Zhang T M, Sener A, Malaisse W J
Laboratory of Experimental Medicine, Erasmus Medical School, Brussels Free University, Brussels, Belgium.
Arch Biochem Biophys. 1994 Oct;314(1):186-92. doi: 10.1006/abbi.1994.1428.
The metabolic fate and metabolic effects of succinic acid methyl esters were examined in rat isolated hepatocytes. Both the monomethyl ester (SAM) and dimethyl ester (SAD) of succinic acid inhibited D-glucose metabolism. Such an inhibition affected, in order of increasing severity, the direct incorporation of D-glucose into glycogen and futile cycling between the hexose and its 6-phosphate ester, the phosphorylation of D-glucose, the generation of triose phosphates from the hexose, and the production of 14C-labeled lactate, pyruvate, and amino acids from D-[U-14C]glucose and its oxidation. The dimethyl ester of [1,4-14C]succinic acid ([1,4-14C]SAD) or [2,3-14C]-succinic acid ([2,3-14C]SAD) was efficiently converted to acidic metabolites. The oxidation of [1,4-14C]SAD largely exceeded that of [2,3-14C]SAD. Inversely the generation of newly formed radioactive D-glucose and glycogen appeared higher in cells exposed to [2,3-14C]SAD, rather than [1,4-14C]SAD. It is proposed that SAM and SAD are suitable nutrients both to cover the energy need of hepatocytes and to act as gluconeogenic precursors.
在大鼠离体肝细胞中研究了琥珀酸甲酯的代谢命运和代谢效应。琥珀酸的单甲酯（SAM）和二甲酯（SAD）均抑制D-葡萄糖代谢。这种抑制作用按严重程度递增的顺序影响D-葡萄糖直接掺入糖原以及己糖与其6-磷酸酯之间的无效循环、D-葡萄糖的磷酸化、己糖生成磷酸丙糖，以及由D-[U-¹⁴C]葡萄糖生成¹⁴C标记的乳酸、丙酮酸和氨基酸及其氧化。[1,4-¹⁴C]琥珀酸二甲酯（[1,4-¹⁴C]SAD）或[2,3-¹⁴C]琥珀酸（[2,3-¹⁴C]SAD）能有效转化为酸性代谢产物。[1,4-¹⁴C]SAD的氧化在很大程度上超过[2,3-¹⁴C]SAD。相反，在暴露于[2,3-¹⁴C]SAD而非[1,4-¹⁴C]SAD的细胞中，新形成的放射性D-葡萄糖和糖原的生成似乎更高。有人提出，SAM和SAD都是合适的营养物质，既能满足肝细胞的能量需求，又能作为糖异生的前体。
