D- and L-lactate dehydrogenases during invertebrate evolution

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.

Inhibition of Lactate Dehydrogenase Activity as an Approach to Cancer Therapy

“…Enzymes producing d(+)-lactate (d(+)-LDHs) are common in invertebrates, protists and bacteria; studies on the primary amino acid sequence suggested that they are not evolutionarily related with LDHs producing l(-)lactate (l(-)-LDHs) [2]. l(-)-LDHs belong to the l-specific NAD-dependent dehydrogenases, while d(+)-LDHs belong to the d-isomer specific 2-hydroxyacid dehydrogenases and the FAD-binding oxidoreductase family.…”

Bioconversion of Phenylpyruvate to Phenyllactate: Gene Cloning, Expression, and Enzymatic Characterization of d- and l1-Lactate Dehydrogenases from Lactobacillus plantarum SK002

“…Given the low homology of ldhL1 and ldhL2 with ldhD, the two are probably of different evolutionary origin from the ldhD gene as suggested by Taguchi et al [20]. The two ldhL genes were as a result of duplicating events as recently explained by Cristescu et al [21].…”

Imperfect Asymmetry of Life: Earth Microbial Communities Prefer D-Lactate but Can Use L-Lactate Also

“…1), the literature contains many examples of L-lactate bacteria (Garvie, 1980;Traudt and Kleinberg, 1996). Although complex, eukaryotic organisms are less relevant to the astrobiology of Mars, most invertebrates, plants, and animals metabolize only L-lactate (Cristescu, 2008;Passarella et al, 2008). Our knowledge about D-, L-, and DL-lactate users, especially among the domain Archaea, is incomplete and perhaps even inaccurate.…”