Term
| How is lactate produced and does this occur in both anaerobic and aerobic conditions? |
|
Definition
| Lactate is produced from pyruvate under anaerobic conditions and can be formed from pyruvate even under aerobic conditions as pyruvate and lactate maintain equilibrium. |
|
|
Term
| Where is lactate always produced during cellular respiration and why? |
|
Definition
| Lactate is produced by red blood cells as they don't have mitochondria so even though they carry a large amount of oxygen and are thus considered anaerobic. |
|
|
Term
| What is lactate used for? |
|
Definition
| Lactate can also be used for gluconeogenesis and as a fuel by heart tissue. |
|
|
Term
| What produces large amounts of lactate during high intensity exercise? |
|
Definition
|
|
Term
| What is glycolysis and what is the intermediate molecule? |
|
Definition
| Glycolysis is the process by which glucose is taken and converted into pyruvate via Fructose-1,6-bisphosphate. |
|
|
Term
| How many ATP are required for glycolysis and how many are produced? What is the net gain of ATP? |
|
Definition
| Two ATP are required and four are produced giving a net gain of two ATP. |
|
|
Term
| How many NAD+ are converted to NADH during glycolysis? |
|
Definition
|
|
Term
| When does aerobic processing of the pyruvate molecules occur? |
|
Definition
| Aerobic processing of the pyruvate molecules occurs when they travel into the mitochondria and undergo the citric acid cycle followed by oxidative phosphorylation. |
|
|
Term
| What must pyruvate be converted into in order to enter the citric acid cycle? |
|
Definition
| Pyruvate must be converted into Acetyl CoA |
|
|
Term
| What happens to Acetyl CoA in the citric acid cycle? |
|
Definition
| It is oxidised to form a variety of products including reduced coenzymes such as NADH |
|
|
Term
| How is ATP generated during oxidative phophorylation and the electron transport chain? What can the ATP then be used for and what is the role of oxygen? |
|
Definition
| Reduced coenzymes such as NADH bring hydrogen ions to the mitochrondial membrane to form an electrochemical proton gradient. ATP is produced by ATP synthase coupled to the electromotive force from the movement of protons and then be coupled to energetically unfavourable reactions to allow them to continue. Oxygen is an important player in the aerobic oxidation as it the terminal electron acceptor. |
|
|
Term
| Why is pyruvate converted to lactate under anaerobic conditions? |
|
Definition
| This is because coenzymes such as NADH are at a limited supply within a cell and must thus constantly be recycled. For every glucose molecule converted into pyruvate two NADH molecules are generated but these must be oxidised back to NAD+ to allow the continuation of glycolysis. This occurs via the conversion of pyruvate to lactate in a redox reaction which oxidises NADH to NAD+ as it reduces pyruvate to lactate. This is thus important for the maintenance of glycolysis. |
|
|
Term
| What are the main (primary) producers of lactate? |
|
Definition
| Producers of lactate include red blood cells, white muscle, and astrocytes |
|
|
Term
| What are the main consumers of lactate? |
|
Definition
| Consumers of lactate include liver, heart, red muscle, and neurons |
|
|
Term
| Which cells can produce lactate and what are the three main factors that determine the amount of lactate produced? |
|
Definition
| Any cell undergoing glycolysis can produce lactate, however, what determines the amount of lactate produced is based around the type of metabolism the cell is doing, the efficiency of the mitochondria (efficient will produce less), and whether they have mitochondria at all. |
|
|
Term
| Why do red blood cells rely on glycolysis for their energy? |
|
Definition
| Red blood cells have no mitochondria at all and thus rely upon glycolysis for their energy despite carrying a high concentration of oxygen. Specifically this energy comes from anaerobic glycolysis. Pyruvate is thus converted to lactate as part of energy metabolism. |
|
|
Term
| How does lactate travel through the body? |
|
Definition
| Lactate travels through the body either dissolved in plasma or picked up by red blood cells. |
|
|
Term
| Why do red blood cells express MCT 1 (allows lactate in) as well as MCT 4 (allows lactate out)? |
|
Definition
| Red blood cells also express MCT 1 as well as the expected MCT 4 despite carrying out only anaerobic respiration as they have a role in transporting lactate around the body. |
|
|
Term
| Why does white muscle produce high concentrations of lactate during exercise? |
|
Definition
| White muscle is one of the broad categories of muscle which has a relatively smaller number of mitochondria and thus less capacity to carry out aerobic respiration. White muscle also has a small number of myoglobin which is able to help with storage of oxygen in the muscle cells. As a consequence, white muscle tends to convert most of our pyruvate into lactate. It is for this reason that white muscle is considered to be a fast muscle as it only gives short explosive bursts of power. |
|
|
Term
| What is meant by the symbiosis between red and white muscle and what is another example? |
|
Definition
| The lactate produced in the white muscle doesn't stay there and is instead generally released into the extracellular environment where it can travel to plasma as part of the circulating fluid and be picked up by the heart or liver (gluconeogenesis) for example. Of more immediate use, in the case of having white muscle next to red muscle, the lactate can move into the red muscle and used as an energy source. This is known as symbiosis between red and white muscle. Another example of symbiosis is astrocytes in the brain producing lactate for the neurons which use it to produce ATP. |
|
|
Term
| How is lactate used in consumer cells? |
|
Definition
| A relative abundance of mitochondria and high oxygenation allows the consumer cells to use the lactate as energy. It can contribute significantly to energy generation by being converted back into pyruvate then becoming Acetyl CoA and moving through the citric acid cycle. |
|
|
Term
| Why is lactate only partially oxidised and what does this mean? |
|
Definition
| Lactate and pyruvate both have three carbons and thus lactate represents a partial oxidation product. Because the lactate is only a partial oxidation it can be converted back into glucose in appropriate cells including the liver and kidneys. This is known as gluconeogenesis via the Cori cycle. |
|
|
Term
| Where and how is pyruvate converted back to glucose for example after exercise? |
|
Definition
| Once transferred through the blood to the liver, the lactate can be converted back to two pyruvate generating an NADH and then further to glucose converting NADH back to NAD+ and using 6 ATP (gluconeogenesis). Even though there is a cost of 6 ATP, this is repaid in aerobic respiration. Any lactate can be recycled back into glucose in the liver and the glucose can then be used by a variety of tissues. This is useful for starvation and strenuous exercise for example. |
|
|
Term
| Why does lactate require a transporter and does this differ in terms of lactic acid? |
|
Definition
| As lactate is a polar molecule it requires a transporter to move across the membrane. Lactic acid forms a small less polar proportion of lactate and may to an extent diffuse across the membrane. |
|
|
Term
| What are the family of transporters that are used to allow transportation of lactate across the membrane? |
|
Definition
| Lactate is transported by a family of monocarboxylate transporters (MCT) must be used. MCTs may also transfer other monocarboxylates such as pyruvate and monocarboxylate drugs. The MCTs we are going to consider are symporters and do co-transport with hydrogen ions. |
|
|
Term
| What is the difference between MCT 1 and MCT 4 transporters? |
|
Definition
| MCT1 is a high affinity (low KM) transporter suited to moving lactate into cells while MCT4 is a low affinity (high KM) transporter suited to moving lactate out of cells. |
|
|
Term
| What does a low KM signify and how is this evident in the case of MCT 1? |
|
Definition
| A low KM means high affinity allowing binding at low concentrations. In the case of MCT1 this is useful as the extracellular volume is relatively large compared to intracellular volume and thus lactate would be assumed to be of a relatively low concentration meaning high affinity binding is needed. |
|
|
Term
| Are MCT transporters direction specific? |
|
Definition
| No. Both transporters could move lactate in and out according to conditions. MCT 1 has high activity in low lactate concentrations moving them against the concentration gradient while MCT 4 is active in high concentrations of lactate generally moving molecules along the concentration gradient. |
|
|
Term
| Do all cells express the same MCT transporters? |
|
Definition
| Different cells will express different members of the MCT family depending on what they are trying to achieve. |
|
|
Term
| How do MCT 1 and MCT 4 relate to the symbiosis between glycolytic and oxidative muscle cells? |
|
Definition
| During exercise there is a high glycotic flux in white muscle cells which increases the production of lactate. MCT4 transports lactate out of glycolytic muscle cells (white muscle) and into oxidative muscle cells (red muscle) through MCT1. White muscle has a higher proportion of MCT4 and red muscle has a higher proportion of MCT1. |
|
|
Term
| What does lactase dehydrogenase catalyse and how does this vary in producers and consumers? |
|
Definition
| Lactate dehydrogenase catalyses the reaction from pyruvate to lactate and can catalyse it in either direction according to the cellular conditions. Consumers will catalyse lactate to pyruvate while producers catalyse in the forward direction from pyruvate to lactate. |
|
|
Term
| What type of enzyme is lactate dehydrogenase? |
|
Definition
|
|
Term
| How many possible isozymes are there for lactate dehydrogenase? |
|
Definition
|
|
Term
| What are the different subtypes of the subunits and which gene codes for which? |
|
Definition
| There are M (muscle) subunits and H (heart) subunits where the M subunits are coded for by LDH a and the H subunits are coded for by LDH b. |
|
|
Term
| How do the lactate dehydrogenase isozymes differ? |
|
Definition
| The lactate dehydrogenase tetramer can be made by any combination of the two subunits. Each combination has a different KM and thus affinity meaning they are more likely to catalyse particular directions of the reaction. All of the isozymes CAN catalyse either way even though they prefer one over the other. Different cells express different proportions of the isoenzymes according to the gene expression. |
|
|
Term
| Where is the M4 isozyme of LDH predominant and what can it tolerate? |
|
Definition
| Muscle and liver and can tolerate high lactate concentrations |
|
|
Term
| What reaction does the M4 LDH isozyme catalyse? |
|
Definition
| This isoenzyme can tolerate high concentrations of lactate and can either continue to convert pyruvate to lactate under anaerobic conditions for example in the muscle during anaerobic exercise or recycle lactate to pyruvate as in the liver. M4 is thus useful for converting pyruvate to lactate under high concentrations of lactate or recycling lactate when large concentrations enter the cell. |
|
|
Term
| Where are H4 LDH isozymes predominant? |
|
Definition
| In aerobic tissues such as the heart |
|
|
Term
| What reaction do H4 LDH isozymes catalyse and why? |
|
Definition
| H4 isoenzymes favour the conversion of lactate to pyruvate and are mainly found in aerobic tissues. It has a high affinity (low KM) for lactate and thus works even in lower concentrations grabbing the lactate and converting them as soon as they enter. This is important particularly in the heart as lactate can build up as an acid and hence lower the pH which reduces the efficiency of proteins involved in heart muscle contraction. This hence favours the use of lactate as an energy source. |
|
|
Term
|
Definition
| Tumours are fast growing and the middle of a tumour can be quite anaerobic and thus lactate produced by anaerobic cells feeds aerobic cells. The division is effectively uncontrollable allowing a mass to rapidly build up (the tumour) and grow so quickly that generated vasculature throughout the tumour is difficult hence the anaerobic centre. Cells close to blood supply can be considered aerobic while those further away can be considered anaerobic. |
|
|
Term
| What is the H4 LDH lysozyme also known as? How about M4? |
|
Definition
| LDH 1 for H4 and LDH 5 for M4 |
|
|
Term
| How do the affinity and KM change from LDH 1 to 5? |
|
Definition
| From 1 to 5 the affinty decreases and the KM increases |
|
|
Term
| What happens in the anaerobic tumour cells? |
|
Definition
| In an anaerobic cell energy is generated through glycolysis and pyruvate is then converted to lactate (cancer cells need a lot of energy). This lactate can leave the cell but often builds up to high concentrations and thus uses the isoenzyme of LDH 5 to catalyse the reactions. The predominant transporter is the low affinity MCT 4 which is best suited to moving lactate out of the cell. |
|
|
Term
| What happens in the aerobic tumour cells? |
|
Definition
| The aerobic cell can use lactate as an energy source. In order to do this lactate must be transported into the cell by the high affinity MCT 1 transporter which is predominantly expressed on aerobic cells. Lactate hence needs to be converted back to pyruvate which is best done by LDH 1 which has a high affinity and can thus utilise the lactate quickly and at low concentrations. |
|
|
Term
| How does the symbiosis between anaerobic and aerobic tumour cells occur? |
|
Definition
| The anaerobic cell effectively feeds the aerobic cell, however, as the aerobic cell uses the produced lactate as a fuel source it does not require as much glucose. The high concentrations of glucose in the blood, therefore, are mainly directed into the anaerobic cells as the aerobic cells can already fill their energy quota with the lactate and thus do not require much glucose. The glucose effectively diffuses into the deeper parts of the tumour at the anaerobic cells. This is referred to as symbiosis as both cells work together within the solid tumour. |
|
|
Term
| What is the role of lactate as a signalling molecule? |
|
Definition
| As well as entering the aerobic cells, lactate can also enter the endothelial cells of the blood cells through the MCT 1 transporter. In the endothelial cell the lactate signals the cell to change its gene expression to stimulate the production of more blood vessels. This is a pro-angiogenic effect as is promotes angiogenesis. |
|
|
Term
| How can we target cancer? |
|
Definition
| One way in which we may be able to target cancer is through targeting MCT 1 and MCT 4 through MCT1 and MCT 4 inhibitors to alter the movement of lactate into and out of the cells. |
|
|
Term
| What are the different types of regulation of metabolic pathways? |
|
Definition
| Types of regulation include gene expression changes (make more or less protein), metabolite supply (put in more or less substrate), feedback inhibition, feedforward activation, covalent modification, and allosteric regulation. |
|
|
Term
| What types of regulation involve enzymes? |
|
Definition
| Feedback inhibition, feedforward activation, covalent modification, and allosteric regulation are all due to the direct regulation of enzymes. |
|
|
Term
| What is glycolysis and what is generated? |
|
Definition
| Glycolysis is the pathway by which glucose is processed to make two pyruvate with a net gain of 2 ATP and 2 NADH along the way. |
|
|
Term
| What inhibits glycolysis? |
|
Definition
| In general glycolysis is inhibited by increased ATP, acetyl Co-A (fatty acids and ketone bodies), and citrate (pyruvate is converted to citrate suggesting that there is enough product). |
|
|
Term
| What is glycolysis regulated co-ordinately alongside? |
|
Definition
| It is co-ordinately regulated with glycogen metabolism, gluconeogenesis, and lipid synthesis (due to storage of glucose as glycogen and lipid). |
|
|
Term
| Why is feedback inhibition so important in the case of glycolysis? |
|
Definition
| Some cells such as red blood cells can only produce energy anaerobically due to a lack of mitochondria and thus rely on glucose for energy. For this reason it is important that glucose is only used when necessary to ensure there is always enough. This means feedback inhibition is particularly important. |
|
|
Term
| How was the pasteur effect set up and what happened? |
|
Definition
| The Pasteur Effect was set up in a conical flask containing anaerobic yeast with no oxygen (as yeast quickly consumes all of the oxygen) and a stopper at the top of the flask. The stopper was then removed to allow oxygen to enter. As air enters (and thus oxygen) the flask glucose consumption decreases. |
|
|
Term
| Why does glucose comsumption decrease in aerobic conditions compared to anaerobic conditions? |
|
Definition
| This is because when we metabolise glucose anaerobically we get a net gain of 2 ATP whereas when we metabolise it anaerobically we get a net gain of 32 ATP. If the energy requirements of the yeast don't change when switching to aerobic conditions and there is a greater net gain then less glucose needs to be consumed in order to meet the energy requirements of the yeast. |
|
|
Term
| Upon switching from aerobic conditions to anaerobic conditions what glycolytic intermediates increase/decrease and why? |
|
Definition
| There is an increase in glucose-6-phosphate and fructose-6-phosphate upon switching from anaerobic to aerobic but a decrease in fructose-1,6-bisphosphate and all the other intermediates downstream. In the glycolytic pathway, glucose forms G-6-P in an energy requiring step. F-6-P is then formed and in a subsequent energy requiring step so is F-1,6-P. Due to the build-up in products before F-1,6-P and a deficit in the products after, it is likely there is some form of feedback in the conversion of F-6-P to F-1,6-P. |
|
|
Term
| What happens when an aerobic yeast culture is set up and then placed under anaerobic conditions? |
|
Definition
| . Upon turning of the air there is a rapid increase in the amount of NADH produced. This is formed by the glycolysis pathway suggesting that glycolysis and thus glucose consumption is increased. In contrast the ATP concentration decreases. |
|
|
Term
| Why does the ATP concentration decrease when going from aerobic conditions to anaerobic? |
|
Definition
| This can be explained by the fact that a stimulation of the glycolytic pathway will also stimulate the energy investment phase hence contributing to the decrease in ATP. Concurrently with this the switch to the anaerobic mechanism means only two ATP are created by glucose in contrast to the 32 created aerobically. This would work to further decrease the amount of ATP particularly in relation to the aerobic pathway. Ie if you are using the same amount of glucose but generating less ATP then it would be expected that you would see a decrease in ATP levels. |
|
|
Term
| What happens when ATP levels start to drop? |
|
Definition
| As ATP decreases the amount of ADP increases. This is because ATP is converted to ADP by removing a phosphate group. The AMP levels are also increasing but in a slight lag compared to the ADP levels. |
|
|
Term
| Why do NADH levels begin to decrease again and ATP levels rise after the initial fall in ATP when moving from aerobic culture to anaerobic culture? |
|
Definition
| We know that we are consuming ATP in the energy investment phase but also making double the amount we lose in the energy payoff phase. It would thus make sense that after the initial increase in glucose consumption the ATP levels would again begin to increase. This happens at the same time that NADH is decreasing. This is because NADH needs to be recycled back to NAD+ through the lactate dehydrogenase reaction as there is a limited amount of coenzymes. The ATP level then decreases again after plateauing meaning the flux is again decreasing. |
|
|
Term
| What are the three main regulatory enzymes in the glycolytic pathway? |
|
Definition
| There are three key regulatory control points in glycolysis. These are regulated by the enzymes hexokinase, phosphofructokinase, and pyruvate kinase. |
|
|
Term
| What does phosphofructokinase regulate? |
|
Definition
| Phosphofructokinase is the enzyme that regulates the reaction between F-6-P and F-1,6-BP. |
|
|
Term
| What does hexokinase regulate? |
|
Definition
| Hexokinase regulates the first step of glycolysis which is an activation step following the equation Glucose and ATP go to form glucose-6-phosphate and ADP. |
|
|
Term
| What inhibits hexokinase and what type of regulation is this? |
|
Definition
| Increased levels of G-6-P signal high levels of ATP and glycolytic intermediates. This is a form of negative feedback (product inhibition) where sufficient G-6-P inhibits hexokinase. |
|
|
Term
|
Definition
| Glucokinase is another isoform which catalyses the same reaction as hexokinase but isn't subject to feedback inhibition. |
|
|
Term
| Why is glucokinase not inhibited when hexokinase is? |
|
Definition
| This is because it is performing a key - much different role - in the liver. It has a higher Km for glucose (thus a lower affinity only working at high concentrations of glucose) and a higher Vmax than hexokinase which is useful for shunting glucose to glycogen in the fed state. This means there is a lower affinity but a higher capacity. |
|
|
Term
| What does pyruvate kinase regulate? |
|
Definition
| Pyruvate Kinase catalyses the reaction of phosphoenolpyruvate and ADP to pyruvate and ATP. |
|
|
Term
| What is the arrangement of the pyruvate kinase enzyme? |
|
Definition
| Pyruvate kinase controls the last step of glycolysis and is a four subunit enzyme (tetramer) which can reversibly dissociate to a dimer when it is inactive. There are several isoenzymes (L, M, and A subunits). |
|
|
Term
| What are the inhibitors of pyruvate kinase? |
|
Definition
| It is inhibited by ATP, acetyl CoA, and alanine. |
|
|
Term
| What are the activators of pyruvate kinase? |
|
Definition
| It is activated by PEP (phosphoenolpyruvate) through co-operativity, fructose-1,6-bisphosphate, and AMP. |
|
|
Term
| What type of enzyme is pyruvate kinase? |
|
Definition
|
|
Term
| How do inhibitors and activators of pyruvate kinase alter the final form of the enzyme? |
|
Definition
| Pyruvate kinase is an allosteric enzyme and those compounds that activate the enzyme push it towards the tetramer form while those that inhibit it push it to the dimer state. |
|
|
Term
| Where are the M, L, and A isoenzymes of pyruvate kinase predominantly found? |
|
Definition
| M type is predominantly found in muscle, L type is primarily found in the liver, and A type is in all tissues in varying amount. |
|
|
Term
| Why does Acetyl CoA inhibit pyruvate kinase? |
|
Definition
| Because Acetyl CoA feeds into the citric acid cycle and thus sufficient acetyl CoA suggests sufficient amounts of product so less pyruvate needs to be generated. |
|
|
Term
| Why does alanine inhibit pyruvate kinase? |
|
Definition
| Alanine inhibits pyruvate kinase as pyruvate is the keto acid for alanine so if there is enough alanine there is enough of the product pyruvate. |
|
|
Term
| How does PEP (phosphoenolpyruvate) allosterically activate pyruvate kinase? |
|
Definition
| When PEP binds to one subunit of the tetramer it promotes the binding of more PEP to the other subunits thus increasing affinity. |
|
|
Term
| How does F-1,6-BP activate pyruvate kinase? |
|
Definition
| F-1,6-BP acts as a feed forward activator to prepare pyruvate kinase for incoming substrate. |
|
|
Term
| How does AMP activate pyruvate kinase? |
|
Definition
| AMP arises in the cell under a low energy state and thus stimulates pyruvate kinase to increase the production of ATP through the conversion of phosphoenolpyruvate to pyruvate. |
|
|
Term
| What is the liver isoenzyme also regulated by and how does this occur? |
|
Definition
| The liver isoenzyme of pyruvate kinase is also regulated by glucagon. Glucagon induces the cAMP dependent phosphorylation of pyruvate kinase. Phosphorylation inhibits pyruvate kinase and down-regulates liver glycolysis during fasting. |
|
|
Term
|
Definition
| Glucagon is the hormone that signals the fasted state in the body. |
|
|
Term
| Why does glucagon inhibit liver pyruvate kinase? |
|
Definition
| In the fasting state the liver ultimately wants to make glucose available to the rest of the body and thus we don't want the liver to be doing glycolysis but rather doing gluconeogenesis or releasing glucose from glycogen. |
|
|
Term
| What is the key regulatory enzyme for glycolysis and what determines flux through glycolysis? |
|
Definition
| Phosphofructokinase is the key regulatory enzyme of glycolysis and determines the overall flux of glycolysis. |
|
|
Term
| What is the structure of phosphofructokinase? |
|
Definition
| Phosphofructokinase is also a tetramer (like pyruvate kinase) with several isoenzymes and can switch between the tetrameric form and dimeric form where the tetramer is more active. |
|
|
Term
| What inhibits phosphofructokinase? |
|
Definition
|
|
Term
| How does ATP inhibit phosphofructokinase and what amount of ATP is enough to inhibit phosphofructokinase? |
|
Definition
| Physiological (steady state) concentrations of ATP inhibit phosphofructokinase as the concentration is too high. This occurs because ATP binds to phosphofructokinase both at the active site where there is a high affinity (meaning it prefers lower concentrations) and at an allosteric site where there is a low affinity and so ATP will only bind at high concentrations. AT low concentrations of ATP the enzyme is in the R state and is thus less in a better conformational state to bind ATP while at high concentrations of ATP the enzyme is in the T conformational state having a higher Km and thus a lower affinity for F-6-P at the active site. |
|
|
Term
| What state is phosphofructokinase in during high and low ATP concentrations? |
|
Definition
| In high concentrations of ATP it is in the T state and at low ATP it is in the R state where the T state is more active. |
|
|
Term
| Does phosphofructokinase behave as a Michaelis-Menton enzyme and what happens when/if it doesn't? |
|
Definition
| In low concentrations of ATP phosphofructokinase behaves as a Michaelis-Menton enzyme in the R state (normal curve) compared to a sigmoidal curve in the T state. |
|
|
Term
| Why and how does citrate inhibit phosphofructokinase? |
|
Definition
| Citrate can inhibit phosphofructokinase as it essentially means there are lots of Citric Acid Cycle intermediates. Citrate hence enhances allosteric phosphofructokinase ATP binding and thus inhibits phosphofructokinase as there is no need to metabolise more glucose and thus waste it. |
|
|
Term
| How do activators of phosphofructokinase work and what are they? |
|
Definition
| Activators of phosphofructokinase relieve the ATP inhibition of phosphofructokinase. This is activated by AMP and F-2,6-P. These are allosteric effectors that stabilise the R state of phosphofructokinase. |
|
|
Term
| Why do increased AMP concentrations activate phosphofructokinase? |
|
Definition
| Increased AMP concentrations signal low energy state. The concentrations of ATP and ADP only vary over a few orders of magnitude while typically AMP levels are very low so an alteration is magnified and thus is a very sensitive indicator. Under low levels of ATP two ADP molecules can be used to make ATP and a AMP. This only occurs under low energy states and hence AMP only appears when there is very low energy available. |
|
|
Term
| Why does F-2,6_BP activate phosphofructokinase? |
|
Definition
| F-2,6-BP is also an activator and is an alternative product of F-6-P. This activates phosphofructokinase by increasing the affinity of the active site for F-6-P. If phosphofructokinase-1 is inhibited the F-2,6-P can be formed instead to stimulate phosphofructokinase once again hence allowing glycolytic flux to continue as building up of the intermediate products inhibits hexokinase hence stopping glucose moving through glycolysis. |
|
|
Term
| What is the nitrogen from amino acids used for? (7) |
|
Definition
| Making neurotransmitters, phospholipids, coenzymes, purines, pyrimidines, porphyrins, and thyroxine. |
|
|
Term
| What can we use the carbon skeleton of an amino acid for? |
|
Definition
| Can be stored as fat via Acetyl CoA, through gluconeogenesis can be stored as glucose or glycogen, or oxidised via glycolysis and the citric acid cycle to generate energy. |
|
|
Term
| What happens to nitrogen that is not required? |
|
Definition
|
|
Term
| Can we store nitrogen and if not what happens to it? |
|
Definition
| There is no dedicate store for nitrogen or nitrogen compounds in humans (unlike carbon). Nitrogen that is not required is excreted. |
|
|
Term
| What is nitrogen balance and what is it dependent on? |
|
Definition
| Nitrogen balance is the the relative amount of nitrogen coming into the body compared to the relative amount excreted. This is dependent on an dietary nitrogen intake and physiological state. |
|
|
Term
| What does it mean by being in nitrogen balance and who would be in nitrogen balance? |
|
Definition
| The amount of nitrogen excreted is equivalent to the nitrogen intake. This is the status quo. |
|
|
Term
| How can nitrogen be excreted? |
|
Definition
| Faeces, skin loss, urine, perspiration, and hair loss. |
|
|
Term
| What is positive nitrogen balance? |
|
Definition
| When the amount of nitrogen intake exceeds the nitrogen excretion. |
|
|
Term
| Who would we expect to be in positive nitrogen balance? |
|
Definition
| Growing children and adolescents, pregnancy, and body building and is thus related to growth. |
|
|
Term
| What is negative nitrogen balance? |
|
Definition
| When the excretion of nitrogen is greater than the intake. |
|
|
Term
| When would we expect someone to be in negative nitrogen balance? |
|
Definition
| During illness and starvation or if the nitrogen intake is inadequate in terms of which amino acids are being consumed. |
|
|
Term
| How can someone excrete more nitrogen than their intake? |
|
Definition
| We are forced to excrete nitrogen every day due to compulsory losses. |
|
|
Term
| What happens in the body if there is insufficient intake of dietary amino acids? |
|
Definition
| Catabolism (break down) of mainly muscle proteins to release essential amino acids. |
|
|
Term
| What are essential amino acids? |
|
Definition
| Amino acids we cannot make in the body. |
|
|
Term
| What do we do with excess amino acids? |
|
Definition
| Excess amino acids can be utilised for energy by removing the alpha amino groups. |
|
|
Term
| Why does catabolism of muscle protein occur in the case of insufficient dietary intake and what does this mean for the body? |
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Definition
| The essential amino acids are required are required for essential bodily processes and thus if there isn't great enough intake they must be sourced from elsewhere. This occurs via catabolism and doesn't just release essential amino acids but also non-essential amino acids. This means we have more non-essential amino acids than needed in the amino acid pool and these are subsequently broken down by the body into carbon skeletons by removing the amino group depending on the physiological state of the body. |
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Term
| When else (aside from insufficient nitrogen intake) would protein catabolism occur? |
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Definition
| When there is insufficient ennergy intake. Catabolism would be for the purpose of carbon skeleton generation for energy by removing the nitrogen to form a fuel source. |
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Term
| What happens in the case of excess amino acid intake? |
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Definition
| The excess amino acids can be stored as carbon skeletons and used for energy once the amino acid groups have been removed. |
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Term
| What are transaminations? |
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Definition
| Transaminations allow for the shuttling of amino acids between keto acids. |
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Term
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Definition
| Deaminations allow for the release of an amino acid to the cytosol or donation to another metabolic intermediate that is not an amino acid precursor or keto acid. |
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Term
| What are the main compounds that allow for the transport of nitrogen and how? |
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Definition
| Glutamate and glutamine can be deaminated to release an amino group or synthesised from alpha ketoglutarate and glutamine respectively) which mops up nitrogen and allows for its transport. |
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Term
| How can new amino acids be created and what determines which amino acid is created? How would you create glutamine? |
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Definition
| Transamination can create a new amino acid by adding amino groups to various keto acids. The formed amino acid depends on the used keto acid for example alpha ketoglutarate is the keto acid for the amino acid glutamate. |
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Term
| What catalyses the transamination and how is the enzyme named? |
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Definition
| Aminotransferase enzymes are used and these are named according to the amino acid that is donating the amino group for example glutamate aminotransferase if glutamate is donating the amino group. |
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Term
| What enzyme catalyses glutamate deamination and what is the reaction? Can this occur in both directions if so why? |
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Definition
| The enzyme is glutamate dehydrogenase and the reaction is glutamate + NAD(P)+ <=> alpha ketoglutarate + NAD(P)H. This is a redox reaction and can hence occur in reverse. |
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Term
| At physiological pH what form will released amino groups be in? |
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Definition
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Term
| How is glutamine deaminated? |
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Definition
| Glutamine has two amino groups: one in the side chain and one alpha amino group. The side chain amino group is removed first using the enzyme glutaminase which forms glutamate and an ammonium ion. The glutamate dehydrogenase reaction then removes the amino acid from the resulting glutamate. |
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Term
| What reaction is used to deaminate glutamine to glutamate and can it be reversed? |
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Definition
| Glutamine + water => glutamate + ammonium ion. Catalysed by glutaminase. This cannot be reversed. |
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Term
| What reaction is used to deaminate glutamate to alpha ketoglutarate and can it be reversed? |
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Definition
| Glutamate + NAD(P)+ + water <=> alpha ketoglutarate + NAD(P)H + ammonium ion. Catalysed by glutamate dehydrogenase. Can be reversed. |
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Term
| How is glutamine synthesised from glutamate? |
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Definition
| Glutamate + ammonium ion + ATP => glutamine + P + ADP. Catalysed by glutamine synthetase |
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Term
| What is the primary transporter for nitrogen on its way to the liver? |
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Definition
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Term
| Why can't the ammonium ions travel to the liver dissolved in the blood stream? |
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Definition
| Ammonium ions in the blood stream can be toxic hence why it is generally picked up by glutamate to form glutamine. |
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Term
| What is synthesised instead of glutamine in muscle cells to carry amino groups to the liver and what does this mean? |
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Definition
| Glutamate undergoes a transamination reaction with pyruvate to form alanine and alpha ketoglutarate. This is catalysed by glutamate aminotransferase. This reaction is then reversed in the liver using alanine aminotransferase to release a pyruvate as well as generate the glutamate as the pyruvate can be combined with another pyruvate to form glucose for use in energy formation. |
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Term
| What happens to the released amino group in the liver? |
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Definition
| It is incorporated into urea. |
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Term
| Where is urea synthesised and what happens after synthesis? |
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Definition
| Urea is synthesised in the liver then transported to the kidney for excretion via the blood stream. |
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Term
| How mean nitrogen atoms are excreted per molecule of urea? |
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Definition
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Term
| How does nitrogen enter the urea cycle? |
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Definition
| As carbamoyl phosphate and aspartate (amino acid) |
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Term
| How is carbamoyl phosphate formed? |
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Definition
| From an amino group (deamination of glutamate and glutamine) and carbon dioxide in the reaction catalysed by carbamoyl phosphate synthetase in an energy requiring reaction using 2ATP |
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