Inhibitory effects of (S)-3-chlorolactaldehyde on the metabolic activity of boar spermatozoa in vitro

Abstract

(S)-alpha-Chlorohydrin and 3-chloro-1-hydroxyacetone inhibited the oxidative metabolism of fructose by boar spermatozoa only after a period of incubation in which they presumably underwent conversion to (S)-3-chlorolactaldehyde, an inhibitor of sperm glyceraldehyde 3-phosphate dehydrogenase. With glycerol as substrate, 3-chloro-1-hydroxyacetone had a similar effect, (S)-alpha-chlorohydrin was ineffective while (R,S)-3-chlorolactaldehyde was immediately effective with either substrate. All three compounds caused the accumulation of fructose 1,6-bisphosphate and dihydroxyacetone phosphate from fructose but not from glycerol which led to the conclusion that inhibition of triosephosphate isomerase was also associated with the anti-glycolytic action of (S)-3-chlorolactaldehyde. (S)-3-Chlorolactaldehyde caused the depletion of ATP in incubates of boar spermatozoa metabolizing fructose but not glycerol. This suggests that futile substrate cycling may play an important function in the anti-glycolytic action of (S)-3-chlorolactaldehyde and/or that boar spermatozoa can synthesize ATP from glycerol by a mechanism not involving the glycolytic pathway.

Spermatotoxic effects of α-chlorohydrin in rats

“…The inhibitory effect of ACH on metabolic activity of sperm in vitro is thought to occur via ACH oxidation within the sperm to form 3-chlorolctaldehyde, which then inhibits GAPDH [24]. GAPDH, a glycolytic enzyme, is known as a major target protein in oxidative stress [25] and is an important key enzyme to generation of ATP which is necessary for sperm motility and male fertility [26].…”

Glyceraldehyde 3-phosphate dehydrogenase-S protein distribution during mouse spermatogenesis

“…These compounds are converted to the common metabolite (S)-3-chlorolactaldehyde, a competitive substrate inhibitor of the GAPD isoform in sperm that reduces fertility in several mammalian species [6,[26][27][28][29][30][31]. Infertility mediated by (S)-3-chlorolactaldehyde is associated with reduced motility and reduced enzymatic activity in sperm, at concentrations that do not inhibit activity of the GAPD isoform in somatic tissues [32].…”

Glycerol 3-phosphate dehydrogenase of boar spermatozoa: inhibition by -bromohydrin phosphate

“…1) is oxidized within the spermatozoa of susceptible species to (S)-3-chlorolactaldehyde (II in Fig. 1) which inhibits the activities of triosephosphate isomerase and glyceraldehyde 3-phosphate dehydrogenase, thereby preventing the cells from synthesizing ATP which is essential for the maintenance of motility (Cooney and Jones, 1988). Early biochemical studies with the racemate, (R,S)-achlorohydrin, led to the proposal that the active metabolite was the phosphorylated derivative, a-chlorohydrin-1-phosphate (III in Fig.…”

“…3. Effect of a-bromohydrin phosphate on the concentration of (a) dihydroxyacetone phosphate (DHAP) (n = 8) and (b) fructose-1,6-bisphosphate (F-l,6-P2) ( Cooney, 1987, Cooney andJones, 1988), or 3-bromopyruvate, which inhibits glyceraldehyde 3-phosphate dehydrogenase and 3-phosphoglycerate kinase , also prevented the production of C02, resulted in an increase in concen¬ trations of dihydroxyacetone phosphate and fructose-1,6-bisphosphate, but had no appreciable effect on the (Voet and Voet, 1995); the former is located in the cytoplasm whereas the latter is bound to the inner mitochondrial membrane (Klingenberg and Bucholz, 1970 These results confirm those of Ford (1981) that, in boar spermatozoa, glycerol 3-phosphate is oxidized primarily by an FAD-dependent dehydrogenase that is probably extrinsically bound to the inner mitochondrial membrane (Klingenberg and Bucholz, 1970). In this respect, boar spermatozoa are similar to those of rams (Ford, 1981), rats (Ford, 1981;Brooks, 1978;Schenkman et al, 1965) and cocks (Yamada and Terada, 1974) but not those of mice (Burgos et al, 1982) or humans (Ford, 1981).…”