Monkey lactate dehydrogenase-C4 as a model for the interaction of enzymes with gossypol

Whaley, Kevin J.; Stephens, Donald T.; Klimkow, Nanette M.; Hoskins, Dale D.

doi:10.1016/0010-7824(86)90049-1

Cited by 9 publications

(4 citation statements)

References 36 publications

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“…Furthermore, in experiments on direct inhibition of LDH-C4 no specific effect of ( -)gossypol was observed. Racemic gossypol and the ( + )-and ( -)-enantiomers of gossypol all showed a direct inhibitory effect on the activity of LDH-C4 (Kim et al, 1985;Whaley et al, 1986). This may indicate that the specific effect of ( -)gossypol on LDH-C4 activity in the present in-vitro system involves a different mechanism of gossypol action.…”

Section: Discussionmentioning

confidence: 46%

“…These include effects on mitochondrial electron transport and oxidative phosphorylation, and inhibition of a number of enzymes involved in energy metabolism (Adeyemo et al, 1982;Tso & Lee, 1982a;Stephens et al, 1983;Kim & Waller, 1984). Much attention has been paid to possible inhibition of the lactate dehydrogenase isoenzyme LDH-C4 Tso & Lee, 1982b;Morris et al, 1986;Whaley et al, 1986). LDH-C4 is composed of male germ cell-specific C subunits (Zinkham, 1968), and inhibition of this isoenzyme would specifically interfere with the metabolism of spermatogenic cells and spermatozoa.…”

Section: Introductionmentioning

confidence: 98%

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Differential effects of (+)- and (-)-gossypol enantiomers on LDH-C4 activity of hamster spermatogenic epithelium in vitro

Boer

Grootegoed²

1988

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Tubular fragments (spermatogenic epithelium) from immature hamsters were isolated and cultured with low doses of (+)- and (-)-gossypol enantiomers. The activity of lactate dehydrogenase isoenzyme LDH-C4 was estimated as a marker for spermatogenic cell development and alpha-ketoisovalerate was used as the substrate. In the absence of gossypol, the specific activity of LDH-C4 in the tubular fragments was increased 40% during incubation for 48 h. This developmental increase was suppressed by gossypol. The specific activity of LDH-C4 in the tubular fragments was lowered by gossypol, after 48 h of culture in the presence of low doses of racemic gossypol (1-4 microM) and 1% fetal calf serum. In this in-vitro system the (-)-enantiomer but not the (+)-enantiomer of gossypol affected the LDH-C4 activity. This is in agreement with other reports showing that only the (-)-enantiomer induces infertility. The observed action of gossypol on LDH-C4 activity in the tubular fragments may reflect gossypol-induced degeneration of spermatogenic cells. The present in-vitro system can be used to estimate the actions of gossypol derivatives, other investigational antifertility agents, and toxic agents on the spermatogenic epithelium.

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Section: Discussionmentioning

confidence: 46%

Section: Introductionmentioning

confidence: 98%

Differential effects of (+)- and (-)-gossypol enantiomers on LDH-C4 activity of hamster spermatogenic epithelium in vitro

Boer

Grootegoed²

1988

Reproduction

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“…The described effect of ( -)gossypol on the ATP content of the spermatids was evaluated in relation to possible effects of gossypol on LDH-C4. The lactate dehydrogenase isoenzyme LDH-C4, which appears to be a key enzyme in the metabolism of the male germ cells, has been proposed as a potential site of action for the antifertility effect of gossypol (Tso & Lee, 1982b;Olgiati & Toscano, 1983;Kim et al, 1985;Whaley et al, 1986). In these studies, crude or purified preparations of LDH-C4 were treated with gossypol which resulted in inhibition of the enzyme.…”

Section: Discussionmentioning

confidence: 99%

“…The inhibition of the glycolytic pathway and the citric acid cycle could result from inhibition of distinct enzymes. More specifically, an effect of gossypol on the activity of testis-and sperm-specific LDH-C4 has been demonstrated (Tso & Lee, 1982b; Higgins & Morris, 1985;Kim et al, 1985;Whaley et al, 1986;Giridharan et al, 1987).…”

Section: Introductionmentioning

confidence: 99%

Mechanism of action of (-)gossypol on ATP production in isolated hamster spermatids

Boer

Grootegoed²

1988

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The ATP content of round spermatids isolated from hamsters was decreased 90% after 18 h of incubation in the presence of 4 microM-(-)gossypol and 0.10% bovine serum albumin (BSA). The (+)-enantiomer had no effect under these incubation conditions. The Michaelis-Menten constant Km and the maximal initial velocity Vmax of cellular LDH-C4 were not significantly altered after 18 h of incubation of the spermatids with (-)gossypol. Furthermore, there was no effect of (-)gossypol on the production of 14CO2 from L-[U-14C]lactate. It is concluded that (-)gossypol does not inhibit ATP production in spermatids by an effect on the sperm-specific LDH-C4 enzyme or on the mitochondrial oxidation of pyruvate. Rather, (-)gossypol may have an effect on the coupling between electron transport and ATP synthesis in the mitochondria. This action of (-)gossypol may not involve the H+-conducting activity of gossypol, but could be produced through binding of (-)gossypol to specific mitochondrial proteins.

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Effect of gossypol on spermatozoal lactate dehydrogenase-X (LDH-X) in male rats

1987

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Monkey lactate dehydrogenase-C4 as a model for the interaction of enzymes with gossypol

Cited by 9 publications

References 36 publications

Differential effects of (+)- and (-)-gossypol enantiomers on LDH-C4 activity of hamster spermatogenic epithelium in vitro

Differential effects of (+)- and (-)-gossypol enantiomers on LDH-C4 activity of hamster spermatogenic epithelium in vitro

Mechanism of action of (-)gossypol on ATP production in isolated hamster spermatids

Effect of gossypol on spermatozoal lactate dehydrogenase-X (LDH-X) in male rats

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