Epitopes of human testis-specific lactate dehydrogenase deduced from a cDNA sequence.

All vertebrates other than lampreys exhibit multiple loci encoding lactate dehydrogenase +ADL-LDH; (S)-lactate:NAD+ oxidoreductase, EC 1.1.1.27+BD. Of these loci, Ldh-A is expressed predominantly in muscle, Ldh-B is expressed predominantly in heart, and Ldh-C (where present) exhibits different tissue-restricted patterns of expression depending on the taxon. To examine the relationship of the single LDH of lampreys to other vertebrate LDHs, we have determined the cDNA sequence of the LDH of the sea lamprey Petromyzon marinus and compared it to previously published sequences from bacteria, plants, and vertebrates. The lamprey sequence exhibits a mixture of features of both LDH-A and LDH-B at the amino acid level that may account for its intermediate kinetic properties. Both distance and maximum parsimony analyses strongly reject a relationship of lamprey LDH with mammalian LDH-C but do not significantly distinguish among remaining alternative phylogenetic hypotheses. Evolutionary parsimony analyses suggest that the lamprey LDH is related to Ldh-A and that the single locus condition has arisen as a result of the loss of Ldh-B (prior to the appearance of Ldh-C). The collection of LDH sequences for further studies of the evolution of the vertebrate LDH gene family will be facilitated by the PCR approach that we have used to obtain the lamprey sequence.

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Evolutionary implications of the cDNA sequence of the single lactate dehydrogenase of a lamprey.

Stock

Whitt

1992

“…Phylogenetic analyses of amino acid sequences revealed that the mammalian testis-specific LDH-C subunit diverged prior to the split ofthe LDH-A and LDH-B subunits (4)(5)(6). A third possibility has also been suggested (7,8), that the mammalian LDH-C gene originated from a duplication of the LDH-A gene after the A-B duplication. As a separate matter, the teleost LDH-C gene is derived from a duplication of the LDH-B gene (9).…”

mentioning

confidence: 99%

Evolutionary relationships of lactate dehydrogenases (LDHs) from mammals, birds, an amphibian, fish, barley, and bacteria: LDH cDNA sequences from Xenopus, pig, and rat.

Tsuji

Qureshi

Hou

et al. 1994

The nucleotide sequences of the cDNAs encoding LDH (EC 1.1.1.27) subunits LDH-A (muscle), LDH-B (liver), and LDH-C (oocyte) from Xenopus laevis, LDH-A (muscle) and LDH-B (heart) from pig, and LDH-B (heart) and LDH-C (testis) from rat were determined. These seven newly deduced amino acid sequences and 22 other published LDH sequences, and three unpublished fish LDH-A sequences kindly provided by G. N. Somero and D. A. Powers, were used to construct the most parsimonious phylogenetic tree of these 32 LDH subunits from mammals, birds, an amphibian, fish, barley, and bacteria. There have been at least six LDH gene duplications among the vertebrates. The Xenopus LDH-A, LDH-B, and LDH-C subunits are most closely related to each other and then are more closely related to vertebrate LDH-B than LDH-A. Three fish LDH-As, as well as a single LDH of lamprey, also seem to be more related to vertebrate LDH-B than to land vertebrate LDH-A. The mammalian LDH-C (testis) subunit appears to have diverged very early, prior to the divergence of vertebrate LDH-A and LDH-B subunits, as reported previously.

“…Several glycolytic enzymes in mammalian sperm are distinct from the isozymes present in somatic tissues. Three isozymes, glyceraldehyde 3-phosphate dehydrogenase-S (GAPDS), phosphoglycerate kinase-2, and lactate dehydrogenase-C 4 , are encoded by paralogous genes expressed only during spermatogenesis (5,(9)(10)(11)(12)(13). At least five other enzymes in the glycolytic pathway have unique structural or functional properties in spermatogenic cells (6,(14)(15)(16)(17)(18).…”

mentioning

confidence: 99%

Glyceraldehyde 3-phosphate dehydrogenase-S, a sperm-specific glycolytic enzyme, is required for sperm motility and male fertility

Miki

Goulding

et al. 2004

549

457

Although glycolysis is highly conserved, it is remarkable that several unique isozymes in this central metabolic pathway are found in mammalian sperm. Glyceraldehyde 3-phosphate dehydrogenase-S (GAPDS) is the product of a mouse gene expressed only during spermatogenesis and, like its human ortholog (GAPD2), is the sole GAPDH isozyme in sperm. It is tightly bound to the fibrous sheath, a cytoskeletal structure that extends most of the length of the sperm flagellum. We disrupted Gapds expression by gene targeting to selectively block sperm glycolysis and assess its relative importance for in vivo sperm function. Gapds ؊/؊ males were infertile and had profound defects in sperm motility, exhibiting sluggish movement without forward progression. Although mitochondrial oxygen consumption was unchanged, sperm from Gapds ؊/؊ mice had ATP levels that were only 10.4% of those in sperm from WT mice. These results imply that most of the energy required for sperm motility is generated by glycolysis rather than oxidative phosphorylation. Furthermore, the critical role of glycolysis in sperm and its dependence on this sperm-specific enzyme suggest that GAPDS is a potential contraceptive target, and that mutations or environmental agents that disrupt its activity could lead to male infertility. glycolysis ͉ gene targeting ͉ infertility S perm motility is essential for normal fertilization, and asthenozoospermia, or low sperm motility, is common in infertile men. In a recent study of 1,085 sperm samples from infertile men, 81% had defects in motility, and 19% had asthenozoospermia without other defects in sperm number or morphology (1). Motility is generated by the extremely long flagellum that comprises Ͼ90% of the length of a mammalian sperm. This process requires substantial ATP to support coordinated movement of the central axoneme and surrounding flagellar structures (2). ATP is hydrolyzed by dynein ATPases, which function as force-generating molecular motors along the axoneme. Although quiescent in the epididymis, mammalian sperm display vigorous forward movement, termed activated or progressive motility, immediately upon ejaculation or collection into physiological medium. The motility waveform changes in the female reproductive tract, with increases in both the amplitude and asymmetry of flagellar bending. These changes result in a whiplash-like motion, termed hyperactivated motility, which facilitates sperm transport in the oviduct and penetration of the zona pellucida surrounding the oocyte (3).Potential sources of ATP to support sperm motility are compartmentalized in distinct regions along the length of the flagellum. Oxidative phosphorylation is confined to the proximal segment of the flagellum where the mitochondria are localized (middle piece). In contrast, glycolysis appears to be restricted to the principal piece, which is distal to the middle piece and is the longest segment of the sperm flagellum (4-8). Several glycolytic enzymes in mammalian sperm are distinct from the isozymes present in somatic tissues. Thr...