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  1. 1. MetabolismIntroduction to Metabolism1. Define metabolism12. What are the endings for processes involving catabolism and anabolism respectively?23. Are ATP and NADH used in anabolic or catabolic processes?34. Name the umbrella terms for the pathways used to convert the following into Acetyl CoA: Glucose, Fatty acids, Amino acids45. Whereabouts does b-oxidation of fatty acyl CoA into acetyl CoA occur? 56. What is the name of the enzyme which converts pyruvate into Acetyl CoA 67. What are the three components of an ATP molecule?78. What does hydrolysis mean?89. What are the two main uses of ATP in the human body?910.What is an allosteric enzyme? 10Glycolysis1. Where does glycolysis occur?112. Name all 4 stages of glycolysis121 Series of enzyme reactions within cells for converting fuel molecules into ʻuseful energyʼ2 Catabolic processes (breakdown) end in ʻlysisʼ e.g. glycolysis, Anabolic processes end in ʻgenesisʼ3 Anabolic, NADH is used to add H+ and ATP used to add phosphate4Glucose is converted into pyruvate and then Acetyl-CoA by glycolysis, Fatty acids into Acetyl-CoA by betaoxidation and Amino acids by transamination5In the mitochondria, it is transported there by carnitine6Coenzyme A7 Ribose sugar, adenine unit, 3 phosphate chain8 Cleavage of chemical bonds by the addition of water9 Na/K ATPase and Muscle contraction10 Multiple binding sites. Enzyme changes shape on binding (other than active site) which allows regulation11 Cytosol12 Investment/Activation Stage, Splitting of 6C into 2x 3C, Oxidation Step, ATP Synthesis (x2)
  2. 2. 3. Name all 10 products in glycolysis134. What enzymes are used at each stage? 145. Which steps use ATP and give off ADP?156. Which steps synthesise ATP from ADP?167. In situations of oxygen depravation, what happens to excess pyruvate which cannot be converted into CO2?178. In the presence of oxygen, in human tissue, pyruvate is converted into?189. Rate of glycolysis is at its highest under what conditions?1910. Rate of glycolysis is lowest under what conditions?2011. Which step is targeted by an allosteric protein/enzyme to inhibit the metabolic pathway? 2112. If pyruvate is converted into lactate in the muscles, where does the reverse occur?2213. What is the enzyme used to catalyse the conversion of pyruvate into lactate? 2314. Why do RBC undergo a comparatively large amount of glycolysis?24Glycogen Synthesis & Degradation13Glucose, Glucose 6 phosphate, Fructose 6 phosphate, Fructose 1,6, phosphate (Activation Stage)Dihyrdoxyacetate phosphate, Glyceraldehyde 3 phosphate (Splitting of 6C to 3C), 3 Biphosphoglycerate,(oxidation step) 3 phosphoglycerate, 2 phosphoglycerate, phosphoenolpyruvate, pyruvate (ATP Synthesis)14 Hexokinase, Phosphoglutonate isomerase, phosphofructokinase, fructose biphosphate aldolase,triphosphate isomerase, glyceraldehyde phosphate dehydrogenase, phosphoglycerate kinase,phosphoglycerate mutase, enolase, pyruvate kinase15 Glucose to Glucose-6-phosphate, Fructose 6 phosphate to fructose 1,6, diphosphate16 3 Biphosphoglycerate to 3 phosphoglycerate, Phosphenolpyruvate to pyruvate17 Pyruvate is converted into lactate (a.k.a. lactic acid)18 Acetyl CoA19 During exercise or after high carb meal (high levels of insulin)20Fasting state - because there are high levels of circulating glucagon. Glucagon converts glycogen intoglucose but also inhibits glycolysis via the 2nd ATP using step in the activation stage21Within the activation stage, phosphofructokinase which converts fructose-6-phosphate into fructose 1-6-biphosphate can be inhibited to slow metabolism22 Lactate can be converted back into pyruvate in the liver23 Lactate dehydrogenase, because NADH is returned to NAD+ (dehydrogenated)24 Because they donʼt contain mitochondria so cannot use TCA cycle/ETC
  3. 3. 1. What are the respective weights of blood plasma glucose and glycogen stores in the body of a typical 70kg adult252. What is the pathway for conversion of glycogen into glucose in the blood?263. What configuration of glycoside links connect glucose monomers in a straight chain of glycogen and what form the branch junctions?274. Which enzymes are associated with forming these bonds? 285. What is the reaction pathway which transfers glucose into the first glucose-protein primer which kickstarts glycogen formation?296. How is glycogen synthase activated and deactivated?307. How is glycogen phosphatase activated and deactivated? 318. Which hormone stimulates release of protein phosphatase and so glycogen buildup?329. Which hormones stimulate release of protein kinase and so glycogen breakdown?3310.Name the diseases associated with defective glucose-6-phosphate, lysosomal glycosidase and glycogen phosphorylase.34Aerobic Respiration1. What are the respective pathways for obtaining acetyl-CoA from: glucose, fatty acids and amino acids?3525 10g glucose in blood plasma, 120g glycogen stored in liver, 400g in muscle26 Glycogen--> Glucose 6 phosphate --> Glucose27 1,4 glycosidic bond are the chains, 1,6 glycosidic bonds make the branches28 Glycogen synthase for straight 1,4 bonds, branching enzyme for 1,6 branch junctions29 Glucose ---> glucose-6-phosphate ---> glucose-1-phosphate ---> UDP glucose30Activated by protein phosphatase cleaving a phosphate, deactivated by protein kinase and ATP adding aphosphate31Activated by protein kinase & ATP adding a phosphate, deactivated by protein phosphatase removingphosphate32 Insulin (secreted by pancreas, acts in liver, muscle and fat tissue)33Glucagon (secreted by pancreas, acts in liver only), Adrenaline (secreted by adrenal gland, acts in muscleand liver)34Von Gierkeʼs = glucose-6-phosphatase, Pompeʼs = lysosomal glycosidase, McArdleʼs = glycogenphosphorylase35 Glucose = glycolysis to pyruvate and then acetyl CoA, fatty acid beta oxidation, amino acids bytransamination
  4. 4. 2. Which unit out of glucose, fatty acids or amino acids produce the most acetate molecules per molecule of themselves and therefore highest energy per unit weight? 363. Is acetyl CoA reduced or oxidised during the TCA cycle? 374. Where does the TCA cycle take place within the cell/organelles?385. Why do red blood cells not make extensive use of the TCA cycle for respiration?396. How many carbons are there in acetyl-CoA? 407. Name all 9 compounds which are the subject of the TCA cycle in order418. Which steps produce CO2 having cleaved it off the molecules involved?429. What is the name for a chemical pathway which cleaves a bond due to the addition of water? (e.g. conversion of malate into oxaloacetate)4310.What is the function of coenzyme A in the citric acid cycle?4411.What part of the coenzyme A molecule is the active bit in this reaction and what type of bonds does it form? 4512.Which steps produce NADH from NAD+ during oxidation of compounds involved? 4613.How many carbons are there in succinyl-CoA 4714.Which reaction step produced GTP? 4836 Fatty acids37 oxidised to produce CO2 and H2O38 in the mitochondrial matrix39 RBC contain very few mitochondria40 241 Acetyl-CoA, Citrate, isocitrate, alpha ketoglutarate, succinyl CoA, succinyl, fumarate, malate, oxaloacetate42 Isocitrate to alpha ketoglutarate and alpha ketoglutarate to succinyl CoA43 hydrolysis44 Oxidation of pyruvate to form acetyl CoA45The ʻSHʼ at the end of the Coenzyme A forms thioester bonds with carboxylic acids (e.g. citric acid). TheCoA on acetyl CoA is a thioester bond. (thiol = sulphur-carbon compound)46 Isocitrate to Alpha-Ketoglutarate, Alpha-Ketoglutarate to Succinyl-CoA and Malate to Oxaloacetate47 4, with citrate having lost two to CO2 during an earlier step48GDP and Pi are converted into GTP (a similar compound to ATP) in the step between succinyl CoA andsuccinate
  5. 5. 15.Which reaction step produces FADH2 from FAD during an oxidation reaction? 4916.Where is the electron transport chain?5017.Roughly how many ATP are synthesized per molecule of NADH in the ETC?5118.Which side is more acidic, the mitochondrial matrix or inter-membrane space? 5219.What are the proton pumps powered by? 5320.How many ATP are produced by glycolysis and TCA cycle respectively? 5421.Which steps in the TCA cycle are irreversible? 5522. Which substances can be produced by transamination?5623.How many ATP are effectively produced by the products of the TCA cycle?57Fat as Fuel1. Name the functions of lipids/sterols in the cell membrane582. Where do triglycerides get their name from? 593. What is the typical weight of fat at triglyceride on a 70kg adult? 6049 Succinate to fumarate50 Proteins on the inner mitochondrial membrane51 Around three molecules of ATP are synthesized per molecule of NADH in the electron transport chain52A proton gradient is generated by proton pumps on the inner membrane, these pump H+ (protons)released by oxidation in the TCA cycle out of the mitochondrial matrix (inside the mitochondria) into the inter-membrane space. This makes the inter-membrane space more acidic and leaves the matrix more alkaline53 Release of energy (electrons) from NADH to NAD+54 Net yield of 2 ATP in glycolysis and 10-12 from TCA cycle55 Isocitrate dehydrogenase, ketoglutarate dehydrogenase and citrate synthetase56Transamination of amino acids can produce either alpha ketoglutarate (from glutamate/glutamine) oroxaloacetate (from aspartate)57 Per Cycle = (1 GTP = 1 ATP, 3NADH = 2.5, 1 FADH2=1.5)x2 = total 10 ATP58 Phospholipids and cholesterols in the membrane are precursors of hormones. Protein complexes maycleave off parts of these lipid molecules which become second messengers in the cell.59 Because they contain 3 fatty acids (tri) attached to a glycerol molecule60 Around 11kg stored as triglycerol fat droplets
  6. 6. 4. In order, which of the following produces the most energy per weight basis and which is the least? And why? Fatty acids, glucose and amino acids 615. Name 3 common fatty acids626. Out of these, which are saturated and which are unsaturated? 637. Why do double bonds in unsaturated fatty acids make membranes more fluid?648. What is an ester bond? 659. Describe the series of breakdown steps to turn triacylglycerol into building blocks which are free to travel in the blood? 6610.What types of enzyme are used in this breakdown reaction?6711.What protein do individual fatty acids bind to to travel in the bloodstream? 6812.What it the name of the process for converting glyerol (glycerol not glycogen) into glucose in the starvation state? 6913.Where does glycerol enter glycolysis under normal conditions in most tissues? 7014.Whereabouts in the cell/organelles does fatty acid beta oxidation take place? 7161Fat produces the most, followed by protein, and carbohydrate the least. The reason is that fats are morereduced than protein and carbs. (i.e. fats have more H+ contained within them, ʻsaturatedʼ with H)62 Any of palmitic acid, stearic acid, oleic acid linoleic acid or linolenic acid63 palmitic and stearic acid contain no double bonds, oleic = 1, linoleic = 2, and linolenic = 364 Because the double bonds make a ʻkinkʼ in the physical shape of the molecule, so the membrane is not astightly packed and easier to squeeze through65An ester is a compound containing a carbonyl (a carbon double bonded to an oxygen) bonded to an ether(an oxygen molecule next to two alkylʼs) (alkyl = a saturated hydrocarbon)66 Triacylglycerol-->(fatty acid given off)-->diacylglycerol---> (fatty acid given off)--->monoacylglycerol-->(fatty acid given off)-->glycerol. The 3 fatty acids and glycerol as separate products are freely diffusible in thebloodstream67 Lipases68 Albumin69In conditions of starvation (when glucagon inhibits glycolysis) glycerol from triglyceride breakdown can beconverted into glucose for used in glycolysis by the process of gluconeogenesis.70 Converted into pyruvate in glycolysis then enters the TCA cycle71 In the mitochondrial matrix (fully inside the mitochondria, inside both membranes of the double membrane)
  7. 7. 15.Where/how do fatty acids (not glycerol) enter the metabolism pathway (i.e. glycolysis/ TCA and which step)? 7216.What substance does fatty acyl-CoA couple with to enter the mitochondrial membranes?7317.What four reactions are the core of B-oxidation?7418.If a carbon-carbon double bond is added to a compound during a reaction step what type of reaction is this likely to be?7519.Name the products of the degradation of fatty acyl-CoA into acetyl-CoA 7620.How many repeats of the B-oxidation pathway will a fatty acid with 24 carbon atoms pass through and how many acetyl CoA molecules will be generated before the fatty acid is completely broken down? 7721.If a particular fatty acid produces 10 acetyl-CoA molecules, how many ATP are produced from metabolism of this molecule? 7822.The lipase enzyme which breaks down fatty acids is activated by which substances? 7923.How is fatty acid metabolism regulated other than by these substances? 8024.Which organ in the body relies almost entirely on glucose for fuel (and hence cannot metabolize fat, which goes direct to acetyl-CoA)81Skeletal Muscle: Regulation of contraction72Although citrate (6c) can be converted into fatty acids if needed, fatty acids may only enter the TCA cyclevia acetyl CoA. Fatty acids are converted into fatty acyl CoA by activating enzyme using ATP to AMP and PPi73 Carnitine74 Removal of 2H atoms, addition of water, removal of 2H atoms and removal of 2C unit75 An oxidation reaction because oxidation is loss of H+76 Fatty acyl CoA (chain) --> Enoyl-CoA --> 3-L-Hydroxyacyl-CoA --> B-ketoacyl-CoA --> Fatty acyl CoA(remaining chain) and Acetyl CoA (2C unit which enters TCA cycle)77 Because a 2C unit is cleaved with each cycle it will take 11 cycles of B-oxidation to fully break down thefatty acid, a 2C unit will be remaining at the end of the 11th cycle so there will be 12 acetyl CoA (2C) unitsproduced in total78 11 acetyl CoA = 10 repeats of the TCA cycle (10x11=110 ATP). As far as beta oxidation is concerned, 10NADH (2.5 ATP x 10 = 25) and 7 FADH (1.5 ATP x 10 = 15) are produced per cycle so 150 ATP in total79 adrenaline and glucagon, these are released when the body needs energy80 Rate of entry into mitochondria (via carnitine shuttle) and rate of reoxidation of NADH and FADH281 The brain, only glucose can cross the blood-brain barrier
  8. 8. 1. What are the three main stages involved in controlling muscle contraction from AP in axon hillock to muscle movement? 822. What is the name of the main neurotransmitter at the neuromuscular junction of skeletal muscle?833. What is the first thing that happens when Acetylcholine binds to nicotinic receptors on the post synaptic membrane? 844. What features of the muscle fibre allow the AP to dive into the centre of the fibre?855. What happens when the AP reaches a ʻtriadʼ in one of these features? 866. What is the difference between an electrotonic potential and an action potential? 877. How does relaxation of the muscle occur?888. What causes bound troponin to change its shape and initiate muscle contraction? 899. Name the three troponin subunits, which one does calcium bond to? 9010.Why is the twitch in skeletal muscle much longer than the AP which triggered it? 9182 CONDUCTION - AP set up in axon hillock of a motor neuron and propagated along the axon to itstermnals, NEUROMUSCULAR TRANSMISSION - chemical transmission at the neuromuscular junction toset up an AP in the muscle fibres, EXCITATION-CONTRACTION COUPLING - process by which muscle APcauses rise of intracellular Ca2+ and actin-myosin interaction83 Acetylcholine84Causes opening of integral cation channel, leading to Na+ influx resulting in a local depolarisation calledend plate potential, this causes an action potential which moves along the muscle fibre away from the NMJ85 T-tubules86When the AP reaches a ʻtriadʼ, it is detected by voltage sensors which cause calcium release channels inthe sarcoplasmic reticulum to open. Calcium leaves the SR. Calcium ions bind to the thin filament allowingthe 3rd stage (cross bridge cycling) to start.87Electrotonic potentials rely on charge diffusion across a wide area of the cell away from the Na+ gatewhere the potential originates from. In an action potential, voltage gated ion channels are used which takeslonger and uses energy but allows the potential to cover a long distance.88 When the Calcium ions are pumped back into the sarcoplasmic reticulum89Release of calcium from the SR which binds to troponin when in high concentration and changes itsconfiguration. This moves the tropomyosin out of the way so myosin can bind to actin filaments.90 Tnl, TnC and TnT, Ca2+ binds to TnC91 Time is needed for various steps to occur which do not occur in the AP (e.g. SR Ca channels to open andCa to diffuse out, Ca to bind to troponin TnC subunit and change troponin configuration allowing crossbridges to start interacting with thin filaments and physical tightening of elastic structures,
  9. 9. 11.What are the relative lengths of time taken to twitch by a short twitch and long twich fibres?9212.Why do fast fibres shorten faster than short twitch fibres?9313.What types of muscle fibre would be most common in (i) a marathon runner and (ii) a sprinter?9414.What is a tetanus? 9515.Apart from short and long twitch, how else might types of muscle fibres be classified? 9616.Out of training for endurance, strength or speed which is the least effective in terms of recruitment of specific kinds of muscle fibre?9717.How do muscle fibres adapt to an increase in length?9818.What happens to muscle fibres when they are regenerating after damage?99Nutrition and Health1. What makes a fatty acid or amino acid ʻessentialʼ in the diet? 1002. Which of the following only contains one dietary component (macronutrient)?: Egg, pasta, beef, cake, butter, champagne 1013. What are the main factors considered in the creation of Dietary Reference Values? 10292 Short twitch = 0.12s, long twitch = 0.32s93They have a faster ATPase which allows them to repolarise quicker and get through more cross bridgecycles per second94 Marathon runner would have mainly slow twitch and a sprinter mainly fast twitch95 When a group twitches occur in such quick succession that they overlap96 By how they generate most of their ATP, aerobic/oxidative (slow) vs glycotic/anaerobic (fast)97Strength can be improved by increasing muscle hypertropy and cross sectional area in training, endurancecan be improved by increasing oxidative metabolism by increasing capillary supply and number ofmitochondria. Speed, however is difficult to train for as it is hard to alter the proportion of fast muscle fibres.98 Adding (if longer) or deleting sarcomeres (if shorter) to maintain ʻoptimumʼ sarcomere length at new length99Satellite cells are activated and begin to divide, fusion of daughter ʻmyoblastʼ cells and synthesis of newfibre.100 Those which cannot be synthesized in metabolism (e.g. alanine can be synthesized from pyruvate in theTCA cycle101 Butter (only contains fatty acids)102Look at intake of substance in people with no deficiency vs with deficiency, intakes that would cure clinicaldeficiency and (low) intakes associated with a marker of nutritional adequacy (enzyme saturation and tissueconcentration)
  10. 10. 4. What do the DoH recommend as a safe intake for the population?1035. What is meant by reference nutrient intake (RNI)?1046. Why is the EAR recommended for energy intake rather than the RNI?1057. Approximately what percentage of hospital patients are malnourished? 1068. What percentage of the UK population is overweight or obese and what percentage are obese? 1079. In the last 20 years, UK obesity has increased by what percentage?10810. What percentage of children in the UK eat 5 portions of fruit & vegetables per day? 109Liver Function 1: Glucose Homeostasis1. What is the physiological circulating blood glucose in a healthy adult? 1102. What are the consequences of high blood glucose over an extended period? 1113. How many ATP are produced from a single molecule of glucose (net)?1124. What synthetic reactions (synthesis of..) use glucose as a source of a pentose sugar? 1135. How does glucose cross cell membranes and the blood brain barrier?1146. Give a disadvantage of using glucose as a metabolic fuel compared to fatty acids?115103 EAR/RDA plus 2 standard deviations104 The amount that would satisfy 95% of the population i.e. the average plus 2 SD105 Because if someone is already overweight and they consumed the EAR then they would get fatter106 40%107 66% overweight or obese, 25% are obese108 300%109 10%110 3.9-6.7mM111 Dehydration, wasting of body tissue and death112 31113 In particular synthesis of nucleotides and DNA (contain a pentose sugar in structure)114 Diffusion - because it is freely soluble in water, unlike fat and protein115 Glucose produces less ATP per unit weight than fat. Because glucose is freely soluble in water it isosmotically active and can directly damage cells (e.g. diabetic patient having to have limbs amputated)
  11. 11. 7. What is the main function and pathway for glucose metabolism in adipose tissue? 1168. What is the main function and pathway for glucose in erythrocytes (red blood cells)?1179. What is gluconeogenesis?11810.Which enzymes are responsible for the three irreversible steps in glycolysis?11911.Gluconeogenesis bypasses these steps using different enzymes to the glycolysis forward reaction, what are they? 12012.How is gluconeogenesis regulated in terms of enzymes and substrates involved? 12113.What metabolic by-product is transferred between glycolysis and gluconeogenesis in a process known as the Cori cycle?12214.Why is maintaining blood glucose above a certain level crucial to survival? 12315.What do alpha and beta cells in the Islets of Langerhans in the pancreas secrete? 124116The main pathway for glucose metabolism in adipose tissue is glycolysis. The main use of glucose inadipose is not energy production but production of the glycerol, the basis of a triglyceride fat store molecule117 Glycolysis and production of energy, RBC have very few mitochondria so largely rely on anaerobic resp.118 Glycogenesis is a metabolic pathway for the formation of glucose from non-carbohydrate substances(e.g. pyruvate, lactate, glycerol and amino acids but NOT FATTY ACIDS). It is one of the main mechanismsin the human body to stop blood glucose levels from dropping too low during carbohydrate fasting(maintained at 4-5mM/L).119 Hexokinase/Glucokinase (Step 1), Phosphofructokinase (Step 3) and Pyruvate Kinase (Step 10)120 In order (reverse to glycolysis because you are going from pyruvate to glucose):Step 10 uses pyruvate caboxylase enzyme to convert pyruvate into oxaloacetate (using 2CO2, 2ATP and2H20 and giving off 2ADP and 2Pi). Then it uses phosphenolpyruvate carboxylase to convert oxaloacetateinto phosphenolpyruvate (using 2GTP and giving off 2GDP).Step 3 uses fructose 1,6 biphosphatase to convert fructose 1,6,biphosphate into fructose 6 phosphate (usingH20 and giving off 1 phosphate molecule).Step 1 uses glucose 6 phosphatase to convert glucose 6 phosphate into glucose (again using H20 andgiving off 1 phosphate molecule).121 Glycerol (a major substrate in gluconeogenesis) is released from fat breakdown which only happensduring starvation state, so fatty acids can enter the TCA cycle. Muscle protein breakdown in starvation statereleases amino acids (also major substrates of gluconeogenesis). In terms of enzymes, pyruvatecarboxylase (used for converting pyruvate into oxaloacetate) is activated by acetyl-CoA (TCA cycle).122Lactate (lactic acid) is produced after glycolysis in the absence of oxygen (where pyruvate cannot beconverted into Acetyl-CoA). Lactate can be transferred to the liver and is turned back into pyruvate beforebeing broken down into glucose, which is sent back to the tissues. This is known as the Cori cycle.123 Glucose is the only fuel used by the brain; the body needs glucose to respire in anaerobic conditions124 Beta cells secrete insulin, alpha cells secrete glucagon
  12. 12. 16.Out of insulin and glucagon, which is anabolic and which is catabolic? 12517.What are the 4 main metabolic effects of insulin on actions within the liver?12618.What does insulin make the muscle do to glucose?12719.What are the effects of glycogen on adipose tissue? 128Liver Function 2: Protein and Nitrogen Metabolism1. Which of the following three does the body keep least in storage: Glucose, fatty acids, amino acids?1292. All proteins have a certain lifespan (half-life) and so need to be replenished at some point, what is the average protein turnover in a typical adult per day? 1303. What is the nutritional protein requirement for a typical adult per day?1314. Name the essential amino acids (Very many hairy little pigs live in the toilet argentine) 1325. Name three situations in which an individual could have a positive nitrogen balance (protein uptake of body greater than excretion) and three in which someone could have a negative nitrogen balance.1336. Why does the starvation state degrade proteins in the body? 1347. What are the two main component parts of an amino acid?135125Glucagon is catabolic, it promotes breakdown of complex molecules (glycogen) to produce useful fuel.Insulin is anabolic, it promotes the building up of complex glycogen from glucose monomers in the blood.126 Inhibition of glucogenesis, activation of glycogen synthesis, increased fatty acid synthesis, increasedamino acid uptake and protein synthesis127 Increased glucose uptake by increasing glucose transporters (GLUT4)128Increased adipose tissue lipolysis (fat breakdown), increased fatty acid oxidation in the liver (to generatefuel for the TCA cycle)129Amino acids, although freely exchangeable with protein, there are only specific stores in the body forglycogen (glucose storage) and triglycerides (fatty acid storage)130 Around 300-400g of protein per day131 Roughly the same as the individuals body weight in kg but in g (e.g. 50g protein for a 50kg person)132 Valine, Methionine, Histidine, Lysine, Phenylalanine, Leucine, Isoleucine, Threonine, Tryptophan, Arginine133Positive balance = pregnant woman, growing child, convalescence after serious illness, negative balance= starvation, injury and trauma, serious illness.134 Insulin normally inhibits protein breakdown, so in the state of high glucagon levels, proteins are brokendown to provide amino acids which ultimately enter glyconeogenesis and the TCA cycle135 An oxo acid (keto acid) e.g. pyruvate, coupled with an NH2 (amine) group
  13. 13. 8. What happens to an amino acid during the process of oxidative deamination? 1369. What happens to an amino acid during the process of transamination?13710. What is a trans-deamination reaction? 13811. Which is the only amino acid which can be directly deaminated? 13912. What is the difference between ketogenic and glucogenic amino acids? 14013. What substance is excess protein in the liver converted to?14114. Which amino acid can be synthesized during the urea cycle and is therefore not a requirement in the diet of a healthy adult with a neutral nitrogen balance? 14215. What are the four steps within the urea cycle? 14316. The excretion of creatinine is proportional to the mass of what tissue?14417. What is the medical term for impaired conversion of NH3 to urea?14518. What is a normal renal threshold for glucose in mmol/L?14619. What proportion of the population are affected by diabetes and what proportion of the healthcare budget is spent on it? 147136 The amine is split with the acid in the presence of water to produce a keto acid and ammonia (NH3)137 The ketoacid on the amino acid is displaced by a different ketoacid to form an entirely new amino acid138Trans-deamination is a two step process that begins with a transamination reaction which is required tomake an amino acid suitable for deamination. This is the case for degradation of most amino acids exceptglutamine/glutamate, which goes directly to alpha ketoglutamate139 Glutamate/glutamine and aspartate can be directly deaminated140 Ketogenic amino acids can only be degraded into acetyl-CoA whereas glucogenic may become glucose141 Urea142Arginine can be synthesized from carbamoyl phosphate-->citruline-->argininosuccinate(+ATP-->PPi)-->arginine143(1) Carbamoyl phosphate + Ornithine --> Citruline --> (2) Citruline + aspartate --> (3) argininosuccinate ->fumarate (connection with TCA cycle) + arginine --> (4) arginine --> UREA + ornithine144 Muscle145 Hyperammonaemia14610mmol/L (the renal threshold is the blood concentration of a substance above which the substance startsbeing removed in urine, i.e. above 10mmol/L glucose is only incompletely reabsorbed in the PCT)147 3-4% of the population, 5-10% of NHS budget
  14. 14. 20. What is the mechanism of action of ʻearly onsetʼ type 1 diabetes? 148Despoʼs Questions1. What is the function of glucagon? 1492. What processes are activated by insulin?1503. What is glycogen used for and how? 1514. What happens to excess protein taken in the diet?1525. How is blood glucose maintained in fasting? 1536. What is the function of the TCA cycle? 1547. How is glucose oxidised?1558. What are the products of beta oxidation? 1569. Where does it take place?157148 Autoimmune destruction of B-cells, hallmarks are hyperglycaemia (high blood sugar) and ketoacidosis,because ketone bodies are produced in fasting state, dissociated at blood pH and creates lots of H+ ions Released by the body during the fasting state to stimulate breakdown of glycogen stores in the liver and149muscle tissues releasing glucose for energy. Glycogen also inhibits glycolysis.150 Protein & triglyceride synthesis, production of glycogen from glucose.151 Glucose store in liver and muscle tissues, compact, branched structure for rapid metabolism whenneeded but compact are taken up, not osmotically active152Since the body has a relatively small pool of stored amino acid, excess protein is converted either intourea and excreted in the urine, or it may leave the urea cycle as fumarate and enter the TCA cycle.153During the fasting state, glycogen is released which breaks down glycogen stores and releases glucosefrom them. Also breaks down triglyceride stores into fatty acids and glycerol, of these, only glycerol may bebroken down into glucose. Glycogen also inhibits glycolysis, so less glucose is used up by glycolysis andmore stays in the blood.154 Oxidation of Acetyl-CoA and subsequent products to reduce FAD+ to FADH2 and NAD+ to NADH, thesethen produce 2.5 ATP and 1.5 ATP respectively in the electron transport chain which are energy for the body,particularly for muscle contraction and ATPase pumps. One step also makes GTP out of GDP. Also allowsfatty acids and amino acids to be used as energy as they can enter it at various stages.155 Glucose is the starting point for glycolysis, it is oxidised into different compounds beginning withglucose-6-phosphate, fructose-6-phosphate, fructose-1-6-biphosphate etc. reaching Acetly-CoA and goinginto the TCA cycle. Every time the reaction overall gives off H+ in the form of H20, or NADH or FADH2 thereaction is an oxidation reaction. The process of step by step oxidation continues through glycolysis and theTCA cycle.156 Acetyl-CoA from fatty acyl CoA157 Inside the mitochondria, fatty acyl-CoA molecules are transported inside by carnitine