Extremes of Metabolism Flashcards
what are the two types of. muscle fibre
type 1 slow switch
type 2 fast switch
How do fast twitch generate energy from metabolism
- the muscles metabolism is mostly glycolysis
- ATP comes from energy that is generated in glycolysis
- they are NOT rich in mitochondria
what are the divisions of fast twitch muscle
they can be further divided into type 2A and B
what is the difference between type 2A and B fast twitch muscles
Type A
- aerobic as it contains myoglobin therefore it has a store of oxygen
- it has intermediate capillary density
- it has high oxidative capacity
- high glycolytic capacity
- and intermediate glycogen content
type B
- anaerobic
- low capillary density
- low oxidative capacity
- high glycolytic capacity
- high glycogen content
How do slow twitch generate energy from metabolism
- they generate tension more slowly
- get ATP from oxidative metabolism int he mitochondria
- they are rich in mitochondria
what is the difference between slow twitch and fast twitch
Fast Twitch
- the muscles metabolism is mostly glycolysis
- ATP comes from energy that is generated in glycolysis
- they are NOT rich in mitochondria
Slow twitch
- they generate tension more slowly
- get ATP from oxidative metabolism int he mitochondria
- they are rich in mitochondria
the portion of each muscle group…
can vary - this depends on the type of exercise and training that you do, for example marathon runners would have more slow twitch than fast twitch whereas sprinters would have more fast twitch
how much can metabolic demand in skeletal muscle for ATP increase during exercise
100 times
how can muscle ATP regerneated
- phosphocreatine - this can be used as a temporary buffer for ATP in order to regenerate the energy supply to the muscle
- muscle glycogen
- blood glucose
- blood fatty acids
what is the order of energy storage from phosphocreatine, glycogen and triglyceride
- the most is triglyceride (17500Kj)
- then glycogen (8000Kj)
- then phosphocreatine (15 kJ) which has very little stored
what does AMP do
- it acts as an important metabolic signal
- it increases glucose uptake and utilisation and this turns on glycolysis in the short term and fatty acid oxidation in the long term
- it causes the body to switch between these sources and therefore make ATP
what has sufficiency capacity to provide ATP during sprinting
muscle glycogen
how does muscle glycogen breakdown during sprinting
- breakdown is linked to calcium
- calcium causes contraction of the muscle
- when calcium binds to calmodulin it activates phosphorylase kinase
- this activates glycogen phosphorylase
this conversation the breakdown of glycogen into glucose -1-phosphate - acts as an allosteric effector of glycolysis
what does pyruvate dehydrogenase control
- it controls the entry into the TCA
what controls pyruvate dehydrogenase
- it is controlled by phosphorylation via pyruvate dehydrogenase kinase
- pyruvate dehydrogenase kinase is activated by low levels of NADH and ATP and this inactivates pyruvate dehydrogenase by phosphorylating it
- calcium activates pyruvate dehydrogenase phosphatase which activates pyruvate dehydrogenase and this activates it by dephopshorylating it
what enzymes in the TCA are controlled by calcium
- Calcium and ADP activate alpha-ketoglutarate dehydrogenase and isocitrate dehydrogenase
what is an allosteric activation of glycogen phosphorylase
- AMP acts as an allosteric activator of glycogen phosphorylase
- this only happens when it is not phosphorylated
- it can make the inactive form active as the AMP overrides the hormonal control therefore it promotes glycogen breakdown providing more fuel
when is glycogen phosphorylase activated
when it is phosphorylated
what enzymes are allosterically activated by AMP
- glycogen phosphorylase - start of glyconeolysis
- phosphofructokinase -1 - start of glycolysis
what membrane channel does AMP try to increase
- AMP what’s to increase the transport of glucose through the cells and it does this by increasing the number of GLUT4 membrane channels therefore allowing glucose to enter
describe the structure of AMP kinase (AMPK)
- it is a heterotrimer
- made up of 3 subunits
- 2 regulatory and one catalytic subunit
what does the AMPK (AMP kinase) do
- This increases the number of GLUT4 glucose transporters on the muscle membrane
- This happens independent of insulin
how is AMPK controlled
- it senses energy status via specific domains on the gamma subunit
- can be controlled by phosphorylation on Thr172 of the alpha subunit - this is not dependent on AMP
when AMP is high …
it activates AMPK
what inhibits phosphofructokinase 1
- it is allosterically inhibited by high levels of ATP
what activates phosphofructokinase 1
- ADP and AMP - this relieves high levels of ATP
- in the heart - phosphofructokinase 1 is used, this produces fructose-2,6- bisphopshate which activates PFK1
what controls phosphofructokinase 2
- controlle dyb phosphorylation via AMP kinase
what happens during prolonged exercise
- there is a shift from glucose to fatty acid metabolism
what causes the shift from glucose to fatty acid metabolism in prolonged exercise
= mediated by AMPK
- AMPK phosphorylates cytoplasmic acetyl-CoA carboxylase this inactivates it
- prevents the build up of this in the cytoplasm
- this activates the carnitine shuttle and transports fatty acids into the mitochondria for breakdown
- by in activating ACC it means that you no longer get malonyl CoA this blocks the cartinine shuttle therefore you are still able to transport fat into the mitochondria and therefore you are able to do fat metabolism
why do you feel muscle fatigue
- running out of glycogen
- depletion of phosphocreatine
- excessive rates of conversion of glycogen and glucose to lactic acid - this decreases pH and inhibits glycolysis and oxidative phosphorylation
- insufficient (ageing), inflexible (obesity or ineffeicny mitochondria - the density of mitochondria increase with exercise therefore you may not have the ability to switch to oxidative metbaolism in order to be able to meet needs
how do you break down alcohol
- Ethanol is converted to acetyaldehyde this happens by alcohol dehydrogenase (produces NADH), catalase (produces water) microsomal ethanol oxidising system[produces P450] (produces NADP and water)
- Acetaldehyde and oxidised NAD is turned into acetate and NADH this reaction is catalysed by acetylaldehyde dehydrogenase
- ATP and acetate and CoA goes to AMP and PPi and acetyl-CoA
- Acetaldehyde and oxidised NAD is turned into acetate and NADH this reaction is catalysed by acetylaldehyde dehydrogenase
is acetylaldehyde toxic
- Acetylaldheyde is toxic
what does disulfiram do
anatabuse is the trade name, this blocks the enzyme acetylaldheyde dehydrogenase, this means that if you take this drug you end up with more acetylaldehyde -feel unwell more quickly therefore you stop drinking
what are the genetic differences in acetaldehyde dehydrogenase efficiency
- Acetylaldehyde dehydorngease – better efficiency in Asian people therefore they feel the negative effects of alcohol more than people who do not have this genetic
what are the biochemical effects of alcohol
- High levels of NADH
- High levels of acetylCoA
what does high levels of NADH cause
- TCA cycle inhibited – malate dehydrogenase
- Lactate dehydrogenase
- Pyruvate dehydrogenase – glycolysis is inhibited
- Shuts down gluconeogenesis
what do high levels of acetyl CoA cause
- Driven into fatty acid synthesis
- Ketone body production
why does the immune system need energy
- Reactive oxygen species – this is bad for bacteria therefore they can be used as a method of attack
- Anabolism of immune mediators – making atnibodies
- Phagocytosis
what type of energy demand does the immune system have
- it has a variable energy demand
what are the ways in which the immune cells can make energy
- To make the reactive oxygen species, a lot of NADPH is used, this can be made in two ways this happens in the pentose phosphate
- Converts malate to pyruvate can also produce NADPH
- Top up malate by using the amino acid glutamine
how does the immune system make energy
- Oxygen add electron to form superoxide can then turn into hydrogen peroxide and then hypochlorite
- Requires energy – get it from NADPH from pentose phosphate or metabolism of malate
- Because malate withdraws stuff from the TCA cycle it has to be topped up by glutamate and glutamine in order for it to keep on functioning
what do cancer cells produce even when oxygen is present
lactate
what is it called when cancer cells produce lactate even when oxygen is present
- This is called the Warburg effect
describe metabolism of cancer cells
- Cancer cells produce lactate even when oxygen is present
- This is called the Warburg effect
- This means that cancer cells often make use of glycolysis even when oxygen is present this is because they have a very high demand of for energy
- Replication requires a large amount of energy to be used
- High demand for amino acids like glutamine and glutamate feeding into the TCA cycle as fuel
- Energy and metabolites for growth so TCA cycle needs toping up
- Heterogentiy within a tumour
