Gluconeogenesis location

Name the major organs that carry out gluconeogenesis. Locate the various enzymes of gluconeogenesis in cell compartments. 

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. 

Figure 6.25 The intracellular location of the gluconeogenic enzymes. The gluconeogenic enzymes are located in the cytosol, except for pyruvate carboxylase which is always present within the mitochondria phosphoenolpyruvate carboxykinase is cytoplasmic in some species including humans. Consequently phosphoenolpyruvate must be transported across the inner mitochondrial enzyme by a transporter molecule in order for gluconeogenesis to take place.

In eukaryotes, the cytoplasm, representing slightly more than 50% of the cell volume, is the most important cellular compartment. It is the central reaction space of the cell. This is where many important pathways of the intermediary metabolism take place—e.g., glycolysis, the pentose phosphate pathway, the majority of gluconeogenesis, and fatty acid synthesis. Protein biosynthesis (translation see p. 250) also takes place in the cytoplasm. By contrast, fatty acid degradation, the tricarboxylic acid cycle, and oxidative phosphorylation are located in the mitochondria (see p. 210). 

TVace the pathway of each precursor through gluconeogenesis. Indicate the location of 14C in all intermediates and in the product, glucose. 

Oxaloacetate, formed in the mitochondria, must enter the cytosol where the other enzymes of gluconeogenesis are located. However,... 

The main site of gluconeogenesis is the liver, although it also occurs to a far lesser extent in the kidneys. Very little gluconeogenesis occurs in brain or muscle. Within liver cells, the first enzyme of gluconeogenesis, pyruvate carboxylase, is located in the mitochondrial matrix. The last enzyme, glucose 6-phosphatase is bound to the smooth endoplasmic reticulum. The other enzymes of the pathway are located in the cytosol. 

Pyruvate carboxylase is a mitochondrial matrix enzyme whereas the other enzymes of gluconeogenesis are located outside the mitochondrion. Thus oxaloacetate, produced by pyruvate carboxylase, needs to exit the mitochondrion. However the inner mitochondrial membrane is not permeable to this compound. Thus oxaloacetate is converted to malate inside the mitochondrion... 

Figure 16.24. Pathway of Gluconeogenesis. The distinctive reactions and enzymes of this pathway are shown in red. The other reactions are common to glycolysis. The enzymes for gluconeogenesis are located in the cytosol, except for pyruvate carboxylase (in the mitochondria) and glucose 6-phosphatase (membrane bound in the endoplasmic reticulum). The entry points for lactate, glycerol, and amino acids are shown.

A species specificity mi ht be pointed out with respect to the location of PE PC K, an enzyme used for gluconeogenesis, OAA is converted to PEP by PEPCK in the liver Cytoplasm of rats and mice because PEPCK is a cytosolic enzyme in these animals. In the livers of chickens and rabbits, however, OAA is converted to PEP in the mitochondria, because PEKK is mitochondrial in these animals, PEP must then be transported to the cytosol. PEPCK is evenly distributed between the mitochondria and the cytosol in human and cow livers (Pilkis et itf., 1988). 

The crystal structure of the entire 6-phosphofructo-2-kinase/fructose 2,6-bisphosphatase, a key bifunctional regulator of both glycolysis and gluconeogenesis, has been solved at 2.0 A resolution. The entire enzyme is a homodimer of 55kDa subunits arranged in a head-to-head fashion, with each monomer consisting of an independent kinase and phosphatase domain. The location of y-5 -ATP and inorganic phosphate in the kinase and phosphatase domains,... 

PCK1 Phosphoenolpyruvate carboxykinase, key enzyme in gluconeogenesis, catalyzes early reaction in carbohydrate biosynthesis, glucose represses transcription and accelerates mRNA degradation, regulated by Mcmlp and Cat8p, located in the cytosol... 

Comparison of the reactions of glycolysis and gluconeogenesis. All the reactions of glycolysis occur in the cytoplasm of the cell. However, in many human cells, pyruvate carboxylase is found in the mitochondria and phosphoenolpyruvate carboxykinase is located in the cytoplasm. Oxaloacetate, the product of the reaction catalyzed by pyruvate carboxylase, is shuttled out of the mitochondria and into the cytoplasm by a complex set of reactions. 

Unlike fats and carbohydrates, which are stored within the body, protein gains or losses can be more immediate indicators of nutritional changes affecting the animal. However, given that more than 50% of the body s albumin is located in extravascu-lar spaces and the half-life of albumin, plasma albumin may take some time to fall, while some other smaller proteins synthesized in the liver may fall more quickly because they have shorter half-lives. Increased gluconeogenesis may occur following dietary alterations and lead to changes of the plasma aminotransferases. 

Glucose 6-phosphatase is located in the membrane of the endoplasmic reticulum. It is used not only in gluconeogenesis, but also to produce blood glucose from the breakdown of liver glycogen. 

Chemistry, mechanism, and effects Glucagon is the product of the A cells of the endocrine pancreas. Like insulin, glucagon is a peptide but unlike insulin, glucagon acts on G protein-coupled receptors. Activation of glucagon receptors, which are located in heart, smooth muscle, and liver, stimulates adenylyl cyclase and increases intracellular cAMP. This results in increases in the heart rate and the force of contraction, increased hepatic glycogenolysis and gluconeogenesis and relaxation of smooth muscle. The smooth muscle effect is particularly marked in the gut. 

Oxaloacetate is formed from pyruvate by pyruvate carboxylase, located in the mitochondria. Pyruvate carboxylase is a biotin-requiring enzyme its kinetic mechanism has been studied in detail using the enzyme purified from domestic fowl liver (Attwood Graneri, 1992). In tissues where PEPCK is located in the cytosol, its substrate oxaloacetate is required in the cytosol for the formation of PEP for gluconeogenesis. The malate-aspartate shuttle is required for gluconeogenesis in avian kidney, according to the scheme in Fig. 3.3, but whether or not it is also required for gluconeogenesis in avian liver is unresolved. There is evidence for the existence of a... 

As is true in the opposing processes of glycolysis and gluconeogenesis, the pathways for the opposing processes of fatty acid degradation and fatty acid synthesis are not simply the reverse of each other. The processes are separate from each other, utilize different enzyme systems, and are even located in different cellular compartments. Degradation by the P-oxidation pathway takes place in cellular mitochondria, whereas biosynthesis of fatty acids occurs in the cytoplasm. 

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