Localization of alkaloids in the plant

Chewing leaves of the khat shrub is practiced in parts of East Africa and the Arabian peninsula (Kalix 1988 Widler et al. 1994). Some estimate daily use at 5 million portions. Use in the West is less common, but has increased somewhat. More common in the United States has been use of the synthetic drug methcathinone (or "cat"), which is derived from khat alkaloids. Only the fresh khat leaves are pharmacologically active, so for some time use was limited to local areas that grew the plant. However, with air transportation, use has spread with emigrants in Europe and the United States. Because of its pharmacological similarities to amphetamine and its addictive properties, khat has been listed on Schedule I of the United Nations Convention on Psychotropic Substances. 

Rose described the toxicity of the senecio plant in 1972 [24]. It is the most common plant species to contain the pyrolizidine alkaloids. Toxicity includes hepatic necrosis and later intrahepatic veno-occlusion. A major secondary component is ATN. There are over 50 species of senecio plants in the south east of South Africa. The plants are used extensively as enemas and purgatives. Rose mentions that, despite the deaths resulting from the use of these plants, the local inhabitants are not aware of the danger these plants pose to their well-being. 

Many observations have been made upon the effect of locality on the production of alkaloids in plants. As these are mostly incapable of explanation at the present time, and of doubtful validity, only a few characteristic examples are given below. Differences of strain, soil, and climate may all come into the question, but it is rarely that any attempt has been made to evaluate their contributory effects. 

As part of our studies on pharmaceutically important alkaloids in C. roseus and Cinchona spp. several aspects of their bios5mthesis were chciracterized and a number of enzymes were purified [4]. In the accumulation of alkaloids in suspension cultured C. roseus cells, it was found that the supply of isoprenoid precursors was a limiting factor. This prompted us to fiarther studies, thereby focusing on the early steps of the isoprenoid biosynthesis (fig. 2). Little was known of these enzymes from plants and except for HMG-CoA reductase, none of the enzymes was characterized [5,6]. Furthermore, there exists much controversy on the subcellular localization of this pathway [7,8]. 

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