PEPCK carboxykinase

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. 

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. 

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+. 

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

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). 

FIGURE 11.2 Interactions of vanadium with the hormone-sensitive G protein modulated cAMP producing signal transduction system. Bold lines with arrows leading away from V represent stimulation, blunt-ended lines represent inhibition. V shows where vanadium interactions have geen found. Pase phosphatase, PDE(IV) phosphodiesterase (IV), PEPCK phosphoenolpyrurate carboxykinase, PKA, protein kinse A inactive, PKAa PKA active. This figure was adapted from [13]. 

Most cestodes which have been investigated, however, conform to the second category, type 2, which is characterised by a C02-fixation step. Carbohydrate is degraded to the level of PEP by glycolysis, the steps involved being similar to those in mammalian tissue. At this point, the enzymes pyruvate kinase and phosphoenolpyruvate carboxykinase (PEPCK) compete for available substrate and a branch-point occurs (Fig. 5.4). The relative activities of these two enzymes determine the fate of the PEP and the subsequent types and amounts of end-products formed (see below). 

Hadziosmanovic, A. Kravica, S. (1982). [The activity of phosphoenolpyruvate carboxykinase (PEPCK.) and pyruvate kinase (PK) in some parasitic helminths.] In Russian. Veterinarski Arkiv, 52 55-63. [HA/52/1493]... 

Figure 18.8 Gluconeogenesis pathway in the liver. PC is pyruvate carboxylase PEPCK is phosphoenolpyruvate carboxykinase. (Reproduced by permission from ViduesJ, Sovik O. Gluconeogenesis in infancy and childood. Acta Paediatr Scand 65 307-312, 1976.)...

Figure 10-4. Postnatal changes in newborn rat liver cytosolic phosphoenolopyruvate carboxykinase (PEPCK) activity and gluconeogenic rate in vivo from [14C-lactate]. Reprinted with permission from Girard et al. (1992).

The glucocorticoid cortisol is secreted from the adrenal cortex as a stress response under the control of adrenocorticotropic hormone (ACTH, corticotropin) produced by the anterior pituitary. Cortisol promotes catabolism by inducing synthesis of specific proteins. Cortisol binds to a cytosolic cortisol receptor which then translocates to the nucleus and switches on the expression of specific genes, notably that for PEP carboxykinase (PEPCK). Cortisol-induced expression of the key gluconeogenesis enzyme PEPCK increases levels of the enzyme and hence increases gluconeogenesis and available blood glucose. The cAMP-and cortisol-mediated pathways for induction of PEPCK expression are further linked by CREB-dependent expression of a coactivator protein PGC-1 that promotes cortisol-dependent expression of PEPCK. 

---