Met: PBL 4 (Exercise and Metabolism) INCOMPLETE Flashcards
What is EPO?
A gene that codes for erythropoietin, a secreted glycosylated cytokine in the plasma which regulates red blood cell production by promoting erythroid differentiation and initiating haemoglobin synthesis
What is PFK-1?
Phosphofructokinase 1 - it catalyses the ‘committed’ step of glycolysis; the conversion of fructose-6-phosphate and ATP to fructose 1,6-bisphosphate and ADP
What metabolic pathways would a sprinter use most?
ATP Phosphocreatine pathway, anaerobic glycolysis
What metabolic pathways would a marathon runner use most?
Aerobic glycolysis and fatty acid respiration
Describe the percentage use of different fuels during a 4 hour exercise period
Blood fatty acids = 62%
Muscle glycogen = 8%
Blood glucose = 30%
What is the immediate energy source for exercise?
ATP
Describe the ATP-phosphocreatine pathway
Phosphocreatine –> creatine and inorganic phosphate (creatine kinase enzyme) –> ADP combines with released inorganic phosphate –> ATP (ATP synthase enzyme) –> ATP goes to myosin fibres in myofibrils to allow release of myosin heads from the actin filament
What does creatine kinase do?
Breaks down phosphocreatine into an inorganic phosphate and creatine
Write an equation to represent anaerobic glycolysis
Glucose + 2Pi + 2ADP –> 2lactate + 2ATP + 2H2O
State four metabolic fuels used by exercising skeletal muscle to provide ATP
Any of: phosphocreatine, glycogen (muscle/liver), glucose (blood), amino acids, free fatty acids, triacylglycerol/triglyceride, ketones
Why does anaerobic exercising muscle export lactate to the liver instead of pyruvate in the cori cycle?
Anaerobic glycolysis in exercising muscle requires NADH to be reoxidised to NAD+ for glucose breakdown to continue –> in the absence of oxygen the ETC cannot reoxidise the NADH and therefore, pyruvate is reduced to lactate by LDH in order to regenerate NAD+. Therefore, lactate is exported instead of pyruvate, otherwise anaerobic glycolysis would be unable to continue to supply energy to the muscles
Why do top endurance athletes increase their consumption of pasta shortly before a race?
.Glucose from digested pasta helps to build-up stores of liver glycogen
Why do top endurance athletes increase their consumption of B-group vitamins shortly before a race?
.B-group vitamins generate coenzymes essential for the complete oxidative metabolism of glucose (coenzyme for the phosphate dehydrogenase complex which converts pyruvate to acetyl-CoA which allows entry into the krebs cycle)
Outline the mechanism whereby hypoxia brings about appropriate adaptations to enhance energy metabolism in skeletal muscle
Hypoxia stabilises the HIF-1a subunit of the transcription factor HIF, which would ordinarily be degraded under normoxic conditions. This stabilisation of the 1a subnit allows HIF-1 to bind to hypoxia-response elements in the promoter regions on metabolic genes –> the effect of this is to up-regulate glycolysis and suppress mitochondrial activity (stimulate mitochondrial autophagy)
What is VEGF?
Vascular endothelial growth factor (VEGF) is a signal protein produced by cells that stimulates vasculogenesis and angiogenesis. It is part of the system that restores the oxygen supply to tissues when blood circulation is inadequate such as in hypoxic conditions.
Outline the stages in anaerobic respiration
Glycolysis –> 2 x pyruvate –> 2 x lactate (via LDH enzyme which oxidises 2 NADH to 2 NAD+) –> Reformed NAD+ then goes on to supply further glycolysis to produce 2 ATP per glucose molecule
Name the stages of aerobic respiration
Glycolysis, formation of acetyl CoA, Krebs (TCA) cycle, electron transport chain (oxidative phosphorylation)
Describe the process of glycolysis
Glucose –> glucose-6-phosphate –> fructose-6-phosphate –> fructose-1,6-bisphosphate –> GAP (3C compound so stages hereafter occur twice per molecule
Describe how pyruvate is converted to acetyl CoA
Via the PDC complex in the mitochondrial matrix which requires several cofactors and is a multi-step enzyme (including TPP derived from vitamin B1)
Describe the TCA cycle
Citrate –> isocitrate –> alpha ketoglutarate –> succinyl CoA–> succinate –> fumarate –> L-malate –> oxaloacetate
Acetyl CoA formed from pyruvate via the PDC complex gives up acetate, which then combines with oxaloacetate within the mitochondrial matrix to form citrate. This process primarily works to reduce NAD+ (2NADH per cycle) and FAD (1 FADH2 per cycle) to feed the ETC, 1 ATP produced per cycle also (substrate level phosphorylation)
Describe the electron transport chain
Reduced coenzymes are oxidised and feed electrons into the ETC–> ETC uses electron transfer down the electrode gradient to pump protons from the mitochondrial matrix into the inner membrane space –> ATP is produced by using the energy stored in this proton gradient to drive the ATP synthase protein (chemiosmosis)
What is the cori cycle?
Cycle which allows anaerobic metabolism to occur; the lactate produced is converted to glucose in the liver
Where does the hydrolysis of triacylglycerol take place?
In the cytosol of adipose cells –> glycerol and free fatty acids
Where does beta oxidation occur?
In the mitochondrial matrix; acyl CoA molecules are transported into the mitochondria via the carnitine shuttle
How are fatty acids activated?
By being bound to CoA in the liver or muscle cytosol –> acyl CoA
Outline the steps involved in fatty acid respiration
Triacylglycerol –> glycerol + free fatty acids (lipase enzyme).
Glycerol –> phosphorylated and oxidised –> DHAP –> isomerisation –> GAP –> enter gluconeogenesis or glycolysis (pyruvate or glucose produced)
Free fatty acids –> bind to albumin –> muscle or liver cells –> oxidation –> bind to CoA –> acyl CoA (formed in cell cytosol) –>beta oxidation in mitochondria matrix (transported in by carnitine shuttle) –> acyl CoA degraded by sequence of reactions resulting in shortening of the FA by 2Cs per sequence –> acetyl CoA –> TCA cycle
What is the role of glycogen phosphorylase enzyme?
Enzyme that uses phosphate to split alpha-1,4-glycosidic bonds in the glycogen molecule (with the aid of cofactor PLP) to produce glucose-1-phosphate and [glucose]n-1 molecule
What is the role of amylo-alpha-1,6-glucosidase enzyme?
Enzyme which removed the alpha-1,6-glycosidic bonds in the branches of glycogen to release free glucose
What is the role of phosphoglucomutase?
Catalyses the converted of glucose-1-phosphate to glucose -6-phosphate which can be used in glycolysis or converted to glucose in the liver
What is the role of glucose-6-phosphatase?
Converts glucose-6-phosphate to glucose in the liver in order to modulate (increase) blood glucose levels
Outline the process of glycogenolysis
Glycogen has it’s glycosidic bonds broken so through the use of glycogen phosphorylase to release free glucose monomers in the form of glucose-1-phosphate which can then be converted to glucose-6-phosphate by phosphoglucomutase –> glucose-6-phosphate will either enter glycolysis or be converted to glucose in the liver to module blood glucose levels
What type of muscle fibre do endurance athletes have the most of?
Type 1 fibres
What type of muscle fibre do sprint athletes have the most of?
Type 2 fibres
What type of muscle fibres are present in a normal individual?
45% type 2, 55% type 1
What are type I muscle fibres?
Slow myosin heavy chain fibres, involved in slow speed and small force movements –> present in large quantities in endurance athletes
What are type II muscle fibres?
Fast myosin heavy chain fibres, involved in fast speed and medium-large force exertion –> present in large quantities in sprinters
What determines the fuel used for exercise?
Muscle fibre type, amount of fuel stored (e.g. glycogen in muscle or liver), transport of fuel to the muscle, availability of oxygen, exercise intensity, exercise duration
What is HIF-1?
Protein transcription factor that is activated in hypoxic conditions
What ordinarily happens to HIF-1 under normoxic conditions?
The HIF-1a subunit of the transcription factor degenerates
What is the role of GLUT1?
Transporter in red blood cells and most cell membranes which is insulin-dependent and provides basal glucose transport to cells
What is the evolutionary advantage of HIF-1 activation in hypoxic conditions?
It reduces the likelihood of ischaemia due to reduced oxidative stress as mitochondrial respiration is down-regulated so mitochondria aren’t creating free radicals which could cause ischaemia
Describe the role of HIF-1 in hypoxic conditions
Enhances glucose metabolism by inducing expression of GLUT1 (insulin-dependent and found on most cell membranes), several glycolytic genes, induces expression of non-metabolic targets such as EPO and VEGF in order to increase oxygen carrying capacity in response to chronic hypoxia
Outline what happens when HIF-1 is activated
Active HIF-1 binds to hypoxia-response elements (HREs)
How do PFK-1 levels change with increasing altitude and why?
Increased levels of PFK-1 due to a greater demand for anaerobic respiration, which relies solely on glycolysis, of which PFK-1 is the rate-limiting factor
What molecules allosterically inhibit PFK-1?
High ATP levels (ATP:AMP ratio) - ATP increase lowers the affinity of PFK-1 for fructose-6-phosphate.
What molecules allosterically activate PFK-1?
High AMP:ATP ratio and fructose-2,6-bisphosphate (formed from use of PFK-2 on fructose-6-phosphate)
What is the most potent allosteric activator of PFK-1?
Fructose-2,6-bisphosphate
How is fructose-2,6-bisphosphate formed in glycolysis?
Through the use of PFK-2; fructose-6-phosphate –> fructose-2,6-bisphosphate
Why does lactic acid build up during endurance exercise?
Because body begins converting pyruvate to lactic acid at faster rate that it can burn lactate for energy –> builds up and increases muscle acidity
What is the evolutionary advantage of lactic acid build-up?
Increased muscle acidity –> interferes with metabolising glucose for energy –> slows overall energy production –> prevents overworking muscles to the point of causing damage or injury
Name two ways in which lactate/lactic acid can be used?
Oxidation back to pyruvate by well-oxygenate cells –> entry into the TCA cycle thereafter OR conversion to glucose via gluconeogenesis in the liver (Cori cycle) and released back into circulation to modulate blood glucose levels
Describe the role of alpha-1,4alpha-1,4-glucan transferase
Enzyme that moves the terminal 3 glucose residues from an outer branch of glycogen and move them to another in order to form a linear structure which can be broken down into glucose monomers more easily
