The DOI matches its Crossref record; 28 of the 28 references it cites were found in a registry or an index.
Glyceraldehyde 3-phosphate dehydrogenase-S, a sperm-specific glycolytic enzyme, is required for sperm motility and male fertility
Open accessAbstract
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.
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Cites
Targeted disruption of the c-src proto-oncogene leads to osteopetrosis in mice
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Self-citationHuman testis-specific PGK gene lacks introns and possesses characteristics of a processed gene
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Targeted Disruption of the Akap4 Gene Causes Defects in Sperm Flagellum and Motility
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Cited by
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The facilitative glucose transporter GLUT3: 20 years of distinction
Simpson, I. A., Dwyer, D., Malide, D., Moley, K. H., Travis, A., & Vannucci, S. J. (2008) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.90388.2008 · Cited by 473
The role of mitochondria in energy production for human sperm motility
Piomboni, P., Focarelli, R., Stendardi, A., Ferramosca, A., & Zara, V. (2012) · International Journal of Andrology · doi:10.1111/j.1365-2605.2011.01218.x · Cited by 458
Sirover, M. A. (2011) · Biochimica et Biophysica Acta (BBA) - General Subjects · doi:10.1016/j.bbagen.2011.05.010 · Cited by 326
Human pyruvate kinase M2: A multifunctional protein
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Metadata
- Authors
- Miki, K., Qu, W., Goulding, E. H., Willis, W. D., Bunch, D. O., Strader, L. F., Perreault, S. D., Eddy, E. M., & O'Brien, D. A.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 2004-11-16
- Volume
- 101
- Issue
- 47
- Pages
- 16501-16506
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W1981905015
- Cited by
- 620
- References
- 28
- FWCI
- 21.98
- Type
- journal article
- Language
- en
- Open access
- green
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- Miki, K., Qu, W., Goulding, E. H., Willis, W. D., Bunch, D. O., Strader, L. F., Perreault, S. D., Eddy, E. M., & O'Brien, D. A. (2004). Glyceraldehyde 3-phosphate dehydrogenase-S, a sperm-specific glycolytic enzyme, is required for sperm motility and male fertility. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.0407708101
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