Endoplasmic reticulum gluconeogenesis

This Mg2+-activated enzyme is found on the lumenal side of the endoplasmic reticulum of hepatocytes and renal cells (see Fig. 15-6). Muscle and brain tissue do not contain this enzyme and so cannot carry out gluconeogenesis. Glucose produced by gluconeogenesis in the liver or kidney or ingested in the diet is delivered to brain and muscle through the bloodstream. 

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. 

ATP plays a central role in cellular maintenance both as a chemical for biosynthesis of macromolecules and as the major soirrce of energy for all cellular metabolism. ATP is utilized in numerous biochemical reactions including the eitric acid cycle, fatty acid oxidation, gluconeogenesis, glycolysis, and pyruvate dehydrogenase. ATP also drives ion transporters sueh as Ca -ATPase in the endoplasmic reticulum and plasma membranes, H+-ATPase in the lysosomal membrane, and Na+/K+-ATPase in the plasma membrane. Chemieal energy (30.5 kJ/mol) is released by the hydrolysis of ATP to adenosine diphosphate (ADP). 

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.

In eucaryotic cells, glycolysis, gluconeogenesis and fatty acid synthesis takes place in the cytosol, while the Krebs cycle is isolated within mitochondria glycogen is made in glycogen granules, lipid is synthesized in the endoplasmic reticulum and lysosomes carry on a variety of hydrolytic activities. As in procaryotic cells, ribosomes in the cytosol are the site of protein synthesis. 

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. 

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