CHAPTER 22

1. CHAPTER 22 Metabolic Pathways for Carbohydrates

2. What is this chapter about? • When you eat food, what happens to it? • The sum total of chemical reactions in the body to break down or build molecules = metabolism • Metabolic pathway = reactions linked together in a series • This chapter introduces metabolism, then focuses on carbohydrates. Other macromolecules will come in future chapters.

3. A. Metabolism and Cell Structure • Catabolic reactions: breaking down complex molecules • Releases energy • Anabolic reactions: building up larger molecules from simple ones • Requires energy • And remember that we have two cell types: • Prokaryotic: simple • Eukaryotic: more complex

4. Cell Structure for Metabolism • Eukaryotic cells are more complex, having • Nucleus • Organelles in the cytoplasm, such as • Ribosomes • Mitochondria • Lysosomes • Rough and smooth endoplasmic reticulum • Golgi complex • Prokaryotes don’t have any of those – not even a nucleus.

5. B. ATP and Energy • Energy obtained from the food we eat is used to form ATP (adenosine triphosphate) • Hydrolysis of ATP = energy ATP + H2O  ADP + Pi + 7.3 kcal/mole • When we take in food, the reverse reaction occurs.

6. ATP is Coupled with Reactions • There are certain reactions in our body that need to happen, but require energy. • Example: first step to break down glucose in the cell is to add a phosphate group. But this requires 3.3 kcal/mol. • How do these reactions happen??? • Couple the endothermic reaction with the hydrolysis of ATP -- this will drive the reaction requiring energy. • Example on next page!

7. Example: Coupling ATP Hydrolysis with a Reaction Glucose + Pi + 3.3 kcal/mol --> glucose-6-phosphate ATP --> ADP + Pi + 7.3 kcal/mol ------------------------------------------------------------- Glucose + ATP --> ADP + glucose-6-phosphate + 4.0 kcal/mol

8. C. Important Coenzymes in Metabolic Pathways • Reminder: What is oxidation? • What is reduction?

9. NAD+ (nicotinamide adenine dinucleotide) • Formed from a derivative of the vitamin niacin bonded to an ADP • NAD+ gets reduced to NADH, generally participating in reactions producing a carbon-oxygen double bond

10. FAD (flavin adenine dinucleotide) • Derived from riboflavin plus an ADP • FAD gets reduced to FADH2 (2 nitrogens in the flavin accept hydrogens) • Typically participates in reactions that produce a carbon-carbon double bond

11. Coenzyme A (CoA) • Made of several components… • Main function: activation of acyl groups, producing a thioester

12. D. Digestion of Carbohydrates • Digestion: conversion of larger molecules into smaller ones that the body can absorb • First step: chewing the food in the mouth. Enzyme in saliva -- salivary amylase -- breaks the larger polysaccharides into smaller units. • Disaccharides are broken into monosaccharides in the small intestine. • Still in the small intestine, these monosaccharides are absorbed through the intestinal wall into the bloodstream. The liver converts fructose and galactose to glucose.

13. E. Glycolysis: Oxidation of Glucose • There are 10 steps in glycolysis. You do not need to memorize them for this class! Hooray! • But I will give you a general overview (there are three main phases). • No oxygen is required for glycolysis (anaerobic). • For one glucose molecule through glycolysis, net result 2 ATP and 2 NADH.

14. What happens in glycolysis? • 2 ATP are invested • Glucose (a 6 carbon sugar) is split into 2 3 carbon pieces (glucose is lysed… hence the name glycolysis!) • Energy payout -- 2 NADH and 4 ATP (which gives you the net result of 2)

15. Regulation of Glycolysis? • When there are large amounts of glucose-6-phosphate (product of step 1) present, hexokinase (enzyme for 1st step) is inhibited. • High cellular AMP/ADP levels indicate that much of the cellular ATP has been used up. • Conversely, when cellular ATP is plentiful, several of the glycolytic enzymes (phosphofructokinase, pyruvate kinase) are inhibited by ATP -- the cell does not need to make any more ATP. • When ATP levels drop, the enzymes are activated once again.

16. F. Pathways for Pyruvate • Pyruvate = end product of glycolysis • What happens to pyruvate after glycolysis? • Depends on if there’s oxygen present. • Aerobic conditions (oxygen): pyruvate oxidized (requiring NAD+), CO2 removed, the remaining acetyl group attached to coenzyme A -- called acetyl CoA • Anaerobic conditions (no oxygen): pyruvate reduced to lactate (in muscle tissue), or reduced to ethanol via the fermentation process (in microorganisms) • Both of the anaerobic pathways recycle NADH back to NAD+ • Both of the anaerobic pathways produce a very small amount of ATP

17. So, let’s think. When you’re working out really hard, why might lactate accumulate in the muscles?

18. Fermentation • Conversion of pyruvate first to acetaldehyde, then to ethanol • A CO2 is first removed from pyruvate (decarboxylation) then acetaldehyde is reduced to ethanol with the help of NADH • This CO2 is the bubbles produced in beer and champagne. Thus, this process is performed primarily by yeast.

19. G. Glycogen Metabolism • Glycogen: long-term storage of glucose. Stored in skeletal muscles and liver. • When the amount of glucose we consume exceeds our immediate needs, the excess can be synthesized into glycogen for later use. • This is used when we have insufficient blood glucose • When our glycogen stores are full, any remaining blood glucose is converted to triglycerides and stored as body fat.

20. Glycogenesis (glycogen synthesis) • Glycogen contains glucose units linked by  1,4 and 1,6 glycosidic bonds. • When we eat polysaccharides, they are digested and provide us with individual glucose units to synthesize glycogen. • Regarding the reactions themselves, know that the process requires ATP. 

21. Glycogenolysis • The breakdown of glycogen -- provides us with glucose when blood glucose is depleted • Many organs (red blood cells, brain, skeletal muscles) require glucose to function properly

22. Regulation of Glucose Metabolism • When blood glucose levels are low, the hormone glucagon is released. This hormone accelerates the rate of glycogenolysis and inhibits the synthesis of glycogen. • When blood glucose levels are high (after a meal), the hormone insulin is released. This hormone accelerates glycogen synthesis and glycogen degradation through processes such as glycolysis. Insulin also inhibits glucose synthesis.

23. H. Gluconeogenesis: Glucose Synthesis • Not all of our glucose comes from glycogen stores -- some of it comes from carbon/hydrogen/oxygen atoms available to the cell. • Gluconeogenesis reactions are, for the most part, the reverse of glycolysis (except for three out of the 10 steps). • By not making it the exact reverse, we bypass three reactions that require energy, making gluconeogenesis energetically favorable.

24. The Cori Cycle • Glucose can also be made from lactate, a byproduct of vigorous exercise. • Lactate builds up in the muscles and is transported to the liver, where gluconeogenesis occurs. • Meanwhile, glucose (being formed in the liver) is transported to the muscle to rebuild glycogen stores. • The flow of lactate and glucose between the muscles and liver is known as the Cori cycle.

25. Regulation of Gluconeogenesis • If you eat a high carbohydrate diet, not much gluconeogenesis occurring. • When you are eating a low carbohydrate diet, the gluconeogenesis pathway is very active. • At any point, if the cell is in need of glucose, glycolysis is turned off.