Food is.... Energy! Review concepts Catabolism: Metabolic reaction pathways that break down food molecules and release biochemical energy. Anabolism: Metabolic reactions that build larger biological molecules from smaller pieces. ** Refer to sections 21.1 and 21.2 1
Review concepts Many metabolic reactions are redox Reactions. Coenzymes continuously cycle between their oxidized and reduced forms. Ex: NAD + and NADH/H + NADP + and NADPH + /H + FAD/FADH 2 Review concepts Exergonic and Endergonic reactions: G = H T S Spontaneous reactions release free energy, which is available to do work. Exergonic reactions have A negative G value. Endergonic reactions are a nonspontaneous reaction or process that absorbs free energy and has a positive G. ** Refer to sections 21.1 and 21.2 2
What is Acetyl-S-CoA? An important metabolic intermediate for breakdown of all classes of food. It is a thiol and can react with acids to form a thioester. Aids in transfer of acetyl groups, (i.e acetyltransferase ) 23.2 Glucose Metabolism: An Overview When glucose enters a cell from the bloodstream, it is immediately converted to glucose 6-phosphate. Once this phosphate is formed, glucose is trapped within the cell because phosphorylated molecules cannot cross the cell membrane. Like the first step in many metabolic pathways, the formation of glucose-6-phosphate is highly exergonic and not reversible in the glycolytic pathway, thereby committing the initial substrate to subsequent reactions. 3
Glucose-6-phosphate can enter the pentose phosphate pathway. This multistep pathway yields two products of importance to our metabolism One is a supply of the coenzyme NADPH, a reducing agent that is essential for various biochemical reactions. The other is ribose 5-phosphate, which is necessary for the synthesis of nucleic acids (DNA and RNA). When energy is needed, glucose 6-phosphate undergoes glycolysis to pyruvate and then to acetyl-s-coa, which enters the citric acid cycle. 23.3 Glycolysis Step 1. Conversion of Glucose Glucose-6-phosphate Step 2. Glucose-6-phosphate Pyruvate (via several steps of Glycolysis pathway) Step 3. Pyruvate Acetyl-ScoA Following: Glucose to Acetyl-ScoA (formation of the 6-phos phate is highly exergonic, and irreversible) 4
23.3 Glycolysis Glycolysis is a series of 10 enzyme-catalyzed reactions that break down glucose molecules. The net result of glycolysis is the production of two pyruvate molecules, two ATPs, and two NADH/H + s. Glycolysis Steps 1-5 of glycolysis break one glucose molecule down into two D-glyceraldehyde 3-phosphate fragments. An investment of 2 ATP molecules is required. Steps 6-10 occur twice for each glucose that enters in at step 1. Steps 6-10 produce: 2 pyruvates, 4 ATPs, 2 NADH/H + per glucose molecule For complete reactions of glucose to pyruvate: Figure 23.3, page 720 of text 5
23.5 What happens to Pyruvate? A decarboxylation reaction NAD + reduces to NADH S-CoA is dehydrogenated Why do we call this an oxidation? Structure of the multienzyme complex Pyruvate Dehydrogenase, has a core of 24 proteins. What happens to Pyruvate? Anaerobic: In the absence of oxygen. If electron transport slows because of insufficient oxygen, NADH concentration increases, NAD + is in short supply, and glycolysis cannot continue. An alternative way to reoxidize NADH is essential because glycolysis, the only available source of fresh ATP, must continue. The reduction of pyruvate to lactate solves the problem. 6
21.7 What happens to Acetyl-SCoA? 21.7 Citric Acid Cycle (a.k.a TCA cycle, Krebs cycle) -Takes place in mitochondria. The acetyl group is converted To CO 2 (redox?) -Cyclic pathway, why? Explain the reaction from the Citric Acid cycle and the enzyme class that will act as catalysts. 7
Net result of the Citric Acid Cycle The net result of the citric acid cycle is: -Production of four reduced coenzyme molecules, 3 NADH and 1 FADH 2 -Conversion of an acetyl group to two CO 2 molecules -Production of one energy-rich molecule (GTP) The eight steps of the citric acid cycle are shown in greater detail on Section 21.8 of your text. 23.7 Regulation of Glucose Metabolism and Energy Production Normal blood glucose concentration a few hours after a meal ranges roughly from 65 to 110 mg/dl. Hypoglycemia: Lower-than normal blood glucose concentration. Hyperglycemia: Higher-than normal blood glucose concentration. 8
Two hormones from the pancreas have the major responsibility for blood glucose regulation. The first, insulin, is released when blood glucose concentration rises. The second hormone, glucagon, is released when blood glucose concentration drops. 23.8 Metabolism in Fasting and Starvation 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 15 20 hours of normal activity (3 hours in a marathon race). 9
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. 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. 10
23.9 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. 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 II diabetes is thought to result when cell membrane receptors fail to recognize insulin. Drugs that increase either insulin or insulin receptor levels are an effective treatment because more of the undamaged receptors are put to work. Type I diabetes is classified as an autoimmune disease, a condition in which the body misidentifies some part of itself as an invader. Gradually, the immune system wrongly identifies pancreatic beta cells as foreign matter, develops antibodies to them, and destroys them. To treat Type I diabetes, the missing insulin must be supplied by injection. 11
Blood glucose concentration in glucose tolerance test for normal and diabetic individuals. Metabolism of TriAcylGlycerols Pathways that break down molecules (catabolism) are shown in light brown, and synthetic pathways (anabolism) are shown in blue. Connections to other pathways or intermediates of metabolism are shown in green. 12
25.5 Oxidation of Fatty Acids Once a fatty acid enters the cytosol of a cell that needs energy, three successive processes must occur. 1. Activation: The fatty acid must be activated by conversion to fatty acyl-scoa. Some energy from ATP must initially be invested in converting the fatty acid to fatty acyl-scoa, a form that breaks down more easily. 2. Transport: The fatty acyl-scoa must be transported into the mitochondrial matrix where energy generation will occur. Carnitine, a transmembrane protein found only in the mitochondrial membrane, specifically moves fatty acyl-scoa across the membrane into the mitochondria. 3. Oxidation: The fatty acyl-scoa must be oxidized by enzymes in the mitochondrial matrix to produce acetyl-scoa plus the reduced coenzymes to be used in ATP generation. The oxidation occurs by repeating the series of four reactions which make up the β-oxidation pathway. 13
β-oxidation refers to the oxidation of the carbon atom β to the thioester linkage in two steps of the pathway. STEP 1: The first β oxidation: The oxidizing agent FAD removes hydrogen atoms from the carbon atoms α and β to the C=O group in the fatty acyl-scoa, forming a carbon carbon double bond. STEP 2: Hydration: A water molecule adds across the newly created double bond to give an alcohol with the OH group on the β-carbon. STEP 3: The second β oxidation: NAD + is the oxidizing agent for conversion of the β ΟΗ group to a carbonyl group. STEP 4: Cleavage to remove an acetyl group: An acetyl group is split off and attached to a new coenzyme A molecule, leaving behind an acyl-scoa that is two carbon atoms shorter. 14
The four steps of the β-oxidation pathway: 25.6 Energy from Fatty Acid Oxidation The total energy output from fatty acid catabolism is measured by the total number of ATPs produced. Current best estimates are that 2.5 ATPs result from each NADH and 1.5 ATPs from each FADH 2. The β-oxidation pathway produces 1 NADH and 1 FADH 2 or 4 ATPs per cycle. Each acetyl-scoa produces 3 NADH, 1 FADH 2 and 1 ATP or 10 ATPs per acetyl-scoa. Lauric acid, CH 3 (CH 2 ) 10 COOH, has 12 carbons. 15
After initial activation (-2 ATP), five β-oxidations (5x4 ATP = +20 ATP) will change lauric acid into 6 acetyl-scoa molecules (6x10 ATP = + 60 ATP). The total energy yield is 78 ATP per lauric acid. 1 mole (200g) lauric acid yields 78 moles ATP 1 mole (180g) glucose yields 30-32 moles ATP Fats and oils yield 9 Calories per gram Carbohydrates yield 4 Calories per gram Each gram of glycogen can hold as much as 2 grams of water so fats are almost 7 times more energy dense than carbohydrates in the body. Practice questions section C 6 H 12 O 6 + 6 O 2 6 CO 2 + 6 H 2 O G = 686 kcal/mol The oxidation of glucose, shown above, is an important reaction in the body. This reaction is 1. endergonic, as represented by energy diagram (a). 2. exergonic, as represented by energy diagram (a). 3. endergonic, as represented by energy diagram (b). 4. exergonic, as represented by energy diagram (b). 16
In the pathways for the digestion of food and the production of biochemical energy, the oxidation of Acetyl-SCoA occurs in 1. stage 1: digestion. 2. stage 2: Acetyl-SCoA production. 3. stage 3: citric acid cycle. 4. stage 4: ATP production. 21.5 Write the products of Hydrolysis: 17
What is the general class of enzyme that catalyzes this process? 21.24 In which step is a coenzyme needed? Identify the coenzyme. b) In which step is carbon dioxide evolved and a hydrogen ion added? c) Which of the structures shown can be described as a beta-keto acid? 18
Normal metabolism as well as unusual stresses can produce reactive oxygen species capable of injuring cells. In the induction stage of the Atkins diet ketosis is induced in which blood glucose levels drop and blood ketone bodies increase. Which of the compounds below are ketone bodies? OH O CH 3 CH CH 2 C O 3-Hydroxybutyrate O O CH 3 C CH 2 C O Acetoacetate 1. Acetone 2. Acetone and acetoacetate 3. 3-Hydroxybutyrate 4. All of the above O CH 3 C CH 3 Acetone 19
When blood glucose levels rise following a meal, which of the following events occurs first? 1. Blood levels pass through normal to below normal. 2. Glycolysis occurs to replenish the ATP supplies. 3. Glucose is absorbed by the cells. 4. Insulin levels rise. The conjugate base of the bile acid cholic acid and cholesterol are shown below. To what general class of compounds do they belong? 1. Eicosanoids 2. Fatty acids 3. Glycolipids 4. Steroids 20