This summary includes all the information that you need for the course Food And Metabolism. The summary is 108 pages long, because it contains a lot of information, but also a lot of describing pictures which means that you can go fast through it. By reading and understanding this summary you don't...
→ The energy that comes free by ATP → ADP can be used for (pink square)
→ This ATP needs to be regenerated and this will be done by oxidation of fuel molecules
(discussed today) or photosynthesis
➢ Sources of ATP during exercise
→ You use ATP to exercise → During sprinting this ATP will last only a few seconds in your
muscle → You only have like 100 grams of ATP in your body so you have to refill this ATP
storage → That happens in muscles by breaking down the creatine phosphate
→ So using the creatine phosphate you can restore some of the energy in very short time
especially in the muscle
, ➢ Standard free energies of hydrolysis of compounds in biological systems
→ This can be done because hydrolysis of the phosphate group of the creatine phosphate
will render more energy than going from ATP to ADP → So you can use your breakdown of
creatine phosphate to resynthesize your ATP and in this way you can sprint a few seconds
longer
→ However after that your creatine phosphate is depleted and you need other sources of
energy which can be of the anaerobic metabolisms or the aerobic metabolism
➢ Stages of catabolism
→ Today we focus on the glucose metabolism
→ The breakdown of glucose happens in 3 steps:
1. STAGE 1: The breakdown of the bigger molecules in to smaller molecules where
there is little ATP production
2. STAGE 2: You convert your glucose in to Acetyl CoA and you get a little bit of ATP
production
3. STAGE 3: Oxidative phosphorylation → Bulk of ATP production
➢ Glycolysis
→ The glycolysis is the main pathway by which glucose is converted in to acetyl CoA which
can go in to the citric acid cycle
➢ ATP production by glycolysis
→ You get ATP production by glycolysis which can result in to muscle fiber contractions
and you end up with pyruvate
,→ If you have the pyruvate you can either turn this in to lactate if there’s low oxygen or the
pyruvate can go into the mitochondria in to the citric acid cycle and you can generate ATP
from that
➢ First steps of glycolysis cost ATP
→ The first steps of the glycolysis will cost ATP → So in the cell first glucose is transported in
to the cell which is bidirectional → First glucose needs to be trapped in the cell and be
activated before it can go further in to metabolism
→ So the first step is done by hexokinase → This step costs energy and the phosphate group
of ATP will be transferred to glucose-6-P which can then go further in the glycolysis where it
will turn in to fructose-6-P → Another ATP it will cost using the phosphofructokinase
→ Then you have fructose-1,6-biphosphate → This will cost energy
→ After that the fructose-1,6-BP will be split in to 2 C3 molecules and this will enter the 2nd
phase of the glycolysis where you will generate ATP
➢ Stage 2 of glycolysis generates ATP
→ At the end you get the phosphoenolpyruvate which can be converted by pyruvate kinase
in to pyruvate
→ So in the end you have the net generation of 2 ATP and 2 NADH molecules for 1 glucose
molecule
➢ NAD+ is regenerated through metabolism of pyruvate
→ There is a limit of NAD+ in a cell → If you don’t regenerate your NAD+ glycolysis will stop
→ So you have to regenerate NAD+ to get the glycoses going → Can be done in 3 methods:
, 1. If we have no oxygen (in our type 2B muscle fibers / fast switch fibers) then pyruvate
is turned in to lactate at the expense of NADH which is regenerating NAD+ → This
lactate can move from the muscle to the liver where it can be regenerated in to
glucose
→ This way the muscle cell can at least regenerate the NAD+
→ Also microbes and red blood cells can do this
2. Other cells don’t use this method, but do have enough oxygen to further oxidate the
Acetyl CoA in the citric acid cycle and in this way you can also regenerate your NAD+
3. Yeast and microbes have 3rd method → Going from pyruvate to ethanol and then
they regenerate NAD+ and can keep the glycolysis going
→ So this step is really important because NAD+ is limiting
➢ Regulation of glycolysis during high [ATP]
→ So the glycolysis is highly regulated at rest when you have a low consumption of ATP
→ You have high ATP levels and these high levels will block the pyruvate kinase and inhibit
the phosphofructokinase and lead in to an increase in glucose-6-P which has a negative
feedback on its own enzyme hexokinase
→ So by having a high level of ATP in a cell (rest) you have a low flux through the glycolysis
because you don’t need that much ATP
→ However if you go to sprint then suddenly the amount of ATP needed will increase by 100
folds → So suddenly there is tremendous amount of ATP needed
➢ Regulation of glycolysis during low [ATP]
→ This switch can be really fast
→ So if your cell is depleted form energy then this AMP will signal and will stimulate the
phosphofructokinase to stimulate reactions from fructose-6-P to fructose-1,6-BP → So the
process from glucose to glucose-6-P is not inhibited anymore and you get more fructose-
1,6-BP which has a positive feedforward stimulation on your pyruvate kinase and this drives
more flux through your glycolysis
→ This is when you need more ATP in your muscle suddenly (when you start to run)
, ➢ Rapidly growing cells use glycolysis
→ PET scan: tumor can be visualized due to high glucose intake
→ Also rapidly growing cells use a lot of glucose to grow
➢ Hypoxia alters gene expression and increase flux through glycolysis
- High lactate production → Inhibition of local immune system
- Anaerobic exercise training → Enhance muscle strength
→ The tumor cells depend on the glycolysis for their energy → This is also due to if cells
grow and grow at a fast rate you get hypoxia because the blood vessels are not keeping up
with the growth and in the tumor cells you get hypoxia which will activate the hypoxia
activated transcription factor HIF-1 which is the TF for many genes involved in the glycolysis
→ So GLUT 1 and GLUT3 are increased if you activate HIF-1
→ So all the enzymes that play a role in the glycolysis are increased when HIF-1 is
activated
→ HIF-1 stimulates blood vessel growth → So the activation of your hypoxia induced TF will
besides increase your glycoses also leads to increase of blood vessel growth making the
tumor more connected to the rest of the body and getting the nutrients from the blood
→ If you have a high glycolysis and high hypoxia there is not much oxygen so there will be
a lot of lactate production to regenerate NAD+
→ The lactate inhibits the local immune system which normally would recognize the tumor
cell, but the local system is now inhibited
→ If you train your muscle under anaerobic conditions this enhances your muscle strength,
because HIF-1 also increases the blood vessel growth in your muscles and increase glycolysis
➢ Summary
1. ATP is the universal currency of energy
2. Glycolysis result in 2 ATP and 2 NADH molecules
3. NAD+ is regenerated by metabolism of pyruvate either via oxidation of Acetyl CoA or by
reduction to lactate or ethanol
4. Glycolysis is regulated at the level of phosphofructokinase, hexokinase and pyruvate
kinase.
➢ The citric acid cycle result in the oxidation of an acetyl unit to 2 CO2
, → Pyruvate is the end of glycolysis
→ Pyruvate has to enter mitochondria and has to be transformed in to Acetyl CoA after
which it can go in to the citric acid cycle in the mitochondria and then will result in the
oxidation of the Acetyl CoA unit in to 2 CO2
➢ Pyruvate Dehydrogenase
→ The first step is from pyruvate to Acetyl CoA by the enzyme pyruvate dehydrogenase
→ These steps will render NADH
→ You can’t make pyruvate from Acetyl CoA because it’s a one direction reaction
➢ Regulation of pyruvate dehydrogenase complex
→ The pyruvate dehydrogenase is highly regulated by the energy status of a cell
→ So if you have amounts of ATP / Acetyl CoA / NADH this all blocks your pyruvate
dehydrogenase
→ So if your cell has plenty of energy you have a low flux from pyruvate to Acetyl CoA
→ If your muscles starts contracting you fast consume your ATP and get a lot of ADP which
then will stimulate the pyruvate dehydrogenase complex to be active and to increase the flux
→ The also increased flux trough glycolysis will increase the amount of pyruvate and that
will also stimulates the pyruvate dehydrogenase
➢ Citric acid cycle
→ The Acetyl CoA will enter the citric acid cycle where the Acetyl CoA will fuse with the
oxaloacetate in to citrate and will go through this cycle
→ The 2 C units of Acetyl CoA are converted to 2x CO2 which will leave the cycle
➢ Coupling of citric acid cycle with oxidative phosphorylation generates ATP
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