PEP 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. 

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

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). 

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

Note that the C02 added to pyruvate in the pyruvate carboxylase step is the same molecule that is lost in the PEP carboxykinase reaction (Fig. 14-17). This carboxylation-decarboxylation sequence represents a way of activating pyruvate, in that the decarboxylation of oxaloacetate facilitates PEP formation. In Chapter 21 we shall see how a similar carboxylation-decarboxylation sequence is used to activate acetyl-CoA for fatty acid biosynthesis (see Fig. 21-1). 

When intermediates are shunted from the citric acid cycle to other pathways, they are replenished by several anaplerotic reactions, which produce four-carbon intermediates by carboxylation of three-carbon compounds these reactions are catalyzed by pyruvate carboxylase, PEP carboxykinase, PEP carboxylase, and malic enzyme. Enzymes that catalyze carboxylations commonly employ biotin to activate C02 and... 

As noted in the discussion of anaplerotic reactions (Table 16-2), phosphoenolpyruvate can be synthesized from oxaloacetate in the reversible reaction catalyzed by PEP carboxykinase ... 

T Glycogen phosphorylase I Glycogen synthase I PFK-1 T FBPase-2 i Pyruvate kinase T PEP carboxykinase T Triacylglycerol lipase Perilipin phosphorylation T Acetyl-CoA carboxylase... 

The first "roadblock" to overcome in the synthesis of glucose from pyruvate is the irreversible conversion in glycolysis of pyruvate to phosphoenolpyruvate (PEP) by pyruvate kinase. In gluconeogenesis, pyruvate is first carboxylated by pyruvate carboxylase to oxaloacetate (OAA), which is then converted to PEP by the action of PEP-carboxykinase (Figure 10.3). 

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

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