Ch. 23: Carbohydrate Metabolism

1. Ch. 23: Carbohydrate Metabolism

2. Introduction • Carbohydrate metabolism is mainly about how glucose is • converted to acetyl-SCoA for entrance into the citric acid cycle • stored and then released • synthesized when carbohydrates are in short supply Because of its importance, the body has several ways to maintain the glucose concentration in blood and providing it to cells that depend on it.

3. Digestion of Carbohydrates • We already learned that the first stage in catabolism is digestion. • digestion: a general term for the breakdown of food into small molecules • Digestion begins in the mouth, continues in the stomach, and ends in the small intestine. • Digestion involves: • physical grinding • softening • mixing of food • enzyme-catalyzed hydrolysis of carbohydrates, proteins, and fats. • The products of digestion are mostly small molecules that are absorbed from the intestine tract by villi.

4. Fig 23.1 The digestion of carbohydrates

5. Glucose Metabolism: An Overview • Glucose is the major source of energy in our body. • Glucose is converted into acetyl-S-coenzyme A at the initial stage of glucose metabolism. Acetyl-sCoA is the common intermediate in the catabolism of all foods. • The acetyl-sCoA proceeds down the central pathway of metabolism and the ultimate formation of ATP. • Glycolysis is the major pathway on the road to ATP synthesis. • Glycolysis: the biochemical pathway that breaks down a molecule of glucose into two molecules of pyruvate plus energy.

6. Glucose Metabolism Cont. • Glyconeogenesis is the reverse of glycolysis. • glyconeogenesis: the biochemical pathway for the synthesis of glucose from noncarbohydrates, such as lactate, amino acids, or glycerol

7. Fig 23.2 Glucose metabolism

8. Glucose Metabolism Cont. • When glucose enters a cell from the bloodstream, it is immediately converted to glucose 6-phosphate. (see p.664) • Once the phosphate is formed, glucose is trapped within the cell because the phosphate can not cross the cell membrane. • The formation of glucose 6-phosphate is highly exergonic and not reversible, so there must be additional reactions. • There are several paths the glucose 6-phosphate can take.

9. Pathways for Glucose 6-Phosphate • when energy is needed • glucose 6-phosphate undergoes glycolysis to pyruvate and then to acetyl-S-coenzyme A which enters the citric acid cycle. (the central, yellow, pathway) • when cells are already well supplied with glucose • the excess glucose is converted to other forms for storage: to glycogen by the glycogenesis pathway, or to fatty acids by lipid metabolism pathway. • when the cell’s need for NADPH or ribose-6-phosphate exceeds its need for ATP • the glucose-6-phosphate enters the pentose phosphate pathway

10. Pentose Phosphate Pathway • The biochemical pathway that produces ribose (a pentose), NADPH, and other sugar phosphates from glucose • This pathway produces two important products: • NADPH, a reducing agent that is essentially for various biochemical reactions. • 5-Phosphate of the sugar ribose, necessary for the synthesis of DNA and RNA.

11. Glycolysis • breaks down each glucose molecule into 2 pyruvate molecules plus energy (yields 2 ATPs and 2 NADHs in a series of 10 enzyme-catalyzed reactions). • Also called the Embden-Meyerhoff Pathway

12. Glycolyis • see p. 720, Figure 23.3 as we walk through the steps • Steps 1-3: phosphorylation • Glucose is carried in blood to cells and is transported across the cell membrane. • As soon as it enters the cell, the glucose is phosphorylated (step 1), which requires energy from ATP • Phosphates cannot cross the cell membrane, so the sugar phosphates are trapped in the cell. • The glucose 6-phosphate is isomerized to fructose 6- phosphate. • Fructose 6-phosphate reacts with ATP to add another phosphate group (becomes fructose 1,6-bisphosphate)

13. Glycolysis Cont. • steps 4-5: cleavage & isomerization • the bisphosphate is broken into 2 three-carbon monophosphates (one is a ketose phosphate, the other an aldose phosphate) • the two monophosphates are isomers and can interconvert • steps 1-5 require energy investment. • 2 ATP molecules have been invested

14. Glycolysis Cont. • steps 6-10: energy generation • oxidation of glyceradehyde by NAD+ • transfer of a phosphate from the bisphosphoglycerate to ADP to make ATP • isomerization and dehydration • transfer of a phosphate group to ADP Net result of glycolyis is: conversion of glucose to two pyruvates production of 2 ATP molecules production of 2 molecules of reduced coenzyme NADH

15. Entry of Other Sugars into Glycolysis • Major monosaccharides from digestion other than glucose can also enters into glycolysis pathway. • 1) Fructose from fruits or hydrolysis of the disaccharides sucrose is converted to glycolysis intermediates in two pathways: • In muscle, it is phosphorylated to fructose 6- phosphate. • In the liver, it is converted to glyceraldehyde 3- phosphate.

16. Entry of Other Sugars into Glycolysis Cont. • 2) Galactose (from hydrolysis of the disaccharide lactose) is converted to glucose 6-phosphate by a five-step pathway. • 3) Mannose, a product of hydrolysis of plant polysaccharides other than starch, is converted by hexokinase to a 6-phosphate which is then undergoes a multistep, enzyme catalyzed rearrangement and enters glycolysis as fructose 6-phosphate.

17. The Fate of Pyruvate • The conversion of glucose to pyruvate is a central metabolic pathway in most living organisms. • The further reactions of pyruvate depend on metabolic conditions and on the nature of organism. • Under normal oxygen rich (aerobic) conditions, pyruvate is converted to acetyl-S-coenzyme A.

18. Fate of Pyruvate Cont. • Under anaerobic (not enough oxygen) conditions, pyruvate is reduced to lactate. When sufficient oxygen becomes available, lactate is recycled to pyruvate. • When body is starved for glucose, pyruvate is converted back to glucose by gluconeogenesis. • Yeast is an organism that converts pyruvate to ethanol under anaerobic conditions.

19. Alcoholic Fermentation • fermentation: the production of energy under anaerobic conditions • alcoholic fermentation: the anaerobic breakdown of glucose to ethanol and CO2 by the action of yeast enzymes • used to produce beer, wine, other alcoholic beverages, bread

20. Energy Output in Complete Catabolism of Glucose • For every one glucose molecule, there is a maximum of 38 ATPs produced. In humans, the maximum is most likely 30-32 ATP’s per glucose molecule.

21. Regulation of Glucose Metabolism & Energy Production • Normal blood glucose concentration a few hours after a meal ranges roughly between 65 and 110 mg/dL. Departure from normal has serious effects on our body. • Low blood glucose (Hypoglycemia) causes weakness, sweating, and rapid heartbeat, and in severe cases it can cause coma, and eventually to death. • High blood glucose (Hyperglycemia) causes increased urine flow. Prolonged hyperglycemia can cause low blood pressure, coma, and death.

22. Blood glucose

23. The following two hormones from pancreas have the major responsibility for blood glucose regulation. • Insulin is released when blood glucose level rises. • Its role is to decrease blood glucose concentration by accelerating the passage of glucose into cells where it is used for energy production, and stimulating synthesis of glycogen, proteins, and lipids. • Glucagon is released when blood glucose concentration drops. • Glucagon stimulates the break down of glycogen in the liver and release glucose. Amino acids from proteins and glycerol from lipids are also converted to glucose in the liver by gluconeogenesis.

24. Metabolism in Fasting and Starvation • In the absence of food, blood glucose concentration gradually decreases at the same time release of glucose from glycogen increases. • As glucose and glycogen are exhausted, proteins break down into amino acids and glucose production from amino acids via gluconeogenesis in the liver takes place. • Acetyl-sCoA build up inside cells as a result of breakdown of lipids and is removed by a new series of metabolic reactions that transforms Acetyl-sCoA into ketone bodies.

25. Fig 23.7 Relative changes during early stages of starvation. • Ketone bodies: A group of compounds such as 3-hydroxybutarate, acetoacetate, and acetone, known as the ketone bodies.

26. The ketone bodies enters into the blood stream and as the starvation continues, the brain and other tissues start using ketone bodies to produce up to 50% of their ATP from catabolizing ketone bodies instead of glucose. • So long as adequate water is available, an average person can survive in this state for several months. People with more fat can survive longer.

27. Metabolism in Diabetes Mellitus • diabetes mellitus: a chronic condition due to either insufficient insulin or failure of insulin to activate crossing of cell membranes by glucose • Diabetes mellitus classified into two major classes: • Insulin dependent (type I diabetes or juvenile-onset diabetes) because it is often appears in childhood. It is caused by failure of the pancreatic cells to produce enough insulin. • Insulin independent or type II diabetes (also known as adult-onset diabetes) since it is often appears in obese adults of over 40 years of age.

28. Diabetes Cont. • Cause of this type II diabetes is not due to the lack of insulin but due to the failure to promote passage of glucose across the cell membranes. • In addition to glucose metabolism, diabetes affects protein and fat metabolism. • Glucose does not enters into cells where it is needed rather builds up in blood causing the symptoms of hyperglycemia and spilling over into the urine. • Metabolic response to the shortage of glucose within cells causes breakdown of proteins and fats.

29. Conditions that Result From Elevated Blood Sugar Levels • Blindness due to cataracts • Ketoacidosis (results from buildup of acidic ketones in the late stages of uncontrolled diabetes) can lead to coma and diminished brain function. • Hypoglycemia or insulin shock due to overdose of insulin or failure to eat can cause nerve damage or death.

30. Glycogen Metabolism: Glycogenesis and Glycogenolysis • glycogenesis: the biochemical pathway for synthesis of glycogen • occurs when glucose concentrations are high. • begins with glucose 6-phosphate and occurs via three steps shown on the bottom right in Fig 23.8. • glycogenolysis: the biochemical pathway for breakdown of glycogen to free glucose. • occurs in two steps as shown on the bottom left in Fig 23.8.

31. In muscle cells glycogenolysis occurs when there is an immediate need for energy. In the liver, glycogenolysis occurs when blood glucose is low. • Fig 23.8 Glycogenolysis and glycogenesis.

32. Gluconeogenesis: Glucose from Noncarbohydrates • Gluconeogenesis occurs mainly in the liver. • It is the pathway for making glucose from noncarbohydrate molecules such as lactate, amino acids, and glycerol. • This pathway becomes critical during fasting and the early stages of starvation.

33. 2. The glucose returns via the bloodstream to the muscles to be stored as glycogen or used for energy production. • Fig 23.9 Glucose production during exercise. • The “Cori Cycle” 1. Lactate produced in muscles under anaerobic conditions during exercise is sent to the liver where it is converted back to glucose.

34. Chapter Summary • Monosaccharide products of carbohydrate digestion such as glucose, fructose, and galactose enter the blood stream from the small intestine. • Glycolysis is the major pathway for glucose metabolism and pyruvate is the end product of glycolysis. • One alternative pathway for glucose metabolism is glycogenesis, the synthesis of glycogen. • Another alternative pathway for glucose metabolism is the pentose phosphate pathway, which provides five-carbon sugars and NADPH.

35. Chapter Summary Contd. • When oxygen is in good supply, pyruvate is transported into mitochondria and converted to acetyl-SCoA for energy via the citric acid cycle and oxidative phosphorylation. Where there is insufficient oxygen, pyruvate is reduced to L-lactate with the production of NAD+. • Insulin is produced when blood glucose concentration rises, accelerates glycolysis ands glycogen synthesis.

36. Chapter Summary Contd. • Glucagon is produced when blood glucose concentration drops, accelerate production of glucose in the liver from stored glycogen and from other other precursors via gluconeogenesis pathway. • Diabetes mellitus may be insulin dependent (pancreas fails to produce insulin) or non-insulin dependent (insulin receptor fails to recognize insulin). • Among the serious outcomes of uncontrolled diabetes are cataract, blood vessel lesions, ketoacidosis, and hypoglycemia.