title: Metabolic effects and fate of succinic acid methyl esters in rat hepatocytes.
abstract: 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.
authors.affiliation: Laboratory of Experimental Medicine, Erasmus Medical School, Brussels Free University, Brussels, Belgium.
authors.forename: T M
authors.initials: TM
authors.lastname: Zhang
authors.forename: A
authors.initials: A
authors.lastname: Sener
authors.forename: W J
authors.initials: WJ
authors.lastname: Malaisse
mesh_terms: D000596:Amino Acids / Q000378:metabolism; D000818:Animals; D004952:Esters / Q000378:metabolism; D005260:Female; D005943:Gluconeogenesis; D005947:Glucose / Q000378:metabolism; D006003:Glycogen / Q000378:metabolism; D007773:Lactates / Q000378:metabolism; D019344:Lactic Acid; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D010084:Oxidation-Reduction; D010766:Phosphorylation; D011773:Pyruvates / Q000378:metabolism; D019289:Pyruvic Acid; D051381:Rats; D013386:Succinates / Q000378:metabolism / Q000494:pharmacology*
chemical_list: D000596:Amino Acids; D004952:Esters; D007773:Lactates; D011773:Pyruvates; D013386:Succinates; D019344:Lactic Acid; D019289:Pyruvic Acid; D006003:Glycogen; C056451:dimethyl succinate; D005947:Glucose; C041105:monomethyl succinate