9. Gluconeogenesis, PPP Flashcards
Five characteristics of the pentose phosphate pathway (PPP)?
This pathway obtains pentoses (C5): building blocks RNA + DNA
Provides 50% of NADPH, needed for fatty acid synthesis. Highly expressed at sites for fatty acid synthesis (liver, mammary gland, adipose)
- Only source of NADP for red blood cells
Connects Ch metabolism with lipid metabolism
- substrate is glucose
NAD and NADP: conversible?
NAD vs NADP: cannot simply exchange these two or convert them to one another. NADP really needs to be synthesized by PPP
NADP has a ..
NADP: phosphorylated OH group
Look at the metabolic map. How many gl-6-p are needed for the PPP ? How many riboses are obtained?
3 mol, 3 mol
Explain the pathway using the map.
You need to start with three mol glucose.
Then, you get three mol g-6-p, to obtain three riboses (which is the natural pathway: 3x)
Then, you get the intermediate gl-3-p. Detour to the riboses. Release 3 x 2 NADPH and 3x CO2. Then two intermediates of glycolysis released: one glyceraldehyde-3-p and two fr-6-p. Can be used for ATP production following glycolysis.
After ribulose-5-p, there are C’s exchanges. Explain this process.
- 2 glucoses yield 2 ribuloses (C5).
- They start to exchange C’s: one converts in C7 and the other in C3.
- Exchange again until one has C4 and one has C6.
- First product yield: (C6) fr-6-p
- Another glucose is used, another C5 is created
- Interacts with C4: yield one C6 and one C3.
Second products yielded: (C6) fr-6-p and (C3) gl-3-ph
Now, what is yielded in total by PPP?
1x C3
2x C6
3x 2= 6 NADPH
3x CO2
PPP vs glycolysis: ATP yield.
PPP yields 1x C3 (Ga-3-p) and 2x C6 (fr-6-p). = 6 NADPH
Glycolysis: to reach the same metabolites
Yield: 2x C6 (fr-6-p) = 0 ATP
Yield: 2x ga-3-p with one mol of glucose = -1 ATP
Therefore, one can be used in oxidation.
Oxidation of one ga-3-p = 16 ATP.
Total = 16-1 = 15 ATP.
Choosing whether to make 6 NADPH or 15 ATP is dependent on..
e.g. amount of glucose in the cells.
If there is a peak, either glycogen will be stored or NADPH will be produced.
What are neutral energetics vs substrate cycle?
Neutral energetics (mass driven, equilibrium)
= Energy invested in the forward reaction is released in the backward reaction. Net result = 0
Substrate cycle (tourniquet principle: go in ‘pay’/go out ‘free’)
= Energy invested in the forward reaction is not released in the backwards reaction
Glycolysis:
1 m Glucose -> 2 m pyruvate
So, gluconeogenesis = ..
2 m pyruvate -> 1 m glucose
What are the neutral reactions in glycolysis and gluconeogenesis?
ga-3-p > 1,3bip > 3-phosphoglycerate
Energy loss of glucose -> 2 pyruvate -> glucose (glucose substrate cycling)?
-6 ATP
(down: +5 ATP)
(up: -11 ATP)
Pyruvate can go a lot of directions, namely..
For what?
- Acetly-CoA: glycolysis
- Lactate: anaerobic oxidation
- OAA: gluconeogenesis
Gluconeogenesis: starts from pyruvate:
Cells have to switch:
Pyruvate -> acetyl-CoA
or:
Pyruvate -> oxaloacetate
What does this depend on?
High acetyl-CoA = change to oxaloacetate
High AMP (signaling low energy) = low ATP = stimulation citric acid cycle = condensation oxaloacetate + Acetyl-CoA
Low AMP = high ATP = stimulation of gluconeogenesis, oxaloacetate is converted to PEP; inhibition glycolysis
Pasteur effect: 15x more glucose needed in anaerobic oxid. to obtain same amount of ATP when finishing TCA cycle.
Why do cells switch to lactate glycolysis when in need? Under which conditoins was it used again?
it is very very fast.
- No oxygen
- No mitochondria
What type of NADH does lactate pathway use? What happens to the NAD+?
Cytosolic.
use it in conversion pyruvate to lactate and NAD+ is reused upstream. So you can immediately cycle NADHc to release lactate, which is shuttled out of the muscle cell
How much ATP is produced / glucose with pyruvate?
2 ATP
How much NADH is USED when converting pyruvate to lactate if the pyruvate is coming from a glucose molecule?
What happens with the NAD+?
When the lactate then enters the liver, ..
- 2 NADHc, because you get 2 lactate per 2 pyruvate per 1 glucose.
- NAD+ is reused in converting glucose to pyruvate, which yields 2 NADHc
- When the lactate then enters the liver, it is converted to pyruvate again releasing 2 NADHc
- 2 NADHc is used in gluconeogenesis
Where does lactate go?
It then goes into the liver, where lactate is used to recycle it into glucose, which can be released into circulation.
What is the Cori cycle?
Recycling of lactate
- glycolysis in muscle (1 glucose -> 2 pyruvate -> 2 lactate)
- Gluconeogenesis in the liver (2 lactate -> 2 pyruvate -> 1 glucose)
Then glucose will go to muscle again … creating a cycle
p.94
Cycling of lactate: ATP in muscle vs liver?
Muscle: glucose -> 2 ATP + lactate
Liver: 2 lactate + 8 ATP -> glucose
Extra costs: 6 ATP
Energy goes into heat
Some tissues better adapt to anaerobic conditions. Examples?
- RBCs do not contain mitochondria and only use the lactic acid pathway.
- Occurs in skeletal muscles and heart when ratio of oxygen supply to oxygen need falls below critical level.
What happens when cardiac muscle expires anaerobically?
Cardiac muscle normally respires aerobically:
– Myocardial ischemia occurs under anaerobic conditions.
Ratio ATP yield in ATP of aerobic and anaerobic breakdown of glucose?
30/2 = 15x
After 5 days high fat vs low fat diet in mice they saw..
Change in certain genes: 5 days diet have huge effect on metabolism at tissue level
How many Cs does propionic acid have?
C3
Direct oxidation of propionic acid (C3 -> C4 acetyl-CoA so apparently now you need 2x propionic acid).
How much ATP?
2 x 13.5 = 27 ATP
Direct = convert to PEP -> acetyl- CoA -> TCA cycle
How much ATP with propionic acid if you use indirect oxidation via glucose-6-p? Or glucose? Or glycogen?
Gl-6-p = 26 ATP
glucose = 25 ATP
Glycogen = 25 ATP
