Inhibition of succinate dehydrogenase and beta-hydroxybutyrate dehydrogenase activities by methylmalonate in brain and liver of developing rats.
The effects of methylmalonate (MMA) on succinate dehydrogenase (SDH) and beta-hydroxybutyrate dehydrogenase (HBDH) activities in brain and liver of 15-day-old rats were studied. The apparent Km of SDH for succinate was 0.45 mmol/L in brain and 0.34 mmol/L in liver. MMA inhibited the enzyme activity in both tissues with Ki values of 4.5 mmol/L and 2.3 mmol/L in brain and liver, respectively, and the inhibition was of the reversible competitive type. The calculated Km for HBDH with beta-hydroxybutyrate as substrate was 1.26 mmol/L in brain and 0.36 mmol/L in liver. MMA inhibited the enzyme with a Ki value of 0.015 mmol/L in brain and 0.275 mmol/L in liver. These results are probably relevant to our understanding of cerebral metabolism in methylmalonic acidaemic children, especially during ketoacidotic and hypoglycaemic crises, and may be related to the pathogenesis of cerebral dysfunction of methylmalonic acidaemia.
Dutra
J C
JC
Departamento de Bioquímica, Universidade Federal do Rio Grande do Sul, Alegre-RS, Brazil.
Dutra-Filho
C S
CS
Cardozo
S E
SE
Wannmacher
C M
CM
Sarkis
J J
JJ
Wajner
M
M
D000818:Animals; D000833:Animals, Suckling; D001921:Brain / Q000187:drug effects* / Q000201:enzymology / Q000254:growth & development; D006884:Hydroxybutyrate Dehydrogenase / Q000037:antagonists & inhibitors*; D008099:Liver / Q000187:drug effects* / Q000201:enzymology / Q000254:growth & development; D008764:Methylmalonic Acid / Q000493:pharmacokinetics / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013385:Succinate Dehydrogenase / Q000037:antagonists & inhibitors*
D008764:Methylmalonic Acid; D006884:Hydroxybutyrate Dehydrogenase; D013385:Succinate Dehydrogenase