PC30103 Biochemistry of Sports Lecture 3 - Carbohydrate Metabolism II PDF

PC30103: Biochemistry of Sports Lecture 3: Carbohydrate Metabolism II 24-10-2024  Revision: Sources of ATPs in your body Muscle cells (myocytes) have several different ways to make ATPs. These systems work together in 4 orders. Limited ATP storage...

PC30103: Biochemistry of Sports Lecture 3: Carbohydrate Metabolism II 24-10-2024  Revision: Sources of ATPs in your body Muscle cells (myocytes) have several different ways to make ATPs. These systems work together in 4 orders. Limited ATP storage 3S Phosphocreatine (PCr) 8-10S Anaerobic respiration (glycolysis, lactic acid metabolism and glycogenolysis) 90S Aerobic respiration (TCA cycle and electron transport chain, ETC) Very long!  Glycolysis (10 reactions) 1 2 How many ATPs are being Split one 6C *phosphofructokinase 3 produced via molecule to two 4 3C molecules! glycolysis? Reaction ATP Used 1, 3 -2 Produce (7, 10) X +4 from 2 6 molecules 5 7 Net +2 *2 molecules 10 9 8 Source: MacLaren, D., & Morton, J. (2012). Biochemistry for sport and exercise metabolism. UK: John Wiley & Sons.  The fate of pyruvate Pyruvate - end product of glycolysis. Once it has been formed, it passes into the mitochondria and is converted to acetyl-CoA in the so-called ‘link’ reaction. Key regulatory enzyme is known as pyruvate dehydrogenase (PDH). The formation of acetyl-CoA provides the crossroads between carbohydrate and fat oxidation, and so the control of PDH is seen as an important factor in the regulation of fat and carbohydrate metabolism.  The fate of pyruvate – “link” reaction Enter TCA cycle! Source: MacLaren, D., & Morton, J. (2012). Biochemistry for sport and exercise metabolism. UK: John Wiley & Sons. Inside a myocyte (muscle cell): cytoplasm versus mitochondria – aqueous environment Glycolysis (anaerobic) takes place in the cytoplasm. Pyruvate acetyl-CoA “link” reaction, mitochondrion. Within the mitochondrion, the TCA cycle (aerobic) occurs in the mitochondrial matrix. ETC or oxidative phosphorylation (aerobic) occurs at the internal folded mitochondrial membranes (cristae). (Source: https://www.yourgenome.org/facts/what-is-a-cell; https://en.wikipedia.org/wiki/Myocyte#/media/File:Blausen_0801_SkeletalMuscle.png; https://en.wikipedia.org/wiki/Inner_mitochondrial_membrane) Inside a myocyte (muscle cell): cytoplasm versus mitochondria – aqueous environment Glycolysis (anaerobic) takes place in the cytoplasm. Pyruvate acetyl-CoA “link” reaction, mitochondrion. Within the mitochondrion, the TCA cycle (aerobic) occurs in the mitochondrial matrix. ETC or oxidative phosphorylation (aerobic) occurs at the internal folded mitochondrial membranes (cristae). Why? (Source: https://www.yourgenome.org/facts/what-is-a-cell; https://en.wikipedia.org/wiki/Myocyte#/media/File:Blausen_0801_SkeletalMuscle.png; https://en.wikipedia.org/wiki/Inner_mitochondrial_membrane)  Today – aerobic respiration to produce more ATPs - TCA (citric acid cycle), ETC (oxidative phosphorylation) Sources: Demetrius, L., Magistretti, P., & Pellerin, L. (2014). Alzheimer's disease: The amyloid hypothesis and the Inverse Warburg effect. Frontiers in physiology, 5, 522. doi:10.3389/fphys.2014.00522.  Tricarboxylic acid cycle (TCA cycle) Acetyl-CoA (two-carbon) then enters the TCA cycle, where it attaches to a four- carbon compound, oxaloacetic acid (OAA) to form citric acid/citrate (six- carbon) – Citric acid cycle, Krebs cycle. Citrate is then converted to isocitrate, then to succinyl-CoA and then to alpha- ketoglutarate. The formation of alpha-ketogluterate produces NADH, as does the next reaction to succinyl-CoA also produces NADH. Succinyl-CoA then forms fumarate in a reaction that produces an FADH2. Fumarate then forms malate, and then malate forms OAA again, with the production of another NADH. So the net effect of the TCA cycle from one Acetyl-CoA is to produce three NADH, one FADH2 and one ATP.  Tricarboxylic acid cycle (TCA cycle) 2C 4C 6C 8 enzymes 6C are involved 4C in TCA cycle! 4C 5C 4C Source: MacLaren, D., & Morton, J. (2012). Biochemistry for sport and exercise 4C metabolism. UK: John Wiley & Sons.  Electron transport chain (ETC) Also known as electron transfer chain and oxidative phosphorylation. Inside the mitochondrion cristae (big area/luas permukaan) for the reactions to occur efficiently. NADH (from glycolysis and TCA cycle) and FADH2 (from TCA cycle) will enter ETC and undergo oxidative phosphorylation to produce ATPs. Each NADH results in the formation of three ATPs via oxidative phosphorylation whilst the FADH2 is re-oxidized to form two ATPs via oxidative phosphorylation. Electron transport chain (ETC) – the concept of oxidation & reduction The basics of electron transfer can be realized in reduction-oxidation - redox reactions in which a molecule. Molecule - when reduced, gains an electron. Once in its reduced form, the molecule needs to become oxidized again to get rid of this electron. Thus, the reduced form of a molecule gains an electron and an oxidized form loses an electron. Previously More modern term Oxidation +O -H - e- Reduction -O +H + e- When NADH is formed from NAD, NADH is the reduced form and the NAD+ is the oxidized form. For NADH to become NAD, it needs to donate an electron to another molecule. If it does so, this other molecule then becomes reduced.  Electron transport chain (ETC) – the process Electron transfer chain occurs when electrons are donated from NADH and FADH2 (with losing of H+ too) along a chain in the inner mitochondrial membrane. These are in effect a series of reduction-oxidation reactions. Involves four complexes (I to IV) that temporarily accept the electron, but then expel it until it meets the final electron acceptor, O2. H+ form a steep gradient in the intermembrane space and tend to come back into the mitochondrion matrix through the enzyme ATP synthetase (door) – create a great force – for the enzyme to work (joining ADP and Pi to form ATP).  Electron transport chain (ETC) - structure Important elements in this structure Complex Real name e- e- I NADH-Q e- e- reductase e- e- II coenzyme-Q ATP synthetase III cytochrome reductase e- IV Cytochrome C and cytochrome oxidase ATP synthetase iron-containing molecules - iron deficiency in the human body - impair aerobic energy production. Source: MacLaren & Morton, J. (2012). Electron transport chain (ETC) – Oxidative phosphorylation Mitochondrion matrix Final electron receptor ATP synthetase (door) ADP + Pi ATP phosphorylation A great force/ energy is formed & used! (Source: https://www.shutterstock.com/sear ch/cartoon+door; ATP synthetase (door) https://favpng.com/png_view/cart oon-children-cartoon-child- illustration-png/zHsBhV0V)  Calculation of ATP generated in one glucose oxidation Glycolysis - net production of two ATPs and two NADH molecules. ‘link’ reaction (conversion of pyruvate to acetyl-CoA) produces a further two NADH, don’t forget you have two pyruvates generated from one glucose in glycolysis, so you will have two acetyl-CoA to enter TCA and ETC. TCA and ETC – 3 NADH, 1 FADH2, 1 ATP. Don’t forget you have two acetyl-CoA molecules from two pyruvates. 1 NADH when oxidized can generate 3 ATPs. 1 FADH2 when oxidized can generate 2 ATPs. Calculation of ATP generated in one glucose oxidation 2 “link” reaction 2 + ETC Sources of ATP - Primary energy sources (to generate ATPs) for different running distances ATP storage 3s 8-10s Glycogenolysis and Tricarboxylic acid cycle glycolysis (TCA) and Electron Transport Chain (ETC) 90s Several hours or more We survive!  Question? Now, can you explain why O2 and water are so important for our survival?  Next Some general knowledges of prolonged/endurance exercise related to the body carbohydrate (CHO) metabolism  Endurance exercise on carbohydrate metabolism Endurance exercise - defined as prolonged steady-state exercise performed for durations between four minutes and four hours. Middle distance events (e.g. track cycling, rowing, and swimming). Long distance events (e.g. marathon running) and extended stages of road cycling such as those of the Tour de France (‘Ironman triathlons’ - ultraendurance). (Sources: https://www.cartoonstock.com/directory/m/marathon.asp) Endurance exercise related to carbohydrate metabolism Increasing exercise intensity increases CHO utilization (from both muscle glycogen and blood glucose) and reduces lipid oxidation (from both plasma FFA and IMTG). Increased CHO utilization with increasing exercise intensity is due to post- transformational allosteric regulation of phosphorylase and transformation of PDH (pyruvate dehydrogenase). Increasing exercise duration increases lipid oxidation but reduces CHO oxidation, as reflected by reduced glycogen and blood glucose utilization. Carbohydrate loading is simply a nutritional strategy to increase the glycogen stored in your body above its normal amount. This typically involves several days of eating more CHO than usual while also decreasing exercise to reduce the amount of CHO you are using. Endurance exercise related to carbohydrate metabolism CHO-loading increases muscle glycogen concentration and utilization during exercise due to increased phosphorylase activity as a result of increased substrate provision. Increased pre-exercise muscle glycogen concentration increases PDH activity and vice versa. Reduced CHO oxidation following training is due to reduced glycogenolysis (in turn regulated by reduced allosteric modulation of phosphorylase) and PDH activity (likely due to reduced pyruvate production). Liver glycogenolysis is reduced following training, as is muscle glucose uptake. The main cause of fatigue in prolonged endurance exercise is likely reduced muscle glycogen and blood glucose availability, which reduces the availability of substrate required to maintain the high CHO oxidation rates necessary to sustain high power outputs.  Next Some general knowledges of high- intensity intermittent exercise (HIE) related to the body carbohydrate (CHO) metabolism (Source: https://www.123rf.com/p hoto_21157975_vector- illustration-of-cartoon- rugby-player.html)  HIE related to carbohydrate metabolism High-intensity intermittent exercise (HIE) is characterized by brief periods of high-intensity activity (near maximal or supra-maximal) interspersed with periods of low- to moderate intensity exercise or periods of inactivity (i.e. rest). Eg. soccer, rugby, basketball. Energy production during HIE may be fuelled by both anaerobic (PCr hydrolysis, adenylate kinase, anaerobic glycolysis) and aerobic metabolism of both carbohydrate and lipids. It is a common misconception that “anaerobic metabolism” is the most important energy producing pathway during HIE. Indeed, “oxidative phosphorylation” becomes more important to ATP turnover with each successive bout of high-intensity interval exercise and, in some cases, is the main contributor to ATP production.  HIE related to carbohydrate metabolism CHO ingestion prior to HIE augments plasma insulin, glucose and CHO oxidation and suppresses plasma glycerol, FFA and lipid oxidation. CHO ingestion during HIE may spare muscle glycogen utilization, maintain CHO oxidation rates and improve exercise capacity. In the context of prolonged HIE that is relevant to sport, fatigue may be related to depletion of substrates such as glycogen and PCr, especially in type II fibres.  Thank you https://obe.ums.edu.my/obe/courseCOPO_att_link.aspx?id=248070&id2=23621 &pass=49D9820F-A1C3-4387-89DA-F76D54ED95B9 Please log into iTEL, PC30103 Sem 1_2024-2025 for PC30103 Assignment 1 for Lecture 3. 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