Carboxykinase

It is worth noting that the reaction catalyzed by PEP carboxykinase (Eigure 20.25) could also function as an anaplerotic reaction, were it not for the particular properties of the enzyme. COg binds weakly to PEP carboxykinase, whereas oxaloacetate binds very tightly K, = 2 X 10 Af), and, as a result, the enzyme favors formation of PEP from oxaloacetate. 

COMPARTMENTALIZED PYRUVATE CARBOXYLASE DEPENDS ON METABOLITE CONVERSION AND TRANSPORT The second interesting feature of pyruvate carboxylase is that it is found only in the matrix of the mitochondria. By contrast, the next enzyme in the gluconeogenic pathway, PEP carboxykinase, may be localized in the cytosol or in the mitochondria or both. For example, rabbit liver PEP carboxykinase is predominantly mitochondrial, whereas the rat liver enzyme is strictly cytosolic. In human liver, PEP carboxykinase is found both in the cytosol and in the mitochondria. Pyruvate is transported into the mitochondrial matrix, where it can be converted to acetyl-CoA (for use in the TCA cycle) and then to citrate (for fatty acid synthesis see Figure 25.1). /Uternatively, it may be converted directly to 0/ A by pyruvate carboxylase and used in glu-... 

FIGURE 23.6 The PEP carboxykinase reaction. GTP formed in this reaction can be converted to ATP by nucleoside diphosphate kinase, althongh liver cells in some species may not contain this enzyme. 

Hanson, R. W., and Reshef, L., 1997. Regulation of phosphoenolpyruvate carboxykinase (GTP) gene expression. Annual Review of Biochemistry 66 581-611. 

Step 2 of Figure 29.13 Decarboxylation and Phosphorylation Decarboxylation of oxaloacetate, a jB-keto acid, occurs by the typical retro-aldol mechanism like that in step 3 in the citric acid cycle (Figure 29.12), and phosphorylation of the resultant pyruvate enolate ion by GTP occurs concurrently to give phosphoenol-pyruvate. The reaction is catalyzed by phosphoenolpyruvate carboxykinase. 

Gluconeogenesis 1 TORC2, others l Expression PEP carboxykinase, glucose-6-phosphatase Liver... 

Gene activated Lipoprotein lipase fatty acid transporter protein adipocyte fatty acid binding protein acyl-CoA synthetase malic enzyme GLUT-4 glucose transporter phosphoenolpyruvate carboxykinase... 

In pigeon, chicken, and rabbit liver, phospho-enolpymvate carboxykinase is a mitochondrial enzyme, and phosphoenolpyruvate is transported into the cytosol for gluconeogenesis. In the rat and the mouse, the enzyme is cytosolic. Oxaloacetate does not cross the mitochondrial inner membrane it is converted to malate, which is transported into the cytosol, and convetted back to oxaloacetate by cytosolic malate dehydrogenase. In humans, the guinea pig, and the cow, the enzyme is equally disttibuted between mitochondria and cytosol. 

Phosphoenolpyruvate carboxykinase i t Glucocorticoids, glucagon, epinephrine (cAMP) Insulin Glucagon ... 

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... 

Key PEP-CK = PEP carboxykinase this enzyme begins the re-cycling of carbon atoms derived from amino acids (via pyruvate, 2-OG or OAA) or lactate (via pyruvate) to glucose (gluconeogenesis). 

Fmctose-6-phosphate to phosphofructokinase (PFK) Phosphoenolpyruvate carboxykinase (PEP CK) [ bypass route] Fructose-1,6 bisphosphatase... 

Following the conversion of pyruvate into oxaloacetate, phosphoenolpyruvate carboxykinase (PEP CK) catalyses a decarboxylation to form PEP (Figure 6.42). This... 

Figure 6.46 Pyruvate carboxylase (PC) and phosphoenotpyruvate carboxykinase (PEP CK) bypass reactions...

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. 

Answer A. Cortisol stimulates transcription of the PEP carboxykinase gene in the liver but not in adipose tissue. 

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