4.! What happens to pyruvate once it is formed? Be able to describe the pathways involving pyruvate and their respective outcomes.!

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1 1.! What happens during digestion of carbohydrates? Be able to describe carbohydrate digestion, its location, the enzymes involved, and name the major products of this process.! 2.! What are the major pathways in the metabolism of glucose? Be able to identify the pathways by which glucose is (1) synthesized and (2) broken down, and describe their interrelationships.! 3.! What is glycolysis? Be able to give an overview of the glycolysis pathway and its products, and to identify where the major monosaccharides enter the pathway. 4.! What happens to pyruvate once it is formed? Be able to describe the pathways involving pyruvate and their respective outcomes.! 5.! How is glucose metabolism regulated, and what are the influences of starvation and diabetes mellitus? Be able to identify the hormones that influence glucose metabolism and describe the changes in metabolism during starvation and diabetes mellitus.! 6.! What are glycogenesis and glycogenolysis? Be able to define these pathways and their purpose.! 7.! What is the role of gluconeogenesis in metabolism? Be able to identify the functions, substrates, and products of this pathway. 1 March 11, 2011

2 Digestion: Digestion entails the physical grinding, softening, and mixing of food, as well as the enzyme-catalyzed hydrolysis of carbohydrates, proteins, and fats.! -amylase: Digestion begins in the mouth,! -amylase in saliva catalyzes hydrolysis of the glycosidic bonds in carbohydrates. Salivary! -amylase continues to act on polysaccharides in the stomach until, after an hour or so, it is inactivated by stomach acid. No further carbohydrate digestion takes place in the stomach. Enzymes from the mucous lining of the small intestine hydrolyze maltose, sucrose and lactose to glucose, fructose, and galactose, which are then transported across the intestinal wall into the bloodstream. 2 March 11, 2011

3 Pentose phosphate pathway: 1. 3 March 11, 2011

4 2. Glucose-6-phosphate enters the pentose phosphate pathway when a cellʼs need for NADPH or ribose-5-phosphate exceeds its need for ATP. Glycogenesis Pathway: Glycolysis Pathway: 4 March 11, 2011

5 Glucose 6-phosphate can be converted to pentose products, stored as glycogen, or broken down to acetyl- SCoA for production of energy, proteins, or fats. 5 March 11, 2011

6 Glycolysis: 6 March 11, 2011

7 7 March 11, 2011

8 8 March 11, 2011

9 The major monosaccharides from digestion other than glucose also eventually join the glycolysis pathway. Fructose, from fruits or hydrolysis of the disaccharide sucrose, is converted to glycolysis intermediates in two ways: In muscle, it is phosphorylated to fructose 6-phosphate. In the liver, it is converted to glyceraldehyde 3-phosphate. Mannose is a product of the hydrolysis of plant polysaccharides other than starch. Mannose is converted by hexokinase to a 6-phosphate, which then undergoes a multistep, enzyme-catalyzed rearrangement and enters glycolysis as fructose 6-phosphate. 9 March 11, 2011

10 Galactose from hydrolysis of the disaccharide lactose is converted to glucose 6- phosphate by a five-step pathway. A hereditary defect affecting any enzyme in this pathway can be a cause of galactosemia. Aerobic: 10 March 11, 2011

11 Anaerobic: 11 March 11, 2011

12 NADH serves as the reducing agent and is reoxidized to NAD + which is then available in the cytosol for glycolysis. Lactate formation serves no purpose other than NAD + production, and the lactate is reoxidized to pyruvate when oxygen is available. Fermentation: Alcoholic Fermentation: 12 March 11, 2011

13 The total energy output from oxidation of glucose is the combined result of (a) (b) (c) (d) The total number of ATPs per glucose molecule is the 4 ATPs from glucose catabolism plus the number of ATPs produced for each reduced coenzyme that enters electron transport. 13 March 11, 2011

14 For a long time, based on the belief that 3 ATPs are generated per NADH and 2 ATPs per FADH2 the maximum yield was taken as 38 ATPs. 10 NADH(3ATP/NADH) + 2 FADH2 (2ATP/FADH2 ) + 4 ATP = 38 ATP The 38 ATPs per glucose molecule is viewed as a maximum yield of ATP, most likely possible in bacteria and other prokaryotes. In humans and other mammals, the maximum is most likely ATPs per glucose molecule. Normal blood glucose concentration a few hours after a meal ranges roughly from 65 to 110 mg/ dl. Hypoglycemia: Hyperglycemia: 14 March 11, 2011

15 Low blood glucose (hypoglycemia) causes weakness, sweating, and rapid heartbeat, and in severe cases, low glucose in brain cells causes mental confusion, convulsions, coma, and eventually death. The brain can use only glucose as a source of energy. At a blood glucose level of 30 mg/ dl, consciousness is impaired or lost, and prolonged hypoglycemia can cause permanent dementia. High blood glucose (hyperglycemia) causes increased urine flow as the normal osmolarity balance of fluids within the kidney is disturbed. Prolonged hyperglycemia can cause low blood pressure, coma, and death. Two hormones from the pancreas have the major responsibility for blood glucose regulation. Insulin: Glucagon: 15 March 11, 2011

16 The metabolic changes in the absence of food begin with a gradual decline in blood glucose concentration accompanied by an increased release of glucose from glycogen. All cells contain glycogen, but most is stored in liver cells (about 90 g in a 70 kg man) and muscle cells (about 350 g in a 70 kg man). Free glucose and glycogen represent less than 1% of our energy reserves and are used up in hours of normal activity (3 hours in a marathon race). During the first few days of starvation, protein is used up at a rate as high as 75 g /day. Lipid catabolism is mobilized, and acetyl- SCoA molecules derived from breakdown of lipids accumulate. Acetyl- SCoA begins to be removed by a new series of metabolic reactions that transform it into ketone bodies. 16 March 11, 2011

17 As starvation continues, the brain and other tissues are able to switch over to producing up to 50% of their ATP from catabolizing ketone bodies instead of glucose. By the 40th day of starvation, metabolism has stabilized at the use of about 25 g of protein and 180 g of fat each day. So long as adequate water is available, an average person can survive in this state for several months; those with more fat can survive longer. 17 March 11, 2011

18 Diabetes mellitus: The symptoms by which diabetes is usually detected are excessive thirst accompanied by frequent urination, abnormally high glucose concentrations in urine and blood, and wasting of the body despite a good diet. These symptoms result when available glucose does not enter cells where it is needed. Type I: Type II: 18 March 11, 2011

19 Diabetic individuals are subject to several serious conditions that result from elevated blood glucose levels. Excess glucose is reduced to sorbitol. Sorbitol is not transported out of the cell. Its rising concentration increases the osmolarity of fluid in the eye, causing increased pressure, cataracts, and blindness. Elevated sorbitol is also associated with blood vessel lesions and gangrene in the legs. Ketoacidosis: Hypoglycemia: Glycogenesis: 19 March 11, 2011

20 Glycogenolysis: 20 March 11, 2011

21 Gluconeogenesis: Steps 1, 3, and 10 in glycolysis are too exergonic to be directly reversed. Gluconeogenesis uses reactions catalyzed by different enzymes that reverse these steps. The 7 other steps of glycolysis are reversible because they operate at near-equilibrium conditions. 21 March 11, 2011

22 Gluconeogenesis begins with conversion of pyruvate to phosphoenolpyruvate, the reverse of the highly exergonic step 10 of glycolysis. Two steps are required, utilizing two enzymes and the energy provided by two triphosphates, ATP and GTP. 22 March 11, 2011

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