1. Effect of alpha-chlorohydrin on glucose metabolism by spermatozoa from the cauda epididymidis of the rhesus monkey (Macaca mulatta)
W C Ford, A Harrison J Reprod Fertil. 1980 Sep;60(1):59-64. doi: 10.1530/jrf.0.0600059.
Spermatozoa from the cauda epididymidis of the rhesus monkey had metabolic properties similar to those published for ejaculated spermatozoa. The concentration of glycolytic intermediates was low until 2 mM-glucose was added; glucose 6-phosphate, fructose 1,6-bis-phosphate and the triose plhosphates then increased but glycerate 3-phosphate did not. It was concluded that the activity of glyceraldehyde 3-phosphate dehydrogenase (EC 1.2.1.12) limited flux through the glycolytic pathway. The production of lactate and CO2 from glucose was strongly inhibited in the presence of 5 or 10 mM-alpha-chlorohydrin. The energy charge of the spermatozoa was low before and after 1 incubation with 2 mM-glucose (0.5 +/- 0.05 and 0.05 +/- 0.06 respectively) and the value after the incubation was decreased in the presence of 5 or 10 mM-alpha-chlorohydrin (0.17 +/- 0.05 and 0.15 +/- 0.04 respectively). alpha-Chlorohydrin inhibited glycolysis at the glyceraldehyde 3-phosphate dehydrogenase reaction.
2. The action of (S)-alpha-chlorohydrin and 6-chloro-6-deoxyglucose on the metabolism of guinea pig spermatozoa
A R Jones, S A Ford Contraception. 1984 Sep;30(3):261-9. doi: 10.1016/0010-7824(84)90089-1.
(S)-alpha-Chlorohydrin inhibits the conversion of fructose to lactate by mature guinea pig spermatozoa in vitro. At a concentration of 2mM, there is a specific inhibition of glyceraldehyde-phosphate dehydrogenase resulting in the accumulation of fructose-1,6-bisphosphate, dihydroxyacetone phosphate and glyceraldehyde-3-phosphate and a concomitant decrease in the concentration of endogenous lactate. (R,S)-[3-36Cl]-alpha-Chlorohydrin is metabolised by the spermatozoa to 3-chlorolactaldehyde of unknown configuration. Exogenous (R,S)-3-chlorolactaldehyde (2mM) is an inhibitor of glyceraldehyde-phosphate dehydrogenase in guinea pig spermatozoa, whereas (R)-alpha-chlorohydrin (10mM) has no significant effect on the metabolism of fructose. 6-Chloro-6-deoxyglucose (10mM) inhibits glyceraldehyde-phosphate dehydrogenase in guinea pig spermatozoa in vitro and is metabolised to 3-chlorolactaldehyde which is presumably the (S)-isomer. The anti-glycolytic actions of (S)-alpha-chlorohydrin and 6-chloro-6-deoxyglucose in guinea pig spermatozoa are suggested to be due to the action of a common metabolite, (S)-3-chlorolactaldehyde.
3. Inhibition of glycolysis in boar sperm by alpha-chlorohydrin
P Hutton, A G Dawson, A R Jones Contraception. 1980 Nov;22(5):505-12. doi: 10.1016/0010-7824(80)90103-1.
The effect of alpha-chlorohydrin (3-chloropropan-1,2-diol) on the metabolism of D-[U-14C]-fructose and L-[U-14C]-lactate by washed boar sperm has been investigated. Whereas alpha-chlorohydrin at concentrations as low as 0.1 mM inhibited the metabolism of fructose and led to an increase in the utilization of endogenous lactate, amounts up to 500 mM had no effect on the oxidation of added lactate. Low levels of alpha-chlorohydrin increased the cellular concentrations of fructose-1,6-bisphosphate and the triosephosphates, an effect consistent with the inhibition of glyceraldehyde-3-phosphate dehydrogenase. Although [U-14C]-glycerol was rapidly oxidized by boar sperm, [U-14C]-alpha-chlorohydrin was not metabolized to 14CO2, showing that it is not converted to glycerol. Extracts obtained by sonication of boar sperm after incubation with [3-36C1]-alpha-chlorohydrin, did not contain [3-36C1]-alpha-chlorohydrin-1-phosphate. This is contrary to the postulate that this phosphorylated compound is the inhibitory metabolite of alpha-chlorohydrin.
