PEPCK (phosphoenolpyruvate carboxykinase) has a key role in highly gluconeogenic tissues such as liver and kidney, converting lactateand other precursors to glucose and releasing the sugar into the bloodstream. SKF-34288 HCl is a PEPCK inhibitor which is a potent hypoglycemic agent via inhibition of glucose synthesis through the specific inhibition of PEPCK in the gluconeogenesis pathway[1]. Supplying MPA decreased xylem recycling in the leaf as there was an increase in the amount of amino acids, 2cm from the base and at the tip. Feeding MPA increased the volume of the xylem exudate and guttation fluid in the control leaves, except at the base. Feeding MPA clearly inhibited Asn metabolism and resulted in an increase in amino acids and amides in the xylem[2].
作用机制
Binding of SKF-34288 to the allosteric pocket stabilizes an altered conformation of the nucleotide-binding site that in turn reduces the affinity of the enzyme for the nucleotide[1].
SKF-34288 HCl 细胞实验
Cell Line
Concentration
Treated Time
Description
References
Rat kidney-cortex slices
0.1 and 0.01 mM
2 hours
Significant inhibition of glucose production (P<0.001)
Biochem J. 1974 Mar;138(3):387-94
Rice leaves
350 µM
24 hours
Inhibition of PEPCK activity, resulting in an increase in amino acids in the guttation fluid and xylem sap towards the leaf tip
J Exp Bot. 2016 Apr;67(9):2901-11
SKF-34288 HCl 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
Castor bean seedlings
Endosperm of castor bean seedlings
Topical application
2.5 mM
150 minutes
Inhibits phosphoenolpyruvate carboxykinase, restricting the production of phosphoenolpyruvate from oxaloacetate, thereby reducing gluconeogenesis. The amount of Fru-2,6-P2 in the treated endosperm increased to about 250% of the control level.
Plant Physiol. 1985 Feb;77(2):358-64
Udotea flabellum
Marine macroalga
Incubation in artificial seawater
3 mM
60 minutes
Inhibition of PEPCK activity, leading to a 70% decrease in photosynthesis and increased sensitivity to O2
Proc Natl Acad Sci U S A. 1991 Apr 1;88(7):2883-7
Rice (Oryza sativa L. Indica cultivar IR72)
Seedlings
Root feeding
350 µM
24 hours
Inhibition of PEPCK activity, resulting in an increase in amino acids in the xylem sap and guttation fluid towards the leaf tip
J Exp Bot. 2016 Apr;67(9):2901-11
Rats
Starved and alloxan-diabetic rats
Oral
37.5, 75, 150 mg/kg
Single dose, observed for 4 hours
Significant hypoglycemic effect in starved and diabetic rats, accompanied by increased blood lactate
Biochem J. 1974 Mar;138(3):387-94
Diatoms
Cells adapted to low pCO2
Direct addition to cell suspension
5 μM
Dark preincubation for 5 min
3-MPA is a classic inhibitor of phospho enolpyruvate carboxykinase, reducing photosynthetic O2 evolution by 90% in T. pseudonana. In T. weissflogii and P. tricornutum, 5 μM 3-MPA totally inhibited net CO2 fixation and O2 evolution.
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