Introduced species metabolites

Bark beetles oxidise toxic monoterpenoid hydrocarbons in their respiratory air, which originate from the resin of the tree they colonise, and thereby circumvent this defense barrier of the tree. Converting these compounds into less toxic secondary metabolites serves another purpose, by providing pheromones to attract insects of the same species, of both sexes. Therefore, an oxygen function is often introduced species-specifically and stereoselectively. European spruce bark beetles oxidise (-)-a-pinene to (S)-cis-verbenol, whereas pine beetles produce (R)-trans-verheno. In the California fivespined engraver Ips paraconfu-sus), myrcene is converted into (S)-ipsdienol and (S)-ipsenol. But Ips pint and Ips paraconfusus are also able to synthesise their pheromones de novo via the classical mevalonate biosynthetic pathway. 

In phase 1, the pollutant is converted into a more water-soluble metabolites, by oxidation, hydrolysis, hydration, or reduction. Usually, phase 1 metabolism introduces one or more hydroxyl groups. In phase 2, a water-soluble endogenous species (usually an anion) is attached to the metabolite— very commonly through a hydroxyl group introduced during phase 1. Although this scheme describes the course of most biotransformations of lipophilic xenobiotics, there can be departures from it. 

Table 16.2.2. Metabolites introduced with alien species...

Invading species/Geographic origin/Invaded area Metabolite introduced/Class of metabolite Bioactivity of metabolites... 

Still another experimental route to introducing otherwise excluded molecules into the brain is to chemically modify them so that they are lipophilic and therefore can passively diffuse. The brain, just as most other organs and tissues of the body, has enzymes to metabolize or biotransform metabolites in order to use and then get rid of them. Many of these pathways are oxidative. A reduced species or derivative which is lipophilic can enter the brain by simple passive diffusion there to be oxidatively transformed into an active state. Compounds which have been tested in animals include derivatives of 2-PAM (an antidote for organophosphate insecticide poisoning) and phenylethylamine (similar to amphetamine type molecules). Figure 5 illustrates the general concept behind this method. 

There occur marked differences between rodent species and humans in the proportions of a dose excreted as these various major metabolites, and the dose size introduces further variables. Mr et al. (1989) gave male Sprague-Dawley rats, BALB/c mice and Syrian hamsters 0.1,0.7 and 7 mmol/kg bw dimethylformamide (approximately 7,50 and 500 mg/kg bw) by intraperitoneal injection and collected urine for 60 h (rat), 24 h (mice) and 36 h (hamster). In all cases, dimethylfonnamide and AMCC were very minor urinary metabolites, while the amounts of substances analysed as W-methylformamide ... 

When chenodeoxycholic acid therapy was first introduced, there was some anxiety that this bile acid, or its bacterial metabolite lithcholic acid, might cause liver damage in man. This possible complication has not eventuated. Lithocholic acid is toxic to the liver in many animal species but in man, it is converted to sulfolithocholate and excreted (A5). Nevertheless, up to one-third of patients undergoing chenodeoxycholic acid treatment do show transient rises in serum levels of aspartate aminotransferase activity. The mechanism of this hypertransaminasemia is obscure, although it could possibly be related to lithocholate formation (D8). In any case, hepatotoxicity very rarely occurs at a clinically significant level (SI4). 

The rate of bile secretion and the pH of the bile may also be determinants of the extent of biliary excretion of a foreign compound, and these also show species variations. The fate of compounds excreted in the bile may also depend on the species, as differences in intestinal pH and flora occur. A particularly important consequence of biliary excretion is metabolism by the gut flora and reabsorption. This enterohepatic circulation prolongs the length of time the animal is exposed to the foreign compound, and may introduce novel toxic metabolites. This could therefore result in marked species differences in toxicity. 

Unlike the situation for conventional nutrients such as vitamins and minerals, where the role in disease prevention and recommended levels are both understood, the situation for phytochemicals remains obscure. Crucial decisions need to be made as to which secondary metabolites, individual or group, should be manipulated, to what level(s), in which crops to facilitate optimum nutritional and health benefits. Given that attempts to increase, for example, brassica consumption generally founder on the rock of well-established food preferences, would it be better to enhance sulforaphane levels in brassicas or to introduce the relevant genes and controls into other, more widely consumed species Of course, one option does not exclude the other. 

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