The interaction of  -chlorohydrin with glycerol kinase

De, Brooks

doi:10.1530/jrf.0.0560593

Cited by 10 publications

(5 citation statements)

References 26 publications

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“…Enzyme studies showed that purified glycerol kinase (from Candida mycoderma) and ram spermatozoa subjected to ultrasonic vibration could convert cc-chlorohydrin to the phosphorylated derivative (Brooks 1979a); however, it was later shown that the cc-chlorohydrin used in these experiments was contaminated with glycerol (Brooks 1979b). When the glycerol was removed by repeated distillation, the pure cc-chlorohydrin was shown not to be a substrate for the purified enzyme (Brooks 1979b;Jones et al 1981). Metabolic studies with cc-[ 36 CI]chlorohydrin failed to detect its conversion to the phosphorylated derivative by rat or boar sperm (Hutton et al 1980;Jones et al 1981) but did show that biotransformation was occurring.…”

Section: The Active Metabolite Of (X-chlorohydrinmentioning

confidence: 99%

Antifertility Actions of a-Chlorohydrin in the Male

Ar¹

1983

Aust. Jnl. Of Bio. Sci.

109

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Non-steroidal chemicals that affect male fertility have been known for over 25 years but only one compound, alpha-chlorohydrin, possesses most of the attributes of an ideal male contraceptive. In the male rat, for example, continuous daily oral administration of low doses produces an almost immediate and continuous antifertility response that ceases when treatment is withdrawn. Such a dose regime does not interfere with libido, is apparently not toxic and the action is specific towards mature sperm. Furthermore, the action of the compound is species-specific: it is effective in the rat, ram, boar, guinea pig, hamster, rhesus monkey and upon ejaculated human sperm but it is ineffective in the mouse and the rabbit. High doses of alpha-chlorohydrin can be neurotoxic, nephrotoxic and, in rats, lead to prolonged or permanent infertility. However, the antifertility response and the toxicity of racemic alpha-chlorohydrin may be due, respectively, to the separate enantiomers. No other antifertility chemical has been investigated to such an extent as alpha-chlorohydrin; this article reviews the progress that has been achieved with alpha-chlorohydrin during the past six years.

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Section: The Active Metabolite Of (X-chlorohydrinmentioning

confidence: 99%

Antifertility Actions of a-Chlorohydrin in the Male

Ar¹

1983

Aust. Jnl. Of Bio. Sci.

109

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“…It was further suggested, with no substantiating evidence, that this metabolite was cx-chlorohydrin-l-phosphate (3-chloropropan-l,2-diol-l-phosphate), formed by reaction of cx-chlorohydrin with glycerol kinase (EC 2.7.1.30) . Although an early report stated that cx-chlorohydrin was a substrate for glycerol kinase (Thorner 1972), subsequent studies using purified, glycerol-free (R,S)-cx-chlorohydrin showed that this was incorrect (Brooks 1979;Jones et al 1981). Investigations into the metabolism of (R,S)-[3-36 CI]-cx-chlorohydrin by boar spermatozoa did not reveal the formation of cx-chlorohydrin-l-phosphate but did show that the compound underwent oxidation to 3-chlorolactaldehyde of unspecified configuration (Jones et al 1981).…”

Section: Discussionmentioning

confidence: 99%

Inhibition of Fructolysis in Boar Spermatozoa by the Male Antifertility Agent (S)-a-Chlorohydrin

Stevenson¹,

Jones²

1982

Aust. Jnl. Of Bio. Sci.

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The (S)-isomer of the male antifertility agent IX-chlorohydrin strongly inhibited the oxidative metabolism of fructose by boar spermatozoa in vitro. The result of this action, which has been deduced to be an inhibition of glyceraldehydephosphate dehydrogenase, caused an accumulation of fructose-1,6-bisphosphate and the triosephosphates, and a decrease in substrate-level phosphorylation with a concomitant lowering of the energy charge potential of the spermatozoa. The (R)-isomer of IX-chlorohydrin had no inhibitory activity on fructolysis.A study of the comparative metabolism of (R)-[3-36CI]-IX-chlorohydrin and (R,S)-[3-36Cl]_IX_ chlorohydrin by boar spermatozoa showed that it is the (S)-isomer that specifically undergoes a process of oxidative metabolism to (R)-3-chlorolactaldehyde.It is proposed that this endogenous oxidation product, which has the same absolute configuration as the substrate for glyceraldehydephosphate dehydrogenase, is the active metabolite of (S)-IX-chlorohydrin that inhibits this enzyme. Exogenous (R,S)-3-chlorolactaIdehyde inhibited the oxidative metabolism of fructose by boar spermatozoa, apparently by a mechanism similar to that of (S)-IX-chlorohydrin.

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“…Rat spermatozoa therefore have the potential to utilize glycerol as an energy substrate. The inability of exogenous glycerol to stimulate oxygen uptake of rat spermatozoa was surprising, since epididymal spermatozoa from the ram, which contain less glycerol kinase (0-2 units/109 cells: Brooks, 1979d), are stimulated by about 40% by 0-4 mM-glycerol (Edwards et al, 1976). However, the lack of effect of glycerol on the respiration of rat spermatozoa has been demonstrated before (Schenkman et al, 1965) and may be related to the fragility of spermatozoa from the rat (Paz, Kaplan, Yedwab, Homonnai & Kraicer, 1978).…”

Section: Discussionmentioning

confidence: 99%

“…Frozen sperm cells were thawed, sonicated (75 W for 4 15 sec) and assayed for glycerol kinase activity as described by Brooks (1979d). Glycerol kinase activity was expressed as units per 109 spermatozoa, where 1 unit corresponds to 1 pmol glycerol phosphorylated per min at 25°C.…”

Section: Introductionmentioning

confidence: 99%

Entry of glycerol into the rat epididymis and its utilization by epididymal spermatozoa

Cooper¹,

Brooks²

1981

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The availability of glycerol in the epididymal lumen, and the extent of its utilization by spermatozoa, was studied by measurement of the substrate concentration in epididymal fluid and its oxidation in vitro. The source of luminal glycerol was sought by examining its penetration through the epididymal epithelium of a sperm-free tubule by the technique of luminal perfusion during intravenous infusion of glycerol. [3H]Glycerol was rapidly metabolized to a volatile and mobile molecule that quickly equilibrated between blood plasma and the epididymal lumen and so could not be used to monitor transfer. When blood levels of glycerol were raised by infusion of large amounts of the unlabelled compound, glycerol was detected in epididymal perfusates and a positive linear correlation existed between the rate of secretion into the epididymal lumen and the blood plasma concentration, suggesting that passive diffusion across the epithelium from blood could occur. In normal rats, however, the concentration of glycerol in sperm-free epididymal fluid (1.15 mM) exceeded that in blood plasma (0.35 mM). Luminal glycerol is therefore thought to arise from degradation of epididymal lipid.

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The interaction of -chlorohydrin with glycerol kinase

Cited by 10 publications

References 26 publications

Antifertility Actions of a-Chlorohydrin in the Male

Antifertility Actions of a-Chlorohydrin in the Male

Inhibition of Fructolysis in Boar Spermatozoa by the Male Antifertility Agent (S)-a-Chlorohydrin

Entry of glycerol into the rat epididymis and its utilization by epididymal spermatozoa

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