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Summary Food and Metabolism
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Food and MetabolismLecture 1 – Energy and carbohydrate metabolism
Metabolism is the sum of catabolic and anabolic reactions in a cell. In the catabolic pathways food is
broken down in smaller blocks and in the anabolic pathway bigger molecules are build of this smaller
blocks.
- Catabolism is the breaking down of compounds to release energy. Anabolism is the building
of compounds, which uses energy.
ATP, the universal currency of free energy ATP to ADP results in 30 KJ/mol.
The ATP need to be regenerate and this is done by the oxidation of fuel
molecules or photosynthesis.
Sources of ATP during exercise
In muscles creatine phosphate is broken down to restore some energy in very
short time.
After that your creatine phosphate is depleted and you need other sources, like the aerobic and
anaerobic metabolism.
Stages of catabolism
The breakdown of glucose will happen in three steps;
1. The breakdown of the bigger molecules (fats/proteins) into smaller
molecules), no ATP production.
2. You convert you glucose into acetyl CoA, a little ATP is produced.
3. Acetyl CoA comes into the Citric acid cycle, here a lot of ATP is produced.
Glycolysis; the main pathway in which glucose is converted into Acetyl CoA to go
into the Citric acid cycle.
First phase of glycolysis cost ATP
Glucose is transported into the (muscle)cell by glucose transporters.
The first step of the metabolism is done by hexokinase that add a
phosphate group of ATP to glucose and convert it into Glucose-6-
phosphate, so cost ATP.
This Glucose-6-phosphate can co further into the glycolysis where it
will turn into Fructose-6-phosphate and another phosphate group will
be added from ATP. Phosphofructokinase add a phosphate to
fructose-6-phosphate and convert it into Fructose 1,6-biphosphate, so
cost ATP.
This fructose 1,6-biphosphate will be split into two C3 molecules and
this will enter the second phase of the glycolysis.
1
,Phase 2 of glycolysis generates ATP
The two C3 molecules (Glyceraldehyde 3-phosphate) go into 2 molecules of
1,3-Bisphosphoglycerate that is converted to 3-Phosphoglycerate by
phosphoglycerate kinase, this generates ATP.
Then at the almost end you get phosphoenolpyruvate that is converted
into pyruvate by pyruvate kinase, this generates ATP.
Net generation of glycolysis is 2 ATP and 2 NADH.
ATP production by glycolysis
During glycolysis glucose is converted into pyruvate. If you have pyruvate
you can either turn this into lactate (no oxygen) or pyruvate can go into the
mitochondria in the citric acid cycle.
NAD+ is regenerated through metabolism of pyruvate
If you don’t regenerate NAD+ the glycolysis stops, so you have to generate NAD+.
This can be done in 3 methods (in our body mostly 2);
1. Low oxygen (type IIb muscle fibers/red blood cells/microbes) pyruvate is turned into lactate.
This lactate can move from the muscle to the liver where it can be regenerated into glucose.
2. Enough oxygen the acetyl CoA can be further oxidized in the cycle and you can also
regenerate your NAD+.
3. Yeast/microbes can also make ethanol from acetaldehyde to generate NAD+.
Regulation of glycolysis during high ATP
At rest when you have a low consumption of ATP, you have high ATP levels.
These high levels will block the pyruvate kinase and the PFK and this will lead to
an increase of Fructose 6-phosphate/Glucose 6-phosphate.
The Glucose 6-phosphate have a negative feedback on himself by blocking
hexokinase. Because at rest you don’t need much ATP.
Regulation of glycolysis during low ATP
However when you start sprinting the amount of ATP you muscle need will
increase by 100 fold, this switch can be done really fast. If you have your cell
depleted of energy you get from ATP -> ADP -> AMP, and this AMP will signal
and stimulate the PFK to convert Fructose 6-phosphate into Fructose – 1,6-
biphosphate.
So the Glucose-6-phosphate that normally inhibit hexokinase stops inhibiting
himself. And the Fructose-1,6-biphosphate stimulates the pyruvate kinase.
Rapidly growing cells use glycolysis
Not only your muscle use a lot of glucose but also the rapid growing cells uses a
lot of glucose to growth, so in our body this can be tumor cells.
- PET scan; tumor can be visualized due to high glucose intake. You see the radio labeled
deoxy-glucose that is taken up by all cells that use glucose. So you can see tumors.
2
,Hypoxia alters gene expression and increase flux through glycolysis
The tumor cells are highly depending on the glycolysis for their energy. But when cells growth on a
high rate you get hypoxia, so in the tumor cells you get hypoxia. And this hypoxia will activate HIF-1,
transcriptional regulator of many genes involved in the glycolysis (hexokinase). HIF-1 also stimulates
blood vessel growth making the tumor more connected to the rest of the body.
- If you have a high glycolysis with hypoxia you don’t have enough oxygen there so you have a
high lactate production. High lactate production -> inhibition of local immune system.
- This can happen in normal situations like in anaerobic exercise training -> enhance muscle
strength. Your muscles becomes stronger because it enhances your blood-vessel growth and
glycolysis.
Summary
- ATP is the universal currency of energy.
- Glycolysis result in 2 ATP and 2 NADH molecules.
- NAD+ is regenerated by metabolism of pyruvate either via oxidation of Acetyl CoA or by
reduction of lactate or ethanol.
- 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
At the end of the glycolysis you get pyruvate. This pyruvate has to enter
the mitochondria and has to be transformed into Acetyl CoA that can go
into the citric acid cycle.
- Citric acid cycle (in mitochondria); oxidation Acetyl CoA into
two CO2.
Pyruvate dehydrogenase (in mitochondria)
The first step is from pyruvate into Acetyl CoA; this is done by pyruvate
dehydrogenase in the mitochondria. The steps will render NADH, this is an irreversible reaction.
- So you can’t make from Acetyl CoA Pyruvate using this process.
Regulation of pyruvate dehydrogenase complex
the pyruvate dehydrogenase complex is highly regulated by the energy
status of the cell. So if you have high amount of ATP, Acetyl CoA and
NADH it blocks PDH.
If you muscle starts contracting, you start to sprint, your muscle start to
consume all your ATP. Now you get ADP and pyruvate that will stimulate
PDH to be active and increase the flux.
Citric acid cycle
The Acetyl CoA will enter the citric acid cycle where Acetyl CoA will fuse with
the oxaloacetate into citrate. The two carbon units of the Acetyl CoA are
converted into 2 CO2.
➔ Outcome 2 CO2, 3 NADH, ATP and FADH2.
➔ 8 electrons are stored.
3
, Coupling of citric acid cycle with oxidative phosphorylation generates ATP
- The oxidative phosphorylation and the electron transport chain
generate a gradient of protons in the mitochondria. And this will
drive the ATP synthesis.
Electrons flow through the electron transport chain powering proton
pumping and results in the reduction of O2 into H2O.
The electron transport chain generates a proton gradient, which is used to
synthesize ATP.
- 1 NADH = 2,5 ATP
- 1 FADH2 = 1,5 ATP
Net yield of one glucose oxidation
- First you have the glucose into pyruvate; 2 ATP and 2 NADH. Here
each NADH produces 1,5 ATP because of transport into mitochondria.
- Second you get the pyruvate into Acetyl CoA; 2 NADH.
- Citric acid cycle happens two times because you have two pyruvate
and two Acetyl CoA; 6 NADH, 2 FADH2, 2 ATP.
- And if you convert this with the formula the total is 30 ATP of 1
glucose.
Uncoupling proteins decrease the proton gradient resulting in decreased ATP synthesis
the efficiency depends on other factors, like the uncoupling proteins. In
the mitochondria you also have proteins like UCP-1 which decreases the
protein gradient, resulting in a decreased ATP synthesis.
- This protein is located in the matrix of the mitochondria and it can
leaks away protons.
- It goes against the gradient of course, and therefore it uncouples
the ATP production from the glucose oxidation.
- This is done in brown adipose tissue, because fatty acids here can activate the UCP-1
channel.
UCP1 is important in brown fat
- The leakages of protons and the disruption of the connection between the glucose oxidation
and ATP synthesis results in heat formation.
- This heat formation is important in hibernating animals, if they need wake-up again their
temperature have to go up.
- This is also present in babies because they have a large surface area, so loose a lot of
warmth. But they also have brown fat for producing heat.
- Brown and beige adipocytes are active in adults; the amount is decreased but it is still
present. This can be activated with cold, that uses a little bit energy.
- People who life in colder climates have increased brown fat.
- People with obesity have more white fat instead of brown fat.
Summary;
1. Pyruvate dehydrogenase connects the glycolysis with the citric acid cycle.
2. The citric acid cycle oxidized acetyl-units to CO2. This results in ATP, 3 NADH and FADH2.
3. Coupling of the citric acid cycle with the oxidative phosphorylation generates ATP.
4. The electron transport chain generates a proton gradient that powers the synthesis of ATP.
5. Uncoupling proteins (UCPs) in the mitochondria uncouple oxidative phosphorylation from
ATP synthesis to generate heat.
4
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