The concerted effect of  -chlorohydrin and glucose on the ATP concentration in spermatozoa is associated with the accumulation of glycolytic intermediates

Ford, W. C. L.; Harrison, Anne

doi:10.1530/jrf.0.0770537

Cited by 17 publications

(10 citation statements)

References 10 publications

(9 reference statements)

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“…When BHB was supplemented to the sperm suspension instead of glucose, the percentage of sperm motility was not affected by α-chlorohydrin (ACH), a potent inhibitor of GAPDH. Moreover, it was reported that intracellular ATP concentration was not decreased by ACH in the absence of glucose (Ford and Harrison, 1985;Ford and Harrison, 1986). These results support that respiration is enough to supply ATP for sperm motility.…”

Section: Introductionsupporting

confidence: 63%

Glycolysis plays an important role in energy transfer from the base to the distal end of the flagellum in mouse sperm

Takei

Miyashiro

Mukai

et al. 2014

Journal of Experimental Biology

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Many studies have been conducted to elucidate the relationship between energy metabolic pathways (glycolysis and respiration) and flagellar motility in mammalian sperm, but the contribution of glycolysis to sperm motility has not yet been fully elucidated. In the present study, we performed detailed analysis of mouse sperm flagellar motility for further understanding of the contribution of glycolysis to mammalian sperm motility. Mouse sperm maintained vigorous motility in the presence of substrates either for glycolysis or for respiration. By contrast, inhibition of glycolysis by alphachlorohydrine caused a significant decrease in the bend angle of the flagellar bending wave, sliding velocity of outer doublet microtubules and ATP content even in the presence of respiratory substrates (pyruvate or β-hydroxybutyrate). The decrease of flagellar bend angle and sliding velocity are prominent in the distal part of the flagellum, indicating that glycolysis inhibition caused the decrease in ATP concentration threrein. These results suggest that glycolysis potentially acts as a spatial ATP buffering system, transferring energy (ATP) synthesized by respiration at the mitochondria located in the basal part of the flagellum to the distal part. In order to validate that glycolytic enzymes can transfer high energy phosphoryls, we calculated intraflagellar concentration profiles of adenine nucleotides along the flagellum by computer simulation analysis. The result demonstrated the involvement of glycolysis for maintaining the ATP concentration at the tip of the flagellum. It is likely that glycolysis plays a key role in energy homeostasis in mouse sperm not only through ATP production but also through energy transfer.

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Section: Introductionsupporting

confidence: 63%

Glycolysis plays an important role in energy transfer from the base to the distal end of the flagellum in mouse sperm

Takei

Miyashiro

Mukai

et al. 2014

Journal of Experimental Biology

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“…Previous studies have shown ACH affected sperm GAPDS activity or ATP levels [22], [58]–[59]. In this study, on only GAPDS activity and ATP levels, but also cAMP levels, P-PKAs and PTP significantly decreased while rat sperm were exposed to SACH.…”

Section: Discussionsupporting

confidence: 44%

(S)-α-Chlorohydrin Inhibits Protein Tyrosine Phosphorylation through Blocking Cyclic AMP - Protein Kinase A Pathway in Spermatozoa

Zhang

Wang

et al. 2012

PLoS ONE

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α-Chlorohydrin is a common contaminant in food. Its (S)-isomer, (S)-α-chlorohydrin (SACH), is known for causing infertility in animals by inhibiting glycolysis of spermatozoa. The aim of present work was to examine the relationship between SACH and protein tyrosine phosphorylation (PTP), which plays a critical role in regulating mammalian sperm capacitation. In vitro exposure of SACH 50 µM to isolated rat epididymal sperm inhibited PTP. Sperm-specific glyceraldehyde 3-phosphate dehydrogenase (GAPDS) activities, the intracellular adenosine 5′-triphosphate (ATP) levels, 3′-5′-cyclic adenosine monophosphate (cAMP) levels and phosphorylation of protein kinase A (PKA) substrates in rat sperm were diminished dramatically, indicating that both glycolysis and the cAMP/PKA signaling pathway were impaired by SACH. The inhibition of both PTP and phosphorylation of PKA substrates by SACH could be restored by addition of cAMP analog dibutyryl-cAMP (dbcAMP) and phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (IBMX). Moreover, addition of glycerol protected glycolysis, ATP levels, phosphorylation of PKA substrates and PTP against the influence of SACH. These results suggested SACH inhibited PTP through blocking cAMP/PKA pathway in sperm, and PTP inhibition may play a role in infertility associated with SACH.

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“…Incubations. These were done in 10-ml conical flasks in a shaking water bath at 34°C with air as the gas phase and were organized in a similar way to previous experiments (Ford et ai, 1981;Ford & Harrison, 1986). The incubation period with a-chlorohydrin before the addition of substate was 10 min for boar and 30 min for rat spermatozoa.…”

Section: Methodsmentioning

confidence: 99%

“…Under a variety ofconditions the decrease in ATP was always accompanied by a concomitant increase in the concentration of fructose 1,6-bisphosphate. Fructose 1,6-bisphosphate never accumulated when there was no decline in ATP (Ford & Harrison, 1986).…”

Section: Introductionmentioning

confidence: 94%

Futile substrate cycles in the glycolytic pathway of boar and rat spermatozoa and the effect of -chlorohydrin

Ford¹,

Harrison²

1987

Reproduction

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In boar spermatozoa incubated with 0.1 mM-glucose about 20 nmol glucose were converted to lactate and CO2 and the rate of futile substrate cycling between glucose and glucose 6-phosphate was about 6 nmol/10(8) spermatozoa/30 min. Futile cycling was increased in the presence of 0.05 or 1 mM-alpha-chlorohydrin but not to an extent sufficient to account for the rapid decline in ATP concentration observed under these conditions. These estimates include a substantial rate of fructose formation from fructose phosphates. The addition of 10 mM-L-lactate plus 1 mM-pyruvate protected the spermatozoa against the effect of alpha-chlorohydrin and glucose on the ATP concentration but increased futile substrate cycling. Substrate cycling between fructose 6-phosphate and fructose 1,6-bisphosphate could not be measured in boar spermatozoa but in rat spermatozoa its rate (nmol/10(8) spermatozoa/30 min) was about 10 under control condition and about 25 in the presence of 1 mM-alpha-chlorohydrin. This increase was insufficient to account for the decline in ATP concentration. In both species futile substrate cycling consumed a significant proportion of the ATP synthesis during lactate production but only about 5% of that produced in the oxidation of glucose to acetyl carnitine and CO2.

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The concerted effect of -chlorohydrin and glucose on the ATP concentration in spermatozoa is associated with the accumulation of glycolytic intermediates

Cited by 17 publications

References 10 publications

Glycolysis plays an important role in energy transfer from the base to the distal end of the flagellum in mouse sperm

Glycolysis plays an important role in energy transfer from the base to the distal end of the flagellum in mouse sperm

(S)-α-Chlorohydrin Inhibits Protein Tyrosine Phosphorylation through Blocking Cyclic AMP - Protein Kinase A Pathway in Spermatozoa

Futile substrate cycles in the glycolytic pathway of boar and rat spermatozoa and the effect of -chlorohydrin

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