Abstract
BackgroundThe L-lactate and D-lactate dehydrogenases, which are involved in the reduction of pyruvate to L(-)-lactate and D(+)-lactate, belong to evolutionarily unrelated enzyme families. The genes encoding L-LDH have been used as a model for gene duplication due to the multiple paralogs found in eubacteria, archaebacteria, and eukaryotes. Phylogenetic studies have suggested that several gene duplication events led to the main isozymes of this gene family in chordates, but little is known about the evolution of L-Ldh in invertebrates. While most invertebrates preferentially oxidize L-lactic acid, several species of mollusks, a few arthropods and polychaetes were found to have exclusively D-LDH enzymatic activity. Therefore, it has been suggested that L-LDH and D-LDH are mutually exclusive. However, recent characterization of putative mammalian D-LDH with significant similarity to yeast proteins showing D-LDH activity suggests that at least mammals have the two naturally occurring forms of LDH specific to L- and D-lactate. This study describes the phylogenetic relationships of invertebrate L-LDH and D-LDH with special emphasis on crustaceans, and discusses gene duplication events during the evolution of L-Ldh.ResultsOur phylogenetic analyses of L-LDH in vertebrates are consistent with the general view that the main isozymes (LDH-A, LDH-B and LDH-C) evolved through a series of gene duplications after the vertebrates diverged from tunicates. We report several gene duplication events in the crustacean, Daphnia pulex, and the leech, Helobdella robusta. Several amino acid sequences with strong similarity to putative mammalian D-LDH and to yeast DLD1 with D-LDH activity were found in both vertebrates and invertebrates.ConclusionThe presence of both L-Ldh and D-Ldh genes in several chordates and invertebrates suggests that the two enzymatic forms are not necessarily mutually exclusive. Although, the evolution of L-Ldh has been punctuated by multiple events of gene duplication in both vertebrates and invertebrates, a shared evolutionary history of this gene in the two groups is apparent. Moreover, the high degree of sequence similarity among D-LDH amino acid sequences suggests that they share a common evolutionary history.
Highlights
The L-lactate and D-lactate dehydrogenases, which are involved in the reduction of pyruvate to L(-)-lactate and D(+)-lactate, belong to evolutionarily unrelated enzyme families
Studies on the primary amino acid structures of L-LDH and D-lactate dehydrogenases (D-LDH) suggest that the genes encoding them are not evolutionarily related [2,3] and that their products belong to larger families of enzymes: L(-)-LDHs belong to the L-specific NAD-dependent dehydrogenases, while D(+)-LDHs belong to the D-isomer specific 2-hydroxy acid dehydrogenases and the FAD-binding oxidoreductase/transferase type 4 family
It will be interesting to determine whether the "missing" enzyme in such cases is the result of gene inactivation, degradation into a pseudogene, deletion, or is expressed at such low levels that the enzyme is not detected in typical assays. The presence of both L-Ldh and D-Ldh in several chordates and invertebrates suggests that the two enzymatic forms are not necessarily mutually exclusive
Summary
The L-lactate and D-lactate dehydrogenases, which are involved in the reduction of pyruvate to L(-)-lactate and D(+)-lactate, belong to evolutionarily unrelated enzyme families. Phylogenetic studies have suggested that several gene duplication events led to the main isozymes of this gene family in chordates, but little is known about the evolution of L-Ldh in invertebrates. This study describes the phylogenetic relationships of invertebrate L-LDH and D-LDH with special emphasis on crustaceans, and discusses gene duplication events during the evolution of L-Ldh. The reduction of pyruvate to L(-)-lactate and D(+)-lactate is catalyzed by different NAD-dependent enzymes, the Llactate (L-LDH: L-lactate:NAD+ oxidoreductase, EC 1.1.1.27) and D-lactate dehydrogenases (D-LDH: D-lactate:NAD+ oxidoreductase, EC 1.1.1.28) as well as by NAD-independent (cytochrome) enzymes (DLD: D-lactate ferricytochrome c oxidoreductase, EC 1.1.2.4). The reduction of pyruvate to L(-)-lactate and D(+)-lactate is catalyzed by different NAD-dependent enzymes, the Llactate (L-LDH: L-lactate:NAD+ oxidoreductase, EC 1.1.1.27) and D-lactate dehydrogenases (D-LDH: D-lactate:NAD+ oxidoreductase, EC 1.1.1.28) as well as by NAD-independent (cytochrome) enzymes (DLD: D-lactate ferricytochrome c oxidoreductase, EC 1.1.2.4) Despite their apparent functional similarity, these classes of enzymes are selective for the D/L chirality of the substrate [1]. The recent description of mammalian D-LDH enzymes that show significant similarity to yeast proteins with D-LDH activity [5] prompted our search for sequences with putative D-LDH activity in both vertebrate and invertebrate genomes
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