Glycogen Metabolism 23.8 Gluconeogenesis: Glucose Synthesis Chapter 23 Metabolic Pathways for Carbohydrates

2 Glycogenesis Glycogenesis: Stores glucose by converting glucose to glycogen. Operates when high levels of glucose-6- phosphate are formed in the first reaction of glycolysis. Does not operate when energy stores (glycogen) are full, which means that additional glucose is converted to body fat.

3 Diagram of Glycogenesis

4 Formation of Glucose-6-Phosphate Glucose is converted to glucose-6-phosphate using ATP. Glucose-6-phosphate

5 Formation of Glucose-1-Phosphate Glucose-6-phosphate is converted to glucose-1-phosphate. Glucose-6-phosphate Glucose-1-phosphate

6 UDP-Glucose UTP activates glucose-1-phosphate to form UDP-glucose and pyrophosphate (PP i ). UDP-glucose

7 Glycogenesis: Glycogen The glucose in UDP-glucose adds to glycogen. UDP-Glucose + glycogen glycogen-glucose + UDP The UDP reacts with ATP to regenerate UTP. UDP + ATP UTP + ADP

8 Glycogenolysis is the break down of glycogen to glucose.

9 Glycogenolysis Glycogenolysis: Is activated by glucagon (low blood glucose). Bonds glucose to phosphate to form glucose-1- phosphate. Glycogen-glucose + P i Glycogen + glucose-1-phosphate

10 Isomerization of Glucose-1- phosphate The glucose-1-phosphate isomerizes to glucose- 6-phosphate, which enters glycolysis for energy production.

11 Glucose-6-phosphate Glucose-6-phosphate: Is not utilized by brain and skeletal muscle because they lack glucose-6-phosphatase. Hydrolyzes to glucose in the liver and kidney, where glucose-6-phosphatase is available providing free glucose for the brain and skeletal muscle.

12 Utilization of Glucose Glucose: Is the primary energy source for the brain, skeletal muscle, and red blood cells. Deficiency can impair the brain and nervous system.

13 Gluconeogenesis: Glucose Synthesis Gluconeogenesis is: The synthesis of glucose from carbon atoms of noncarbohydrate compounds. Required when glycogen stores are depleted.

14 Gluconeogenesis: Glucose Synthesis Carbon atoms for gluconeogenesis from lactate, some amino acids, and glycerol are converted to pyruvate or other intermediates. Seven reactions are the reverse of glycolysis and use the same enzymes. Three reactions are not reversible. Reaction 1Hexokinase Reaction 3Phosphofructokinase Reaction 10Pyruvate kinase

15 Gluconeogenesis: Pyruvate to Phosphoenolpyruvate Pyruvate adds a carbon to form oxaloacetate by two reactions that replace the reverse of reaction 10 of glycolysis. Then a carbon is removed and a phosphate added to form phosphoenolpyruvate.

16 Phosphoenolpyruvate to Fructose- 1,6-bisphosphate Phosphoenolpyruvate is converted to fructose- 1,6-bisphosphate using the same enzymes in glycolysis.

17 Glucose Formation A loss of a phosphate from fructose-1,6- bisphosphate forms fructose-6-phosphate and P i. A reversible reaction converts fructose-6- phosphate to glucose-6-phosphate. The removal of phosphate from glucose-6- phosphate forms glucose.

18 Cori Cycle When anaerobic conditions occur in active muscle, glycolysis produces lactate. The lactate moves through the blood stream to the liver, where it is oxidized back to pyruvate. Gluconeogenesis converts pyruvate to glucose, which is carried back to the muscles. The Cori cycle is the flow of lactate and glucose between the muscles and the liver.

19 Pathways for Glucose

20 Regulation of Glycolysis and Gluconeogenesis High glucose levels and insulin promote glycolysis. Low glucose levels and glucagon promote gluconeogenesis.

21 Ethanol Ethanol is not a carbohydrate, nor is it a precursor for the biosynthesis of carbohydrates. However, ethanol can replace sizable amounts of carbohydrates as an energy source when large amounts are ingested. It is present in the blood of most humans, being produced by intestinal flora. People ingest ethanol in variable amounts in beverages and fermented fruits. Ethanol is metabolized in the liver to acetate and adds to the caloric content of the diet. Ethanol has an energy equivalent of 7 kcal/g. 100 mL of table wine has ethanol corresponding to about 72 kcal. A “jigger” of whiskey furnishes approximately 120 kcal.

22 Ethanol continue: When ethanol is metabolized in the liver, alcohol dehydrogenase oxidizes it first to acetaldehyde. CH 3 CH 2 OH + NAD + → CH 3 CHO + NADH + H + The acetaldehyde is oxidized further to acetate. CH 3 CHO + NAD + + H 2 O → CH 3 COO - + NADH + H + A small fraction of the alcohol may be oxidized by other systems: Cytochrome P 450 oxidase (also involved in detoxification of many drugs); Catalase The acetate produced from ethanol largely escapes from the liver and is converted to acetyl CoA and then to carbon dioxide by the way of the Krebs cycle. The acetyl that stays in the liver may act as a precursor for lipid biosynthesis. A significant consequence of metabolism of ethanol in the liver is the twofold to threefold increase in the NADH/NAD + ratio. With higher concentrations of blood alcohol, the concentration of NADH remains high, and the availability of NAD + drops and limits both the further oxidation of ethanol and the normal functioning of other metabolic pathways, such as gluconeogenesis.

23 “Fatty liver” Chronic consumption of significant amounts of alcohol may lead to a “fatty liver”, in which the excess of triacylglyceride is deposited. This is caused by several contributing factors: Reduced triacylglyceride secretion from the liver Reduced rates of fatty acid oxidation Increased rates of lipid biosynthesis These processes are associated with the increased acetyl CoA and NADH/NAD + ratio in the liver that results from ethanol oxidation.