Glucose metabolism in the liver

Liver normally is a glucose producing rather than glucose using tissue. However after a meal containing carbohydrate it becomes a glucose consumer. Approx 60% of glucose is absorbed by the liver from the portal vein. This increased glucose metabolism is caused by a number of metabolic changes:

1- Increased transport of glucose into the liver. Glucose is transported by GLUT-2 transporters into the liver (insulin insensitive). These transporters have a high Km for glucose which allows them to be responsive to a high glucose concentration after a meal without becoming saturated. GLUT-2 transporters can also transport glucose from hepatocytes when blood glucose is low.

2- Phosphorylation of glucose. Glucose is rapidly phosphorylated to glucose-6-P upon entering the liver. This effectively traps them inside the cells. Glucose-6-P is polar and cannot leave the liver cells. The liver expressed 2 sugar kinases, hexokinase and glucokinase which perform this action. Hexokinase is active in most cells, and will phosphorylate glucose as well as other sugars. Hexokinase has a low Km and a high affinity for glucose. Glucokinase is active in liver and islet cells of the pancreas and is specific for glucose. Glucokinase has a high Km and low affinity for glucose. In skeletal muscle cells hexokinase is under allosteric control by glucose-6-P in that high levels of G-6-P inhibit hexokinase. In the liver Insulin positively regulates glucokinase activity.

3- Increased glycogen synthesis. Glycogen synthesis is stimulated by high insulin levels, activating glycogen synthase. Glycose-6-P also allosterically activates glycogen synthase

4- Increased glycolysis and conversion to pyruvate. Glycolysis results in glucose converted to pyruvate. Levels of F-2,6-diP increase, favoring glycolysis over gluconeogenesis. Pyruvate kinase activated. Pyruvate further metabolized through TCA to meet energy needs of liver.

5- Increased activity of the PPP. This pathway produced NADPH in particular which along with excess acetyl CoA from glycolysis is used in fatty acid synthesis.

6- Excess CHO is converted into lipid. Lipid synthesis and CHO metabolism are linked via acetyl CoA. Excess CHO that cannot be stored as glycogen, used in glycolysis or the TCA cycle is shunted into lipogenesis. The liver is the primary tissue for de novo lipid synthesis.

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