Mode of Action of Hypoglycin and Related Compounds

Abstract

The ackee, Blighia sapida, was introduced to the West Indies from West Africa about 190 years ago. The fleshy arillus of its fruit is often eaten in Jamaica, but if unripe these occasionally cause ‘vomiting sickness’ characterized by severe hypoglycaemia and sometimes death. The toxic principle is an unusual amino-acid, hypoglycin (l-2-amino-3-methylene-cyclopropylpropionic acid) (Table 1). Several related compounds are also hypoglycaemic: a methylene group separated by two carbon atoms from a carboxyl group (or a potential carboxyl group which is exposed after metabolism) seems necessary for activity in this series of compounds (Table 1). Of these, hypoglycin, its metabolite methylenecyclopropylacetic acid, and its synthetic analogue pent-4-enoic acid, have been investigated in detail by Bressler, Holt, Sherratt, J. R. Williamson and their co-workers and four structurally similar but non-hypoglycaemic fatty acids (Table 1) have been used as controls by Senior & Sherratt (1968a) to try to find the biochemical effects relevant to hypoglycaemic activity. This field has recently been reviewed by Stewart & Hanley (1968), Bressler et al., (1969) and Sherratt (1969) and these articles should be consulted for further details. Some aspects of this work are discussed here and some recent results are presented.