Disease relevance of Skf 34288

• Effects in vivo of food deprivation and 3-mercaptopicolinate in the glycogen-storage-disease (gsd/gsd) rat [1].
• A similar pattern of hypoglycemia and possibly of associated counterregulatory responses elicited by treatment with the phosphoenolpyruvate carboxykinase inhibitor 3-mercaptopicolinic acid could account for only a 2-fold induction of Glc-6-Pase mRNA [2].
• Catheterized conscious fasted rats were injected intravenously (i.v.) with either saline, LPS (1 mg/100 g body weight [BW], lethal dose [LD] 100), or 3-mercaptopicolinic acid (3-MP), an inhibitor of gluconeogenesis [3].

High impact information on Skf 34288

• When PEPCK activity was inhibited in vivo with 3-mercaptopicolinic acid (MPA), thallus photosynthesis decreased by 70% and became sensitive to O2 [4].
• 3-Mercaptopicolinic acid inhibits gluconeogenesis and is a potent hypoglycemic agent in the fasting state [5].
• In all animals treated with 3-mercaptopicolinic acid, plasma lactate concentrations rose markedly, as did the rate of hepatic lipogenesis [6].
• The inhibition of chicken liver phosphoenolpyruvate carboxykinase by 3-mercaptopicolinic acid (3-MP) has been investigated [7].
• 3-Mercaptopicolinic acid, an inhibitor of phosphoenolpyruvate carboxykinase, was without effect on the parameters studied, suggesting that this enzyme is not involved in the decarboxylation reaction [8].

Chemical compound and disease context of Skf 34288

• Unfortunately, when Burt used 3-mercaptopicolinate to inhibit gluconeogenesis and thereby induce hypoglycemia in fasted tumor-bearing subjects, infused glycerol served as gluconeogenic substrate, raising the serum glucose level [9].

Biological context of Skf 34288

• 3-Mercaptopicolinate. A reversible active site inhibitor of avian liver phosphoenolpyruvate carboxykinase [7].
• 3-Mercaptopicolinate inhibited uptake and esterification of [1-14C]oleate, slightly increased 14CO2 production from [1-14C]oleate and greatly increased the [3-hydroxybutyrate]/[acetoacetate] ratio [10].
• Half-maximal inhibition was observed at 0.58 mM 3-mercaptopicolinate, which agrees with the IC50 value (0.47 mM) for the inhibition in vitro of phosphoenolpyruvate carboxykinase activity [11].
• 3-Mercaptopicolinic acid and energy metabolism in the liver fluke, Fasciola hepatica [12].

Anatomical context of Skf 34288

• Kinetic studies with purified P-enolpyruvate carboxykinase from rat liver cytosol indicate that 3-mercaptopicolinate is a noncompetitive inhibitor with respect to both oxalacetate and MnGTP2-, and that simulataeous saturation with both substrates does not diminish this inhibition [13].
• The actions of the hormones of 14CO2 production from [I-14C]oleate by hepatocytes from starved rats in the presence of 3-mercaptopicolinate thus have the characteristics of the response to the hormones found with hepatocytes from fed rats incubated without 3-mercaptopicolinate [10].
• The effect of 3-mercaptopicolinic acid and substrate interactions on the incorporation of lipogenic precursors into glyceride-glycerol, glyceride-fatty acids and nonesterified fatty acids in bovine adipose tissue [14].
• The effects of 3-mercaptopicolinic acid, an inhibitor of phosphoenolpyruvate carboxykinase, were studied in bovine subcutaneous adipose tissue slices in vitro [14].
• The inhibition of gluconeogenesis in isolated kidney tubules by 3-mercaptopicolinate, a specific inhibitor of the phosphoenolpyruvate carboxykinase reaction, is species specific [15].

Associations of Skf 34288 with other chemical compounds

• This inhibitory effect was reversed completely when 3-mercaptopicolinate was removed and the rate of glucose synthesis returned to normal values within 2 min [13].
• Both the ATP- and ADP-dependent decarboxylation of oxalacetate and the carboxylation activity of phosphoenolpyruvate carboxykinase are inhibited by 3-mercaptopicolinic acid while phosphoenolpyruvate carboxylase and ribulose-1,5-bisphosphate carboxylase are not inhibited [16].
• At 4 h after a single intraperitoneal injection of 3-mercaptopicolinate into NH4Cl-fed rats, NH3 excretion was inhibited by 93% [17].
• By using 3-mercaptopicolinate to determine the flux control coefficient of phosphoenolpyruvate carboxykinase we found that phenobarbital pretreatment led to an increase in this coefficient from 0.3 (controls) to 0.8 (phenobarbital group) [18].
• Effects of 3-mercaptopicolinic acid and a derivative of chlorogenic acid (S-3483) on hepatic and islet glucose-6-phosphatase activity [19].

Gene context of Skf 34288

• The hypoglycemic agent 3-mercaptopicolinic acid inhibits gluconeogenesis from lactate by isolated, perfused livers from fasted rats and guinea pigs [13].
• Furthermore, 3-mercaptopicolinate blocked the glucagon- and phenylephrine-stimulated 14CO2 production from [1-14C]lactate [20].

Analytical, diagnostic and therapeutic context of Skf 34288

• Animals were assigned to one of three major groups according to diet and/or drug treatment: (1) a mixed-diet control group; (2) a low-carbohydrate (LC)/high-fat-diet group; and (3) a low-carbohydrate-diet group treated with 3-mercaptopicolinic acid (MPA), an inhibitor of gluconeogenesis [21].
• Although the molecular mass does not appear to be altered, the pH sensitivity to 3-mercaptopicolinate inhibition and the enzyme recovery after immunoprecipitation both seemed to be affected [22].
• To this end, we studied the effects of a selective hepatic vagotomy on the hormonal response to a 30-min treadmill run (26 m/min, 0% grade) in adrenodemedullated rats injected with 3-mercaptopicolinic acid, a gluconeogenic inhibitor [23].
• When gluconeogenesis was blocked with 0.15 mM 3-mercaptopicolinate, an inhibitor of phosphoenolpyruvate carboxykinase, QO2 increased together with TNa as perfusion pressure was raised [24].

References