PEPCK

Phosphoenolpyruvate carboxykinase (PEPCK) deficiency is distinctly rare and even more devastating clinically than deficiencies of glucose-6-phosphatase or fructose-1,6-bisphosphatase. PEPCK activity is almost equally distributed between a cytosolic form and a mitochondrial form. These two forms have similar molecular weights but differ by their kinetic and immunochemical properties. The cytosolic activity is responsive to fasting and various hormonal stimuli. Hypoglycemia is severe and intractable in the absence of PEPCK [12]. A young child with cytosolic PEPCK deficiency had severe cerebral atrophy, optic atrophy and fatty infiltration of liver and kidney. 

PEPCK phosphoenolpyruvate carboxykinase RGS regulators of G protein signaling... 

The oxidative decarboxylation reaction above is part of the TCA cycle and leads to the formation of oxaloacetate, which maybe used to synthesize citrate (with acetyl-CoA) or may be used as a substrate by phosphoenol pyruvate carboxykinase, PEPCK. It should be noted that the phosphoenolpyruvate generated by PEPCK reaction shown above is... 

Phosphoenolpyruvate carboxykinase (PEPCK) catalyzes a critical reaction in gluconeogenesis, which under many conditions is the rate-limiting step in the pathway. A cAlVfP response element (CRE) and a glucocorticoid response element (GRE) are each located upstream from the transcription start site. 

Cortisol induces PEPCK gene expression by the following sequence ... 

Binds (through the zinc fingers) to the glucocorticoid response element (GRE) associ-. ated with the PEPCK gene, which... 

These effects of CREB and the cortisol-receptor complex are not entirely independent of each other. Each contributes, along with several other transcription factors, to assembling a complex of activator proteins that ultimately determine the level of PEPCK gene expression. 

Phosphorylation of gene regulatory proteins such as CREB to control gene expression, usually over several hours. The typical result is to add more enzyme to the cell. CREB induces the phosphoenolpyruvate carboxykinase (PEPCK) gene. 

Phosphoenolpyruvate carboxykinase (PEPCK) in the cytoplasm is induced by glucagon and cortisol. It converts OAA to phosphoenolpyruvate (PEP) in a reaction that requires GTP. PEP continues in the pathway to fructose 1,6-bisphosphate. 

I Hepatic phosphoenol-pyruvate carboy- (iii) kinase (PEPCK) activity... 

Oxaloacetate is decarboxylated and phosphorylated in the cytosol by PEP-carboxykinase (also referred to as PEPCK) The reaction is... 

In animals and in many bacteria, PEP is formed by decarboxylation of oxaloacetate. In this reaction, which is catalyzed by PEP carboxykinase (PEPCK), a molecule of GTP, ATP, or inosine triphosphate captures and phosphorylates the enolate anion generated by the decarboxylation (Eq. 13-46).252 The stereochemistry is such that C02 departs from the si face of the forming enol.253 The phospho group is transferred from GTP with inversion at the phosphorus atom 254 The enzyme requires a divalent metal ion, preferably Mn2+. 

In some organisms, such as the parasitic Ascaris suum, PEPCK functions principally as a means of synthesis of oxaloacetate by reaction of PEP with C02... 

Oxaloacetate is also decarboxylated without phosphorylation of the enolate anion formed but with release of free pyruvate. Both pyruvate kinase and PEPCK can act as oxaloacetate decarboxylases.261... 

Phosphoenolpyruvate (PEP) 510, 510s, 685s key metabolic intermediate 705, 706 as stabilized enol 697 Phosphoenolpyruvate carboxykinase 549 Phosphoenolpyruvate carboxykinase (PEPCK) 706... 

Gao, K, GifFin, B F, Morris, R E, Cardell, E L, and Cardell, R. R (1994) Optimal visualization of immunogold-silver staining of hepatic PEPCK with epipolarized light microscopy J Histochem Cytochem 42, 823-826. 

In this malate dismutation pathway, carbohydrates are degraded to phosphoenolpyruvate (PEP) via the classical glycolytic pathway. This PEP is then carboxylated by PEP carboxykinase (PEPCK) to oxaloacetate, which is subsequently reduced to malate. This malate is transported into the mitochondria and is degraded in a split pathway. A portion of the malate is oxidized to acetate and another portion is reduced to succinate, which can then be further metabolized to propionate (Fig. 20.1). 

One should bear in mind, however, that the fate of PEP at the PK/PEPCK branch point cannot simply be estimated by measuring the ratio of PK and PEPCK activities in vitro, as the use of PEP in each reaction is determined by Km values and substrate concentrations, by the extent of phosphorylation of PK, by the presence of (in)activators and by the rate of the subsequent reactions. 

Mouse (C57BL/6N) once (GO) Hepatic 1 M 3 M (increased relative liver weight and EROD activity decreased PEPCK activity) Weber et al. 1995... 

---