Coordinating Metabolism - Fuel Storage Flashcards
why do we need fuel molecules?
because we can’t store ATP or transfer it to other tissues, it must be made in the cell requiring it at the time by oxidising fuels
- biosynthesis, mechanical work, other energy requiring life processes
Pathway:
Fuels and ADP + Pi undergo catabolism to make CO2, H2O and ATP
Then ATP and something do anabolism to make ADP + Pi again and something else
describe out fuel stores in the fed state
- after a meal there is an excess of fuel, so the excess is stored
- glucose is stored as glycogen in liver and muscle
- fatty acids are stored as triacylglycerol droplets in adipose
- there is NO protein store
- the stored energy can be accessed when needed
- required to maintain glucose levels
- necessary for us to survive prolonged fasting or starvation
what are our most important/larges energy stores?
Fat is by far the biggest energy store (in adipose)
- animals show high capacity for fat storage (bears in hibernation, longish eel travelling long distance without feeding to spawn)
Another important one is the glycogen stores (in muscle and liver)
describe fat storage (form)
- triacylglycerols (TAGs)
- stored as fat droplets in adipose tissue
- excess TAGs and glucose from diet can be converted to stored fat
- unlimited fat stores
- in adipocytes (fat cells) the cytoplasm and all the organelles have basically be pushed to the side so the cell is mostly made up of lipid droplets
describe TAG synthesis in adipocytes (which is driven by insulin)
Glucose provides glycerol-phosphate backbone and provides acetyl-CoA for de novo lipogenesis (DNL)
1. insulin promotes glucose uptake via GLUT4 (previous lecture)
2. insulin stimulates glycolysis via hexokinase
- half way along the pathway it produces a three carbon molecule. DHAP can be converted into glycerol phosphate which provides the backbone for TAG synthesis/
3. Insulin also promotes the uptake of FFAs from lipoprotein particles by stimulating LPL. LPL hydrolyse the TAG core of the chylomicrons to release FFAs which come into the cell. These FFAs can then undergo a series of enzymatic events where they are added onto the backbone produced in 2, to create TAGs - this process is called lipogenesis.
4. insulin also stimulates DNL (pathway)
- if you get significant amounts of Acetyl-CoA getting made (which you will with an influx of glucose), it can be used to re-make free fatty acids. Happens via an enzyme complex caked fatty acid synthase (this is de novo synthesis of FFAs).
fat storage summary
Circulating glucose is taken up by adipose (via GLUT4 - stimulated by insulin) and liver (via GLUT2 - NOT stimulated by insulin!)
- dietary fat is packaged into chylomicrons
- in adipocytes glucose is metabolised to glycerol-3-phosphate and used as the backbone for TAG synthesis
- Insulin activates lipoprotein lipase (LPL) which hydrolyses TAGs to increase FFA into tissues where they are resynthesises into TAGs
- Glucose undergoes glycolysis in the liver generating excess acetyl-CoA that can be synthesised into FFAs via the FFA synthase complex, then into TAGs and packaged into VLDL particles
describe some key features of converting glucose to fatty acids
- excess glucose carbon can be converted to fatty acids via acetyl-CoA
- occurs mainly in the liver but also in adipose
- energy-requiring process
- FFAs exported as TAGs and VLDL
- FFAs delivered to adipose via LPL activity and stored as TAGs
- stimulated by insulin
describe the structural and chemical features of glycogen
- branched polysaccharide (large chains of glucose units joined together by glycosidic bonds)
- alpha,1-4 and alpha,1-6 glycosidic bonds (which gives it its branched structure)
- stored in liver and muscle
- granules in cytoplasm
- acts as a store of glucose
describe the process of glycogen synthesis
This process is stimulated by insulin, which activates a few enzymes (hexokinase, GLUT4 and glycogen synthase)
- glucose comes into cell via capillaries and GLUT4 transporters on cell membrane once insulin binds to its RTK receptor
- hexokinase is stimulated by insulin which traps glucose in cell
- glucose undergoes glycolysis pathway (hexokinase is the first step)
- in one of the last steps of glycolysis, UDP is added to the glucose molecule, making UDP-glucose.
- insulin then activates glycogen synthase, which diverts this molecule from glycolysis and takes the UDP-glucose and adds it onto the polymer of glycogen
describe the glycogen synthase reaction
- UDP-Glucose gets rid of UDP which forms an oxonium ion intermediate
- the negative charge on the glycogen residues and the positive charge on the oxonium ion intermediate form a glycosidic bond (by the loss of an H+)
- this forms glycogen (n+1 residues)
describe how glycogen synthase is activated
- stimulation of the insulin signalling pathway (due to insulin binding to RTK) activates PKB (and AKT) which inactivates glycogen synthase kinase (GSK3) - by adding a phosphate to it
- inactivation of GSK3 prevents glycogen synthase from being phosphorylated which keeps it active
- insulin also activate posphatase (PP1) which dephosphorylates glycogen synthase, which also keeps it active
describe some key features of glycogen synthesis
- occurs mainly in liver and muscle immediately after a meal
- requires energy inputs (ATP and UTP)
- activated high-energy precursor, UDP-glucose
- glycogen synthase and branching enzyme
- stimulated by insulin
- only so much space for glycogen (100g in liver and 280g in muscle), so excess glucose is converted to acetyl-CoA and then into fatty acids by the FFA synthase complex in the liver
describe glycogen gransules in liver cell
Granules ~0.1 micro meters
Mitochondria ~10 micro meters
Dark dots = glycogen
liver glycogen is important for maintaining blood glucose levels
describe what glycogen in muscle cells looks like before and after excersise
Muscle glycogen can only be used within muscle, as muscle cells are missing glucose-6 phosphatase
- before: prominent glycogen can be seen. its between and around the cells
- after: glycogen not as prominent (has been used) ?? cells are closer together/more defined in the image bc less glycpgen ??
