Dutra J C, Dutra-Filho C S, Cardozo S E, Wannmacher C M, Sarkis J J, Wajner M
Departamento de Bioquímica, Universidade Federal do Rio Grande do Sul, Alegre-RS, Brazil.
J Inherit Metab Dis. 1993;16(1):147-53. doi: 10.1007/BF00711328.
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.
研究了丙二酸单酰（MMA）对15日龄大鼠脑和肝脏中琥珀酸脱氢酶（SDH）及β-羟丁酸脱氢酶（HBDH）活性的影响。SDH对琥珀酸的表观米氏常数（Km）在脑中为0.45 mmol/L，在肝脏中为0.34 mmol/L。MMA抑制这两种组织中的酶活性，在脑和肝脏中的抑制常数（Ki）值分别为4.5 mmol/L和2.3 mmol/L，且抑制作用为可逆竞争性类型。以β-羟丁酸为底物时，HBDH的计算Km在脑中为1.26 mmol/L，在肝脏中为0.36 mmol/L。MMA抑制该酶，在脑中的Ki值为0.015 mmol/L，在肝脏中为0.275 mmol/L。这些结果可能有助于我们理解甲基丙二酸血症患儿的脑代谢，尤其是在酮症酸中毒和低血糖危象期间，并且可能与甲基丙二酸血症脑功能障碍的发病机制有关。
