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92 Cards in this Set
- Front
- Back
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What is glycolisis?
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It is lysing up glucose to produce ATP and NADPH. It occurs in all tissues for energy and it can be aerobic or anaerobic.
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What is the function of ATP and NADPH?
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Mainly they are molecules with high energy bonds that are used as fuel.
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What is pyruvate?
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1. It is the end product of glycolysis.
2. It gets converted into Acteyl CoA in aerobic glycolysis and to lactic acid in anaerobic |
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What is the importance of regulation in biochemical reactions? What are the main regulating enzymes in glycolysis?
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It is the key to biochemistry.
1. Hexokinase 2. PFK-1 3. Pyruvate kinase |
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What is Phosphofructokinase stimulated inhibited by?
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PFK-1 is the most important regulatory enzyme in glycolysis and it is stimulated/inhibited by F26 Bisphosphate
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What happens to the gylcolytic rate during fasting or eating?
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During the well fed state glycolysis slows down because there is a lot of glucose around and energy need not be wasted to break it down.
During the fasting state energy is needed more quickly and the glucose needs to be broken down more quickly. |
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What is the basic function of a phosphatase and a kinase?
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A phosphate takes a phosphate off a protein.
A kinase adds a phosphate to a protein. |
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What do glucagon and insulin do?
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Glucagon promoted gluconeogenesis and the breakdown of fat stores to raise blood sugar.
Insulin promotes the storage of glucose into gycogen by the breakdown of glucose into high energy molecules and lowering blood sugar. |
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What does cAMP do in cells?
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It is an important second messenger that when activated sends signals to regulate reactions.
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How do RBCs produce their energy?
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They produce it through anaerobic respiration because they are too small for mitochondria. They are contributers to lactic acidosis seen in active SKM. A deficiency in PFK1 can cause hemolytic anemia.
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How are pyruvate and ethanol related?
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In microrgansims alcohol metabolism is the only one that occurs and pyruvate is eventually turned into ethanol.
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What can a pyruvate kinase deficiency cause?
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1. A defect in this cuauses the second most common form of hemolytic anemia
2. This is becuase the Pyruvate is not made and RBCs cannot produce the energy needed to keep up their biconcave structure and autolyse. |
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What are the 10 major molecules in the glycolytic pathway?
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1. Glucose
2. G6P(Glucose6phosphate) 3. F6P(Fructose6phosphate) 4. F1,6P (Fructose1,6phosphate) 5.G3P (Glyceraldehyde3phosphate) 5a. DHA (Dihydroxyacetone) 6.1,3BPG (1,3 Bisphosphoglycerate) 7.3PPG (3Phosphoglycerate) 8. 2PPG(2Phosphoglycerate) 9. PEP(Phosphoenolpyruvate) 10. Pyruvate |
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Why do we have the Tricarboxyllic cycle(TCA) and what is the main substrate for it?
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Produces way more energy than glycolysis alone. The main reason we have glycolysis is to produce Acetyl CoA as a substrate for the TCA.
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What are the three stages of catabolism?
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Stage 1 is the breakdown of big complex molecules into managable building blocks.
Stage 2 is the breakdown of the building blocks into Acetyl CoA Stage 3 is oxidative phosphorylate on Acteyl CoA into ATP and CO2 through the TCA. |
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What does the liver do for the rest of the body?
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It stores the glucose into glycogen.
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Where do we have aerobic glycolysis?
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Lots in cells with abundant O2 and mitochondria. All cells really.
Tissue dependent glycolysis occurs in; RBC, Eyes, Kidney medulla, testis, leukocytes, white muscle fibers. They have just a little mitochondria and this is how they get their ATP. |
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What is the overall reaction of glycolysis in an aerobic pathway?
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C6H12O6 + 6O2 + 6H2O =
6CO2 + 6H2O + 32ATP |
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What do the side reactions in glycolyis do?
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They help conserve energy. The cells produce ATP by the controlled burning of glucose.
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Stage 1 of glycolysis, the priming of glucose?
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1. Hexokinase(mostly) sometimes glucokinase will phosphorylate D-Glucose to G6P. This traps the glucose and is an irreversible step.(ATP)
2. Interconversion of G6P and F6P by phosphofructokinase. Easily reversible 3. F6P to F1,6BP by PFK-1. Irreversible.(ATP) 4. This step uses a total of 2 ATP as an energy investment |
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Stage 2 is the splitting of the phosphorylated intermediate and how does it work?
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1. F1,6BP is split into DHA and GAP by FBP aldolase(reversible)
2. GAP and DHA are interconverted by triphosphate isomerase. 3. Now 1 molecule of glucose is split into 2 GAPs. |
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Stage 3 is oxidoreduction and ATP synthesis and how does this work?
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1. GAP is oxidized to 1,3BPG by GAP dehydrogenase. Oxidation here reduces NAD+ to NADH and requires on inorganic phosphate(Pi)
2.NADH must be oxidized back for glycolysis to continue. Happens later in the ETC or pyruvate to lactic acid. 3. 1,3BPG to 3PPG is accomplished by PGK creating and ATP by taking one off 13BPG. 4. A side reaction here causes 1,3BPG to be mutated into 2,3BPG and using phosphatase to go to 3PPG. 5. 3PPG mutated to 2PPG by PPG mutase. 6. 2PPG to PEP by enolase. This makes PEP with a high energy Phosphate that has a high -G. 7. PEP quickly goes to Pyruvate by pyruvate kinase creating another ATP. |
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What is the significance of the 2,3BPG intermediate?
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It is needed to give red blood cells this reaction. 2,3BPG is an allosteric inhibitor of O2 binding and lets O2 release more easily into the blood.
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What is catabolism?
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The set of metabolic pathways that break down molecules into smaller units and release energy.
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Why is there more than one step in catabolism?
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This is because it can utilize the maximum amount of energy release per breakdown. Also in tissues catabolism raises the energy and the mechanisms need to prevent a meltdown in the tissues. Many catabolic reacctions require O2 consumption and electron acceptors are needed to transform that energy by oxidative phosphorylation.
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What is the role of Acetyl CoA in catabolism?
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Acetyl CoA serves as an electron acceptor for the various catabolites. It transfers the electrons into a high energy yield cycle the TCA.
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What is the difference between catabolism and anabolism?
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1. Catabolism takes the high energy yielding products and breaks them down. This produces chemical energy and other poor energy products; CO2, H2O, NH3 and heat.
2. Anabolism converts the building blocks, using chemical energy, into complex molecules used fro structure, information and sometimes energy. |
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What happens with glucose in an MI?
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Levels are raised because the blood is not moving glucose and transferring it for breakdown.
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What happens to burn victims and their glucose levels?
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They have low glucose levels. This is because the are dehydrate and have a high energy usage to keep the body alive. The body also goes into a fasting state and trys to break down storage molecules for more energy.
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What are 3 types of cell signalling?
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1. Synaptic signaling
2. Endocrine signaling 3. Direct contact signaling |
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How does synaptic signaling work?
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It is used between nerve cells, or nerve and muscle cells. The body uses these to transmit electrical impulses followed by vesicular release in the syapse.
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What is endocrine signaling?
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It is the slowest form of signaling when the body releases molecules into the blood. They are then carried to their target site and used for regulation of body function.
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What is direct contact signaling?
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This is the quickest form of communication in the body. The cells use gap junctions and usually is a form of local control.
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What is a transmembrane protein?
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They are proteins that span and entire biological domain. The can be alpha helices or beta barrels. You must use non-polar solvent or detergents to detach these.
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What is a protein domain?
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It is a protein sequence and structure that can evolve, function, and exist independently of the rest of the protein chain.
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What are the subunits of a G protein?
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A G protein uses GTP for energy. The three subunits combined span the membrane, alpha, beta, and gamma.
G-alpha binds GTP and interacts with adenyl cyclase. G-betagamma is necessary for alpha subunit interaction with its receptors, and affects targets later on. |
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How do G proteins work?
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1. The alpha subunit must be bound to the 7 transmembrane domain receptors.
2. The GTP displaces GDP and causes alpha to bind to the protein. 3. The Gaplha protein positively stimulates adenyl cyclase. 4. The Gbetagamma affects downstream effectors |
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What does Adenyl cyclase do?
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Adenyl cyclase once activated will stimulate cAMP synthesis using ATP. The cAMP then activates PKA.
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Protein Kinase A
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This phosphorylates proteins and can activate or deactivate them. It definately charges them and traps them in the cell.
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cAMP and PKA does what together?
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cAMP causes the dissociation of the catalytic and regulatory subunits of PKA, and this activates the enzyme.
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What does a phosphatase do?
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It uses H2O to dephosphorylate a protein.
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What happens in aerobic versus anaerobic glycolysis?
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The products of both reactions is Pyruvate, 2ATP and NADH. In aerobic glycolysis pyruvate is released to go into the TCA.
In anaerobic glycolysis Pyruvate is taken a step further to lactate using NADH. This means that there was ATP production but no net NADH production. |
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What does the GLUT-1 transporter do?
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Transports glucose in the BBBarrier, Muscle, Heart, Glia, Erythrocytes
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What does the GLUT-2 transporter do?
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Transports glucose through the plasma membrane in the Liver, pancrease, intestine and kidney.
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What does the GLUT-3 transporter do?
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Transports glucose through the plasma membrane in the brain, kidney, placenta.
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What does the GLUT-4 transporter do?
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Transports glucose through the plasma membrane into the muscle, adipose tissue and heart.
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What does the GLUT-5 transporter do?
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Transports glucose through teh sarcolemma into Muscle and spermatazoa.
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What is a cotransporter?
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It works by binding 2 molecules or ions at a time and using the gradient of one to force the other against its gradient.
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What is facilitated diffusion?
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It works by having transport proteins that allow the spontaneous transport of specific molecules. The GLUT transporters use this form of transport.
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What is the total energy yield of glycolysis?
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2 pyruvate +2 NADH + 2 ATP + 2H+2H2O
The yield of anaerobic is the same until it turns pyruvate into lactate using its 2NADH. |
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Hexokinase characteristics
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Used in the fasting state. It has a low Km which means it has a high affinity. It has to ability to mop up the small amounts of glucose. It is the main one used in tissues. It has a low Vmax meaning that it will not be able to proceed very quickly and only makes enough product for the cell to use.
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Glucokinase characteristics
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It is used in the well fed state and it has a high Km so a low affinity for glucose. It has a high Vmax so the glucose can be broken down quickly and then used for energy as well as storage.
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What is the net energy yield of aerobic glycolysis?
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It is
2 pyruvate 2 ATP 2NADH |
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How do you activate glucose?
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Begin by adding a phosphate using one of the kinases. This action traps glucose in the cell by charging it.
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What is the comitted step in glycolysis?
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Turning F6P into
F1,3BP using PFK-1 and ATP is the comitted step in glycolysis. |
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How does the cell regulate glucokinase?
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It is not regulated by direct action of the pathway. Glucokinase is inactivated by glucokinase regulatory protein(GKRP).
F6P will bind glucose back to GKRP and put it to sleep. Free glucose cause the release of GK from GKRP. GK is a glucosensor that will increase insulin lecels |
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How does one regulate the other hexokinases?
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Inhibit it by its direct product G6P. Stimulate it with glucose.
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How do you isomerize G6P to F6P?
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Catalyze this reaction by Phosphoglucose Isomerase. the PGI reaction is reversible.
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What is meant by aldose/ketose isomers of G6P and F6P?
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G6P is and aldose with oxygen on its end and aldehydes have lots of energy.
F6P is a ketose and they are more stable. |
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What regulates the coversion of F6P to F1,3BP, using PFK-1?
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High levels of high energy molecules such as citrate and ATP will inhibit this reaction.
PFK-1 is activated even during high levels of ATP by F26BP. |
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What happens during the conversion of F6P to F2,6BP using PFK-2?
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It is a side reaction of F6P when glycolysis kicks into overdrive.
PFK-2 is a bifunctional complex that can turn F6P into F2,6BP and back. PFK-2 is active without a phosphate and inactivated with one. F2,6BP is a molecule that signals lots of glucose during a well fed state. When this happens glycolysis speeds up. Reductions of F2,6BP will decrease the rate of glycolysis. |
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What would high levels of glucagon do to glycolysis?
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Glucagon activates a adenyl cyclase that activates cAMP.
cAMP in turn will activate PKA. PKA will cause the phosporylation of PFK-2 This causes a reduction in glycolysis. |
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What happens when PFK-2 is inactive?
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This means that there is little need for glycolysis and gluconeogenesis is probably happening. Or it could mean that only hexokinase is giving the necessary energy to the cell.
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What happens when FBP-2 is in an active state?
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It means that not much F2,6BP is present. Means that you are not in a well fed state. It also means that you probably have the need for gluconeogenisis.
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What happens when PFK-2 is being dephosphorylated?
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It is activating the enzyme. That means that F2,6BP is being made and speeding up the process of glycolysis. You are in a well fed state and insulin/glucose levels are high.
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What happens when F2,6BP levels are reduced?
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Glucose levels are not very high in the cell and glycolysis levels are at a normal rate. Hexokinase is probably the main enzyme turning Glucose into G6P. PFK-2 levels are not very high.
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What happens during the cleavage of F1,6BP and DHA isomerization?
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It is an unregulated reversible reaction. Aldolase-A cleave F1,6BP into glyceraldehyde 3 phosphate and dihydroxyacetone.
Most of the DHA must be isomerized into G3P to continue the glycolysis. |
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What are the main actions of insulin on glucose?
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It pulls glucose out of the blood and puts it into the liver. The liver stores it as fat or uses it for energy.
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Is the PFK-1 activity stimulated by ATP?
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No PFK-1 is not stimulated by ATP, it is inhibited by ATP because that is an energy rich signal. It does however use ATP as a substrate to add a Pi to G6P to make F1,6BP.
F2,6BP can also stimulate PFK-1 activity. |
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Is the PFK-1 activity inhibited by AMP?
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No the PFK-1 activity is stimulated by AMP because it signals that the cell needs more energy and therefore more glycolysis.
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Is PFK-1 activity stimulated by F2,6BP?
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Yes because even at high levels of ATP, F2,6BP is the most potent stimulator of PFK-1. It is one of the sensors that lets us know we are in a well fed state and need to break down this sugar and store it or use it.
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Which molecules affect PFK-1 activity?
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High levels of energy rich ATP and citrate will inhibit activity.
High levels of AMP and F26BP will stimulate activity |
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What reaction does PFK-1 catalyze?
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PFK-1 catalyzes the conversion of G6P to F1,6BP.
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What is the role of phosphorylation in these reaction?
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Phosphorylation of F6P to F26BP is the comitted steo in glyocolysis.
Alternative phosphorylation to F2,6BP can cause an increase in catalytic activity of glycolysis. |
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What happens during high levels of Glucagon?
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It stimulates Adenyl Cyclase to produce cAMP
to activate PKA to phosphorylate PFK-2 that inactivates it that activates FBP-2 that works during gluconeogenisis |
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What happens during the oxidation of G3P?
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G3P is converted to 1,3BP using glyceraldehyde-3-phosphate dehydrogenase.
This step requires Pi and NAD+ to oxidize and add a phosphate. The NAD+ from this step later gets regenerated in the ETC or pyruvate/lactate conversion The addition of this high energy phosphate drives the next ATP synthesis. |
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What is the relationship between are
arsenic poisoning and energy deprivation? |
Arsenic complexes with G3P and skips the ATP generating steps and goes directly to 3-phosphoglycerate. This ATP is necessary for providing cellular energy.
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What is the cellular shunt reaction?
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It is the mutation of 1,3BPG to 2,3BPG. 2,3BPG is then phospatiscized to 3-Phosphogylcerate. This skips an ATP producing step , and is a reaction commonly found in RBCs.
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How does the synthesis of 3-phosphoglycerate work?
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1,3BPG is converted to 3-Phosphoglycerate using phosphogycerate kinase. This is a reversible reaction that generates ATP.
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What is substrate level phosphorylation?
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It is energy produced for reactions outside of the ETC.
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What are mutase enzymes?
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They are enzymes that in general switch the position of molecules on the substrate.
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What happens during the dehydration of 2 phosphoglycerate?
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Enolase takes away a water and converts 2-phosphogylcerate to phosphoenol pyruvate. This is a reversible reaction that redistributes the energy.
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What happens during the formation of pyruvate?
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PEP is take to pyruvate by pyruvate kinase. This is the second reaction that produces ATP. This is also the third irreversible glycolytic reaction.
Feed forward regulatoin by F1,6BP stimulates this reaction. |
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How does one inhibit or stimulate PK?
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Stimulate it by feed forward of F1,6BP.
Glucagon will inhibit this reaction by stimulation of PKA and cAMP that will phosphorylate this enzyme and inactivate it. |
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How does pyruvate kinase deficiency relate to hemolytic anemia?
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Without PK the cell will not produce enough high energy compound to maintain the RBC shape and function. This is the second most common form of enzyme deficiency related anemia.
The first most common form is caused by a G6P dehydrogenase deficiency. |
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What are 3 signs of a PK deficiency?
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The enzyme shows an abnormal response to F1,6BP, normally an activator.
The enzyme may have an abnormal Km or Vmax for its substrates or coenzymes. The enzyme activity or stability may be altered or the amount of enzyme is decreased. |
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How is the formation of lactate accomplished?
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Pyruvate is converted to lactate in the final step of anaerobic glycolysis. The lactate is formed by lactate dehydrogenase. The majority is done in poorly vascularized areas or places that lack mitochondria.
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How is lactic acid formed in the muscle?
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It results from the energy demand superceding the oxygen consumption.
There is not enough oxygen to oxidize the NADH and break down the G3P. This elevates the NADH/NAD+ ratio This results in more lactic acid formation and results in elevated pH and cramps. |
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What is lactic acidosis?
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During a stoppage of circulation the O2 transportation failure results in an increase in anaerobic respiration for energy.
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What does the morbidity mortality?
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Oxygen debt from lactic acidosis is related to this. One can detect the debt by measuring lactic acid build up.
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How does arsenic poisoning relate to lipoic acid?
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Lipoic acid is a necessary component of the production of pyruvate dehydrogenase. Without lipoic acid no Acetly CoA would be produced and not enough energy would be formed. Lipoic acid is also vitamin B3.
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What are the regulatory effects of insulin and glucoagon?
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Insulin increases GK,PFK,PK and glucagon decreases the actions of all these.
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