Gluconeogenesis result

A. Normal gluconeogenesis in the absence of ethanol consumption. B. Inhibition of gluconeogenesis resulting from hepatic metabolism of ethanol. 

Use of acetyl groups for gluconeogenesis results, in effect, in withdrawal of intermediates from the Krebs cycle. If continued, this withdrawal would result in cessation of the cycle. The total quantities of these intermediates present in the liver are relatively small, compared with the amount of protein in the body available for breakdown and conversion to glucose. Hence, it would make little sense to deplete the intermediates in the liver for use in gluconeogenesis. 

That the effect of corticosteroids on gluconeogenesis results from an indirect effect on protein metabolism is unlikely. Sometimes the effect of cortisone on protein and carbohydrate metabolism is not quantitatively related. When corticosteroid hormones are administered to fed animals, considerable changes in glycogen deposition are induced, but there are no changes in the rate of protein catabolism. 

The overall result of gluconeogenesis is summarized by the following equation ... 

In adipose tissue, the effect of the decrease in insulin and increase in glucagon results in inhibition of lipo-genesis, inactivation of lipoprotein lipase, and activation of hormone-sensitive lipase (Chapter 25). This leads to release of increased amounts of glycerol (a substrate for gluconeogenesis in the liver) and free fatty acids, which are used by skeletal muscle and liver as their preferred metabolic fuels, so sparing glucose. 

Triose phosphate isomerase (TPI) catalyzes the interconversion of glyceralde-hyde-3-phosphate and dihydoxyacetone phosphate and has an important role in glycolysis, gluconeogenesis, fatty acid synthesis, and the hexose monophosphate pathway. Red blood cell TPI activity measured in vitro is approximately 1000 times that of Hx, the least active glycolytic enzyme. TPI is a dimer of identical subunits, each of molecular weight 27,000, and does not utilize cofactors or metal ions. Posttranslational modification of one or both subunits may occur by deamidination, resulting in multiple forms of the enzymes and creating a complex multibanded pattern on electrophoresis. 

Cortisol-induced lipolysis not only provides substrates for gluconeogenesis (formation of glucose from noncarbohydrate sources) but it also increases the amount of free fatty acids in the blood. As a result, the fatty acids are used by muscle as a source of energy and glucose is spared for the brain to use to form energy. 

Adrenaline increases the rate of gluconeogenesis it binds to the a-receptor on the surface of the liver cell, which results in an increase in cytosolic concentration of Ca " ions (Chapter 12). This increases the activity of the Ca " -catmodulin-dependent protein kinase which phosphory-lates and causes similar changes in the activities of the enzymes PFK-2 and pyruvate kinase to those resulting from activation of cyclic-AMP-dependent protein kinase. Hence Ca " ions increase the rate of gluconeogenesis. 

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