D-BETA-HYDROXYBUTYRATE AND L-BETA-HYDROXYBUTYRATE DEHYDROGENASES AND THE EVOLUTION OF KETONE-BODY METABOLISM IN GASTROPOD MOLLUSKS

In vertebrate animals, ketone bodies, synthesized primarily from store d lipid, are important metabolic substrates (1). During starvation, ke tone bodies, acetoacetate (Acac) and beta-hydroxybutyrate (BHB), are o xidized by some extrahepatic tissues at high rates, and thus perform t he important function of sparing limited glycogen stores (1, 2). The e nzyme beta-hydroxybutyrate dehydrogenase (BHBDH), which catalyzes the interconversion of the ketone bodies, is found in all mammals and most vertebrates, but is absent in most Invertebrates (1, 3), including ma rine molluscs (4). The highest measured BHBDH activities in the animal kingdom, however are found in the hearts of terrestrial gastropod mol luscs (5 6). We have recently demonstrated that, in tissues of the ter restrial gastropod Cepaea nemoralis, two unique and previously unknown isoforms of BHBDH occur (5). The isoforms differ from the well-charac terized mitochondrial membrane-bound D-BHBDH found in all other animal s (7) in that they are cytosolic, and one isoform is specific for the L-enantiomer of BHB. Here we identify patterns in the evolution of the se enzyme isoforms in the Gastropoda. BHBDH activities, stereospecific ity and subcellular compartmentalization were measured in gastropod sp ecies representing four major groups with freshwater and terrestrial r epresentation: Neritomorpha (primitive gilled gastropods), Architaenio glossa (more advanced gilled gastropods), Basommatophora (freshwater p ulmonates), and Stylommatophora (terrestrial pulmonates). Mapping of t hese data onto a phylogeny of the Gastropoda (8) indicates that cytoso lic D- and L-BHBDH have arisen a single time, in an ancestral stylomma tophoran. All gastropods of the order Stylommatophora possess this uni que organization of ketone body metabolism, which has not been found e lsewhere in the animal kingdom.