Explain ligands binding to receptor
-Cell communication using chemical or electrical signals/ligands that activate complex signalling pathways
-Must be able to regard, communicale and amplify a signal.
-Many molecules can not pass the cell membrane, therefore require receptors.
-Epinephrine entering the liver binds to Beta-adrenergic receptor causing conformational change, activating G protein.
-G proteins contains alpha,beta and gamma subunits.
G protein > GDP exchanges GTP > Alpha detaches > binds the Adenylyl Cyclase > ATP > cAMP > Protein Kinase A > Phosphorylase K > glycogen > glucose.
Amplification occurs as cAMP activates many Protein Kinase A
Regulation: hypoglycaemia, GTP to GDP on alpha subunit, turns offstream events off.
Signal, transduction and amplification definitions
Signal is the message in the form of a metabolite called a ligand. The ligand binds to a cell receptor and docks. The ligand changes the shape of a receptor. An example could be Epinephrine.
Transduction is when the signal is changed from an extraceullar signal to an intracellular signal. This is appropriate for a response from the cell.
Amplification occurs when the ligand binding does not create a big enough response to the signal. Therefore the cell can become efficient and use molecules in low concentrations and produce a rapid response. An example is when a G protein activates many adenylyl cylases, then each cAMP will activate several protein kinases. The end result is a rapid production of glucose from a low concentration of epinephrine.
Describe the MAPK pathway
The Map Kinase pathway is a cascade responsible for growth factors.
The signalling molecule: Epidermal Growth Factor, to grow, to divide. If there is a problem with the MAPK signalling, it can cause malignancies.
The receptor: Epidermal Growth Factor Receptor, a receptor tyrosine receptor that dimerizes and phosphorylates. GRB2 and SOS bind to the phosphate on the RTK, Ras is able to now bind.
Core kinase molecules: Ras must be activated, so GDP is converted into GTP, activated by SOS. The activated Ras then activates RAF. Raf activates MEK. MEK activated the ERK
Secondary messengers: MAPK enters into the nucleus and activates transcription factors of the AP-1 family that produce proteins for cell growth and division.
At each stage, a few molecules of one kinase will phosphorylate a large number of the next, producing amplification.
Another molecule, GAP binds to the Ras-Raf complex, GTP is then hydrolysed back to GDP. This turns off the pathway. Mutated Ras proteins still create a kinase, however they cannot hydrolyse GTP- back to GDP, therefore the pathway remains on and cell proliferation is uncontrolled.
Briefly outline the process of gluconeogenesis.
The creation of glucose from non-sugar processor molecules such as pyruvate, lactate, glycerol and amino acids. This process occurs in liver and kidney cells as they are responsible for regulating glucose levels in the blood. The liver and kidney cells create the glucose via gluconeogenesis and release the glucose into the blood so it can be used by skeletal, brain and cardiac muscles.
Glycolysis transforms glucose into pyruvate and gluconeogenesis transforms pyruvate back into glucose, however this step does not simply follow the reversible step of glycolysis.
Glycolysis is very exergonic that releases a lot of energy so it would cost to convert this back, therefore gluconeogenesis bypasses steps 1,3,10 of glycolysis as these are irreversible and exergonic steps and would require the most energy for transformation.
Pyruvate comes from the breakdown of glucose therefore it can be reversed back into glucose.
Lactic acid when cells run out of oxygen as glycolysis is faster than oxidative phosphorylation, resulting in lactate fermentation.Lactic acid dissociates into lactate. The lactate travels through plasma to the liver and is transformed into pyruvate by lactate dehydrogenase.
Glycerol molecules are components of triglycerides that exist in adipose tissue. Adipose cells break down triglycerides into fatty acids and glycerol molecules. The glycerol can be used to form glucose by travelling in plasma to hepatocytes in the liver. Glycerol is transferred into glycerol phosphate and oxidised into DHAP.
Amino acids can be broken down from skeletal muscles in starvation to form glucose molecules. Certain amino acids are broken down into pyruvate and some make DHAP molecules and enter gluconeogenesis.
We can only store a specific amount of glucose and glycogen in bodily fluids. Athletes tend to have a higher demand for glucose and the reserves of sugars cannot be met if sugar stores are depleted. Gluconeogenesis therefore allows the body to create glucose which is turned into ATP required by our cells in absence of stored or digested glucose/glycogen.
Describe the structure of the TCA cycle.
i. Pyruvate (3C) is converted into Acetyl CoA (2C) by Pyruvate Dehydrogenase Complex and also produces 1 NADH and CO2.
ii. Oxaloacetate (4C) binds to Acetyl CoA (2C), creating Citrate (6C). Enzme:Citrate Synthase
iii. Citrate (6C) is becomes Cis-aconatate (6C) and then Isocitrate (6C). EnzymeAconitase
iv. Isocitrate (6C) losing a CO2 and producing 1NADH, creating alpha-ketoglutamate (5C). EnzymeIsocitrate Dehydrogenase
v. Alpha-ketoglutamate (5C) loses a CO2 and produces 1NADH, creating Succinyl-CoA (4C). Enzyme a-ketoglutamate complex
vi. Succinyl CoA (4C) is converted to Succinate and produces a GTP. enzyme Succinyl-CoA Sythetase
vii. Succinate becomes Fumarate and a FADH2 is produced.enzyme Succinate Dehydrogenase
viii. Fumarate becomes Malate. enzyme Fumarase
ix. Malate becomes Oxaloacetate and completes the cycle, making 1NADH. Malate Dehydrogenase
How the metabolism of certain compounds leads to o
Alcohols are organic compounds used in a variety of toiletries, pharmaceuticals and fuels. However, alcohol is best known in the form of alcoholic beverages called ethanol. Alcohols contain a hydroxyl group and this is responsible for the properties and reactions.
Ethanol’s metabolism follows a biochemical pathway.
i. Ethanol is converted into Acetaldehyde by alcohol dehydrogenase, producing an NADH molecule.
ii. Acetaldehyde is converted into Acetate by acetaldehyde dehydrogenase, producing a NADH molecule.
iii. Ethanol can only be metabolised at a certain rate, regardless of the amount drunk. Alcohol dehydrogenase works quicker than Acetaldehyde Dehydrogenase, consequence in excess Acetaldehyde, the hangover.
iv. The biochemical pathway produced 2 NADH molecules that signal changes in metabolism. >This includes increased glycolysis, which can cause severe hypoglycaemia
>Increased Pyruvate, causing Lactic Acidosis and a low blood pH
>Most importantly increases fat synthesis where the hepatocytes take in excess lipids and produce more triglycerides but less oxidation. This causes triglycerides to accumulate in the liver and produce lipid venules. Decreases fat breakdown, induces a fatty change of the liver (steatosis).
v. Fatty Live Disease: steatosis, fatty accumulation in the liver. Continuation of bad foods, ethanol and drugs causes inflammation (steatohepatitis).
vi. Fat accumulation, liver cell necrosis, inflammation and fibrosis.
vii. End stage Cirrhosis: shrunk, nodules, irreversible.
Describe the mechanism involving a metabolic disea
Occur when abnormal chemical pathways in the body are altering the normal metabolic pathway. Metabolic pathways are co-ordinated to meet the needs of the bodies for exercise or nutrition.
Diabetes, is when there is a complication of glucose entering cells and providing them energy; instead the glucose accumulates in the blood (hyperglycaemia). When food containing carbohydrates and sugars are broken down into glucose, they must enter cells with the help of insulin hormones. The pancreas produces insulin and triggers blood glucose to enter cells.
The pancreas contains areas called the Islets of Langerhans and they contain beta cells. The beta cells create insulin in response to ingested glucose.
Glucose builds up to abnormal high levels making the person hyperglycaemic as the glucose cannot enter the cells and the cells are starved of energy. The liver recognizes cell starvation and begins gluconeogenesis, further raising glucose levels. The excess glucose is excreted through the kidneys as urine. Starved cells begin to metabolise protein, leading to loss of intracellular potassium, phosphorus and amino acids. This in turn causes excessive fluid loss from cell and a disrupted electrolyte balance. Water loss exceeds glucose loss and is excreted excessively through to kidneys (polyuria). The liver still continues to produce glucose and converts amino acids into urea, leading to further electrolyte imbalance.
Illustrate the importance that allostery plays in
Aside from enzymes having active binding sites, many also contain an allosteric site and these are named allosteric enzymes. Allosteric enzymes influence enzyme activity by changing conformation of the protein by the binding of a substrate from a site other than the active binding site. Small molecules or ions called effector molecules can bind to allosteric sites to activate or deactivate enzyme activity. This is known as allosteric regulation.
Negative Feedback Inhibition: If the effector molecule inactivates the enzyme, the effectors are called inhibitors. Glycolysis required many enzymes, importantly hexokinase, which converts glucose to glucose-6-phosphate. When too much glucose-6-phosphate has built up, glucose-6-phosphate binds to an allosteric site and this inhibits the hexokinase enzyme.
Explain the terms Km, Kcat and Keq
Enzymes are catalysts that speed up biochemical reactions.
Measuring enzyme rates under different conditions is the study of enzyme kinetics .
The enzyme substrate relationship =Michaelis-Menten equation.
The Michaelis-Menten equation describes the “ideal” enzyme kinetics.
Km is known as the Michaelis constant. Km can only be depicted on a graph plotting the concentration of the substrate and the velocity. The Km shows that the substrate has reached ½ Vmax, meaning that the enzyme is half-saturated with substrates. The lower the Km, the better affinity the substrate and enzyme have. Competitive inhibitors increase the Km and not the Vmax as competitive inhibitors bind to active sites, blocking substrates from binding; however do not cause a reaction. Non-competitive inhibitors reduce the Vmax and not the Km
Kcat is the key concept of turnover rate. It is defined as the maximum number of substrate molecules that can be converted into product per active site of enzyme per second. Kcat is independent of the enzyme. The Kcat or turnover number of an enzyme can be derived from Vmax
i. Keq defines a reactions equilibrium constant measuring the extent which reactants are converted to products by the reaction. Equilibrium does not necessarily mean that the reactants and products are in equal amounts, it means that the reaction has reached a point where the concentration of the reactant and the product are unchanging with time as because they are switching between each other and back again at the same rate. this value can only be changed by temperature.