MCS - Metabolism Study Materials

What is Catabolism ? the breakdown of complex molecules in living organisms to form simpler ones, together with the release of energy; destructive metabolism. - Food is broken down into energy and waste products - Molecules are broken down into ATP + Heat - synthesis and break down of proteins and lipids are linked to glucose catabolism Describe the Cori Cycle ? - Glucose in the muscle breaks down into pyruvate - The pyruvate then separates into Lactate and Alanine - Lactate is released from tissue, transported to liver, and converted back to pyruvate - The pyruvate in the liver is converted back to glucose which travels in the blood to the muscles. Describe the metabolic interchange between the liver and the kidney ? Describe the Urea cycle ? - Only takes place in liver - Detoxification - Irreversible = has 2 ATP consuming steps - Maintain Urea & Ammonia ratio at 500:1 - Ammonia is processed to reduce its toxicity What happens during the Urea cycle ? Describe Gluconeogenesis ? - it occurs in the liver and kidneys - it is a metabolic process by which organisms produce sugars (glucose) for catabolic reactions from non-carbohydrate precursors - synthesizing glucose out of amino acids 1/9 and non-hexose carbohydrates (commonly pyruvate) - reverse of glycolysis - Pyruvate is converted into oxaloacetate by pyruvate carboxylase - it cannot pass through the mitochondria membrane = it must first be converted into malate by malate dehydrogenase - Malate crosses mitochondria memDescribe the process of gluconeogenebrane into cytoplasm and is converted sis ? back into oxaloacetate - Oxaloacetate is converted to phosphoenolpyruvic acid - phosphoenolpyruvic acid is converted into Fructose - Fructose is then converted to Glucose What is the link between the Cori cycle Pyruvate formed during glycolysis is conand glycolysis ? verted to glucose. Alanine = Pyruvate Aspartate = Pyruvate - Oxaloacetate Phenylalanine, Tyrosine, Tryptophan = Phosphoenolpyruvate & Erythrose 4-phosphate What are the precursors of amino acids in glycolytic pathway ? Glycolytic pathway = Lipids are Brocken down into Glyceraldehyde-3-phosphate Identify molecules in the glycolytic pathKrebs cycle = Fatty acids are broken way and Krebs cycle that are derived down via a process called Beta-oxidation from fatty acids. in the matrix of the mitochondria, into acetyl CoA What is Glycolysis ? The breaking down of glucose Describe glycolysis ? 1 - Glucose is converted into fructose 1,6-bisphosphate 2 - Cleavage of the Fructose 1,6- bisphosphate into two 3-carbon fragments 3 - ATP is harvested when the 3-carbon fragments are oxidised to pyruvate. 2/9 Catalyses the transfer of the phosphoryl What is the role of the Hexokinase engroup from ATP to the hydroxyl group on zyme in Glycolysis ? carbon 6 of glucose. Catalyses the phosphorylation of FrucWhat is the role of the Phosphofructokitose-6-phosphate to Fructose-1,6-bisnase enzyme in Glycolysis ? phosphate by ATP. Catalyses the transfer of a phosphoryl What is the role of the Pyruvate kinase group from phosphoenolpyruvate (PEP) enzyme in Glycolysis ? to ADP. What is the glycolytic pathway ? A series of enzyme catalysed reactions that lead to the formation of metabolic energy in the form of ATP & reduced co-enzyme NADH. - Initially = increases the rate of glycolysis How would increasing the concentration - It is an allosteric inhibitor of Hexokinase of Glucose-6-phosphate affect the net = high concentrations can inhibit glycolrate of glycolysis ? ysis by decreasing the entry of glucose into the pathway It increases the rate of glycolysis: How would increasing the concentration - it raises the levels of substrates for of Fructose-1,6-bisphosphate affect the all subsequent reactions in the glycolytic net rate of glycolysis ? pathway. It is a feedback inhibitor of phosphofrucHow would increasing the concentration tokinase-1 of Citrate affect the net rate of glycolysis - Increasing the concentration of citrate ? decreases the rate of glycolysis The cell no longer requires glucose: - For energy What does high concentrations of Glu- For storage in the form of glycogen cose-6-phosphate signal ? - As a source of biosynthetic precursors The glucose will be left in the blood Provides Glucose-6-phosphate for : What does Glucokinase do ? (Hexoki- - Synthesis of glycogen nase) - A storage form of glucose used for formation of fatty acids. 3/9 - It is inhibited allosterically by high conHow is phosphofructokinase inhibited? centrations of ATP that lower its affinity for fructose-6-phosphate AMP How is the inhibitory action of ATP over- - the phosphofructokinase activity income ? creases when the ATP/AMP ratio is lowered. Where is the L-type isozyme of pyruvate kinase found ? In the Liver Where is the M-type isozyme of pyruvate kinase found ? In the muscle and brain How is Pyruvate Kinase inhibited ? - ATP allosterically inhibits L and M forms of pyruvate kinase to slow down glycolysis when the energy charge is high - Alanine allosterically inhibits pyruvate kinases to signal that building blocks are abundant. What is Beriberi ? - Neurologic and cardiovascular disorder caused by a dietary deficiency of thiamine (vitamin B1) . - the levels of pyruvate and ±ketoglutarate in the blood are higher than normal (especially after ingestion of glucose) What is a reliable diagnostic marker of - Low transketolase activity of red blood Beriberi ? cells - People addicted to alcohol (poor diet) - Women who have extreme nausea and vomiting in pregnancy What types of people does Beriberi nor- People suffering from AIDS (use of dimally occur in ? uretics and diarrhoea) - After Bariatric surgery (dietary deficiencies) - Hexokinase - Phosphofructokinase - Pyruvate kinase What are the catalytic steps in the glycolytic pathway catalysed by ? 4/9 What is the Krebs cycle? second stage of cellular respiration, in which pyruvic acid is broken down into carbon dioxide in a series of energy-extracting reactions - Citric acid cycle - Tricarboxylic acid cycle - aerobic process = requires to oxygen to form NAD+ to keep the cycle going - 2 Carbons in : 2 Carbons out - Oxaloacetate (4C) condenses with acetyl CoA forming citrate = this reaction is catalysed by citrate synthase - Two carbons enter the cycle as Acetyl CoA Describe the steps in the Krebs cycle ? - Two carbons leave the cycle as two molecules of CO2 Molecules produced by the Krebs cycle: - Three molecules of NADH - One molecule of FADH2 - One molecule of GTP - CO2 = released as a waste product - High energy electrons = in the form of NADH What are the major end products of the - the high-energy electrons from NADH Krebs cycle ? are passed to the electron transport chain to combine with O2 to produce H20. - because there is no other efficient way for the NADH to get rid of its electrons Why does the Krebs cycle require O2 ? and regenerate NAD+ that is needed to keep the cycle going. By allosteric enzymes: - isocitrate dehydrogenase - ±ketoglutarate dehydrogenase How is the Krebs cycle regulated? - it is allosterically stimulated by ADP = What is the role of the Isocitrate dehydroenhances the enzymes affinity for subgenase enzyme in the Krebs Cycle ? states 5/9 - NADH = by displacing NAD+ (it binds in How is isocitrate dehydrogenase inhibitthe place of NAD+) ed ? - ATP - inhibited by its catalytic products = succinyl CoA and NADH How is ±ketoglutarate dehydrogenase in- High energy charge = the rate of the hibited ? Krebs cycle is reduced when the cells has a high concentration of ATP. At what step during the enzyme-catalysed steps of the tricarboxylic acid cycle - Occurs at the Krebs cycle step cataldoes the Net incorporation of water oc- ysed by citrate synthase cur ? At what step during the enzyme-catal- Aconitate = hydrated to form isocitrate ysed steps of the tricarboxylic acid cycle - Fumarate = hydrated to form malate does Two hydration reactions occur ? ketoglu- Isocitrate = converted to a ±At what step during the enzyme-cataltarate ysed steps of the tricarboxylic acid cycle - ±ketoglutarate = converted to succinyl is CO2 released ? CoA Name one intermediate that cannot be Isocitrate cannot be removed from the added or removed by other metabolic citric acid cycle to be used by other metapathways in the Krebs cycle ? bolic pathways. - It is transported out of the mitochondria How is Citrate used in metabolic pathto be used as a source of cytoplasmic ways other than the TCA cycle ? acetyl CoA. How is Fumarate used in metabolic path- - produced during phenylalanine and tyways other than the TCA cycle ? rosine degradation. How is ±ketoglutarate used in metabolic pathways other than the TCA cycle ? Can be formed from glutamate Can be produced by pyruvate decarHow is Oxaloacetate used in metabolic boxylase and is used during gluconeogepathways other than the TCA cycle ? nesis. What happens to the Citric acid cycle - increases the production of Acetyl CoA when Coenzyme A concentration is infrom pyruvate and the amount of pyrucreased ? 6/9 vate entering the cycle - Increases the rate of the cycle If the initial [Acetyl CoA] is low and increased: - it increases the rate of the condensation reaction that is catalysed by citrate synthase - this leads to formation of citrate If [Acetyl CoA] becomes too high: - it can inhibit dihydrolipoamide acetyltransferase (E2), its a component of the pyruvate dehydrogenase complex - leads to a decrease in the concentration of acetyl CoA formed from pyruvate. = rates of the reaction of the citric acid cycle would be decreased What happens to the Citric acid cycle when Acetyl CoA concentration is increased ? - increase the rate of the cycle because this oxidised cofactor interacts with lots of enzymes in the citric acid cycle - NAD+ activates the dihydrolipoamide What happens to the Citric acid cycle acetyltransferase (E2) of the pyruvate when NAD+ concentration is increased dehydrogenase complex ? - it is a cosubstrate of isocitrate dehydrogenase, malate dehydrogenase and ketoglutarate dehydrogenase E3 of the ±complex and the pyruvate dehydrogenase complex. - Last step in the degradation of glucose to release a major portion of its chemical energy - Electron carriers NADH& FADH2 transWhat is the Electron Transport Chain ? fer the electrons that they have gained when oxidising other molecules to the ETC embedded in the inner membrane of the mitochondrion Where is the electron transport chain located? 7/9 Inner mitochondrial membrane How are high energy electrons moved through the electron chain ? Protein carriers move high energy electrons from NADH and FADH2 along the chain of proteins and pump in proteins from the mitochondrial matrix to the intermembrane space. What happens as the electrons move along the chain ? - they fall to successively lower energy states - energy that the electrons release in this process is used to move protons across the membrane from the inner mitochondrial space (matrix) to the outside (intermembrane space) - H+ ions gradient is generated - Gradient serves as a source of energy that can be used by ATP synthase to add a phosphate group to ADP to produce ATP. O2 combines with a hydride ion to produce water a waste product of metaboWhat is the role of Oxygen in the ETC ? lism - it is the terminal electron acceptor Describe ATP synthase ? - It consists of two multi-subunit components F0 and F1 - Which are linked by a slender stalk - spans the lipid bilayer, forming a chanExplain the F0 part of ATP synthase ? nel through which protons can cross the membrane. Harvests the free energy derived from proton movement down the electrochemExplain the F1 part of ATP synthase ? ical gradient by catalysing the synthesis of ATP. How is the ETC regulated ? By Phosphorylation - ADP levels - concentration of ADP is the most important factor for determining the rate of oxidative phosphorylation - Unless ADP is Phosphorylated to ATP 8/9 electrons do not usually flow through the ETC to O2 - Oxidative phosphorylation is coupled to the consumption of ATP - 2,4-DNP electron from NADH to O2 is not disrupted - ATP is not formed by mitochondrial ATP synthase - this is because the proton-motive force What happens when oxidative phosphoacross the inner mitochondrial memrylation is uncoupled ? brane is dissipated - leads to increased oxygen consumption and oxidation of NADH - No energy is stored as ATP - Energy is released as HEAT !! An antidote to cyanide poisoning is nitrite that converts oxyhemoglobin to Methemoglobin. Methemoglobin competes with cytochrome a3 for cyanide. Explain why this treatment for cyanide poisoning is effective ? - Cyanide binds to Fe3+ of cytochrome a3 - Methemoglobin is an effective antidote as it also contains an Fe3+ tat completes with cytochrome a3 for binding to cyanide. 9/9