1 CHAPTER 22 Metabolic Pathways for Carbohydrates What is this chapter about? 2 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. A. Metabolism and Cell Structure 3 Catabolic reactions: breaking down complex molecules Anabolic reactions: building up larger molecules from simple ones Releases energy Requires energy And remember that we have two cell types: Prokaryotic: simple Eukaryotic: more complex Cell Structure for Metabolism 4 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. B. ATP and Energy 5 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. ATP is Coupled with Reactions 6 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! Example: Coupling ATP Hydrolysis with a Reaction 7 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 C. Important Coenzymes in Metabolic Pathways 8 Reminder: What is oxidation? What is reduction? NAD+ (nicotinamide adenine dinucleotide) 9 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 FAD (flavin adenine dinucleotide) 10 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 carboncarbon double bond Coenzyme A (CoA) 11 Made of several components… Main function: activation of acyl groups, producing a thioester D. Digestion of Carbohydrates 12 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. E. Glycolysis: Oxidation of Glucose 13 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. What happens in glycolysis? 14 1. 2. 3. 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) Regulation of Glycolysis? 15 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. F. Pathways for Pyruvate 16 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 So, let’s think. 17 When you’re working out really hard, why might lactate accumulate in the muscles? Fermentation 18 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. G. Glycogen Metabolism 19 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. Glycogenesis (glycogen synthesis) 20 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. Glycogenolysis 21 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 Regulation of Glucose Metabolism 22 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. H. Gluconeogenesis: Glucose Synthesis 23 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. The Cori Cycle 24 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. Regulation of Gluconeogenesis 25 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.