Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:1.3.5.1 (succinate dehydrogenase)
 8,177 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The excretion, distribution and metabolism of DBP were studied in rats. More than 90% of the dose was excreted in the urine within 48 h following intravenous or oral administration, but the faecal excretion was low. Biliary excretion was remarkably higher than that in the faeces when DBP was given orally. No significant retention was observed in organs and tissues at 24 h after dosing. In vitro experiments showed that DBP was hydrolysed very rapidly to MBP by the esterase of rat liver microsome. DBP was found to be a strong inhibitor for the succinate dehydrogenase of rat liver. DBP and its metabolites, MBP and phthalic acid, did not produce any striking effect upon hepatic and serum enzyme activities in vitro. Urinary metabolites of orally ingested DBP were investigated in 3 species, namely, rats, hamsters and guinea pigs. MBP was a common major metabolite in all 3 species. A further increment was apparently excreted as the glucuronide in the rat, hamster and guinea pig together with a small amount of phthalic acid and unchanged DBP. Omega- or omega-1 oxidation products of MBP were also detected in the urine.
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PMID:Biochemical studies on phthalic esters. III. Metabolism of dibutyl phthalate (DBP) in animals. 65 32

Isolated rat liver mitochondria were exposed to mono- and di-n-butyl phthalate (MBP and DBP) and mono- and di(2-ethylhexyl)phthalate (MEHP and DEHP) and examined for effects on mitochondrial energy-dependent processes, including oxidative phosphorylation and active K+ uptake. Additional studies on the effects of these phthalate esters on succinate oxidation and on mitochondrial membrane integrity are also included. DBP and MEHP stimulated succinate state 4 respiration, impaired K+-valinomycin induced swelling with succinate, ascorbate, or ATP as the energy sources, and inhibited succinate state 3 respiration and succinate cytochrome c reductase activity. MEHP was found to act as a non-competitive inhibitor of succinate dehydrogenase activity, with an apparent Ki = 2.4 X 10(-4) M. At concentrations which uncouple energy linked reactions, MEHP and DBP produced only slight energy-independent swelling and release of soluble proteins from isolated mitochondria. MBP caused only slight stimulation of state 4 respiration and impairment of K+-valinomycin induced swelling with each of the 3 energy sources, however, of the 4 phthalate esters, it produced the greatest energy-independent swelling and led to the greatest release of soluble mitochondrial proteins. DEHP had no apparent effect on any of these processes except for slight impairment of ATP-dependent K+-valinomycin induced swelling. It is concluded that phthalate ester toxicity in liver mitochondria is due to uncoupling of energy linked reactions and/or inhibition of succinate dehydrogenase activity. Uncoupling by MBP may involve disruption of mitochondrial membrane integrity, while uncoupling by DBP and MEHP is probably due to an increase in membrane permeability to H+ and other small ions.
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PMID:Effect of phthalate esters on energy coupling and succinate oxidation in rat liver mitochondria. 396 78