in rats (lARC, 1994). 

A physiological toxicokinetic model has been developed for inhaled isoprene in mouse, rat and humans, taking into account published or assumed kinetic parameters (Filser et al., 1996). On the basis of this model, at human exposure conditions (up to 50 ppm [140 mg/m3]), rates of metabolism are about 14 times faster in mice and about eight times faster in rats than in humans. 

The terpenoids are secondary metabolites that are found in essential oils, resins, tissues of higher plants and micro-organisms, whilst recently some have also been located in liverworts [5,6]. The terpenoids are formed from linear arrangements of isoprene units, Fig. (1), which are derived from acetate metabolism through mevalonic acid (MVA). This pathway was found to be common to the whole range of natural terpenoid derivatives... 

Pantothenic acid participates as part of coenzvme A in carbohydrate metabolism (2-carbon transfer-acetate, or pyruvate), lipid metabolism (biosynthesis and catabolism of fatty acids, sterols, +phospholipids), protein metabolism (acetylations of amines and amino acids), porphyrin metabolism, acetylcholine production, isoprene production. 

The biochemical isoprene units may be derived by two pathways, by way of intermediates mevalonic acid (MVA) (Figure 5.4) or 1-deoxy-D-xylulose 5-phosphate (deoxyxylulose phosphate DXP) (Figure 5.6). Mevalonic acid, itself a product of acetate metabolism, had been established as a precursor of the animal sterol cholesterol, and... 

The incorporation of label from mevalonate into ABA, a sesquiterpenoid, has been demonstrated in different parts of plants ( . . 41). This indicates that ABA can be synthesized throughout the plant. In addition to the direct incorporation of three isoprene units, derived from mevalonate, into ABA, an indirect biosynthetic pathway via carotenoids has been proposed. This idea stems from the finding that xanthophylls, in particular violaxanthin, can either photochemically or enzymatically be converted to the neutral inhibitor xanthoxin (42) (Figure 3). When labeled xanthoxin was fed in the transpiration stream to bean or tomato shoots, ca. 10% was converted to ABA over an 8-hr period (43). However, the importance of the biosynthetic route to ABA via xanthophylls and xanthoxin in normal metabolism remains to be established, and most of the evidence favors the direct synthesis route via a precursor (see 2). 

All secondary products are derived ultimately from compounds originated during primary metabolism such as sugars, acetate, isoprene, amino acids, and so on. 

The biologic precursors of isoprene units are isopentenyl diphosphate 7 (IPP) and dimethylallyl diphosphate 8 (DMAPP). These precursors can be obtained by two different metabolic pathways the mevalonate (MVA) pathway (Fig. 1), which was the first one to be elucidated, and the long-overlooked methylerythritol phosphate (MEP) pathway (Fig. 3) (1, 2). 

Similar experiments performed on ginkgo embryos also revealed an unexpected labeling pattern of the isoprene units of the diterpenoid skeletons. In this case, glucose is metabolized via glycolysis and a retrobiosynthetic analysis was in accordance with the formation of isoprene units from pyruvate and from a triose phosphate derivative (Fig. 5b) (3). 

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