Gluconeogenesis Flashcards
What is the most important gluconeogenic tissue?
The LIVER
The KIDNEY has similar capacity but is smaller in size; therefore, does not contribute to the maintenance of BG levels as much
Certain MUSCLE FIBERS have limited gluconeogenesis capacity
(TRUE/FALSE)
Oxaloacetate can leave the mitochondria and go into the cytoplasm freely.
FALSE
It requires transportation
How does OAA leave the mitochondria?
- OAA —–> Malate (via malate dehydrogenase)
- OAA —–> Aspartate (via aspartate aminotransferase
Malate dehydrogenase
Converts OAA —> Malate
So it can be transported out of the mitochondria
Aspartate aminotransferase
Converts OAA —> Aspartate
So it can be transported out of the mitochondria and be converted back to OAA, then PEP in the cytoplasm
What enzyme does muscle tissue lack? Why is this important?
Glucose-6-phosphatase (which catalyzes the last step of the gluconeogenesis pathway)
Why is this important? Glucose-6-P is not able to leave the muscle tissue. So it can be used for glycolysis, or to replenish glycogen stores, but IT CANNOT be released to the blood to maintain BG levels.
What are 3 gluconeogenic intermediates?
- GLYCEROL from the breakdown of triacylglycerol molecules. Which can be converted to DHAP (dihydroxyacetone phosphate), which can be converted to glyceraldehyde-3-P to enter the glycolytic pathway.
- LACTATE via Cori Cycle
- AMINO ACIDS
What is the Cori Cycle?
Lactate produced during anaerobic glycolysis, is released into the blood by exercising SM (or cells w/o MITO- RBCs).
In the Cori Cycle, this lactate is taken up by the LIVER and oxidized to PYRUVATE that is converted to GLUCOSE via GLUCONEOGENESIS, which is released back into circulation.
Define glucogenic amino acids
If catabolism of an AA leads to pyruvate or OAA or any of the other 4-5 carbon compounds in the Krebs Cycle, then glucose synthesis can occur
What 2 AAs are not glucogenic AAs?
LEUCINE
LYSINE
**These are completely ketogenic.
What is the important glucogenic AA?
ALANINE**
What is the alanine cycle?
The connection between the muscle tissue and the liver during times of prolonged fasting or starvation
A way to remove amine groups from the muscle by pyruvate being converted to alanine, which will go to the liver, where the Alanine will be deaminated (amine groups are removed), going through the Urea Cycle.
NOTE: This is high energy; requiring 4 ATP for 2 amine groups.
Once the amine groups are cleaved off, the 2 pyruvate can go through gluconeogenic pathway (costing 6 ATP).
Which Cycle is used for lactate returning to the liver from peripheral tissues?
CORI CYCLE**
From mostly tissues that do not have mitochondria - RBCs
Which Cycle is used for alanine returning to the liver from the peripheral tissues?
ALANINE CYCLE**
From mostly muscle tissues that is going through a fasted or starved state.
What is propionyl-CoA?
3-carbon fragment/product of gluconeogenesis from FAs with an odd number of carbons
It is a precursor for gluconeogenesis because it yields oxaloacetate.
Beta-oxidation typically has XXX number of carbons in our FA chain.
EVEN number, these 2 carbon fragments will enter into the Krebs Cycle
Which BCAAs can be converted to propionyl-CoA?
VALINE
ISOLEUCINE
CHOLESTEROL
What are the non-CHO substrates for gluconeogenesis?
Glucogenic AAs (all except lysine and leucine)
LACTATE
PYRUVATE
GLYCEROL
PROPIONATE (from odd chain FA)
Why is gluconeogenesis important?
- It enables the maintenance of BG levels long after all dietary glucose has been oxidized and stored glycogen has been used up.
- It is essential for tissues that use glucose primarily, such as BRAIN, RBCS, CORNEA, LENS
What are the names of the 3 enzymes in glycolysis that CANNOT go in reverse to perform gluconeogenesis?
- Glucokinase/Hexokinase
- PFK
- Pyruvate kinase
What are the names of the 4 enzymes that are needed for gluconeogenesis that are not part of glycolysis?
Why are these enzymes needed?
- Glucose-6-phosphatase (liver only).
- Fructose 1,6-bisphosphatase
- Pyruvate carboxylase
- PEPCK (Phosphoenolpyruvate carboxykinase)
*The reactions cannot go backwards due to the high energy levels that would be needed.
What is the reaction that GLUCOSE-6-PHOSPHATASE catalyzes?
Glucose-6-P —–> Glucose (in the liver ONLY)
What is the reaction that FRUCTOSE 1,6-BISPHOSPHATASE catalyzes?
Fructose 1,6-bisP —-> Fructose-6-P
What is the reaction that PYRUVATE CARBOXYLASE catalyzes?
Pyruvate —-> OAA (in the MITO)
What is the reaction that PEPCK catalyzes?
OAA —–> PEP (in the CYTOPLASM)
How is gluconeogenesis different in the muscle versus the liver?
Since muscle tissue lacks GLUCOSE-6-PHOSPHATASE, any gluconeogenesis occurring in the muscle produces glucose-6-P, which can be used for glycolysis, OR to help replenish glycogen stores because it CANNOT leave the muscle.
Unlike the liver, where glucose can be released into circulation to help maintain BG levels.
How does the Alanine Cycle contribute to gluconeogenesis?
Glucose is secreted from the liver through gluconeogenesis, which will be taken up by the muscle. It will enter glycolysis, like we have talked about. 2 pyruvate will not enter the Krebs Cycle, rather they will PICK UP 2 AMINE GROUPS (leftover from AA catabolism), this converts PYRUVATE —> ALANINE. Alanine leaves and goes to the LIVER.
In the liver, alanine is diaminated, and the amine groups go to the Urea Cycle (costing 4 ATP for 2 amine groups). The 2 pyruvate go through gluconeogenesis being converted back to GLUCOSE (costing 6 ATP).
How does the Cori Cycle contribute to gluconeogenesis?
During anaerobic glycolysis, LACTATE is released into the blood by exercising SM and cells that lack mitochondria (RBCs). In the Cori Cycle, this lactate is taken up by the liver and oxidized to PYRUVATE, that is converted to GLUCOSE via gluconeogenesis, which is released back to circulation.
How is GLYCEROL used in gluconeogenesis?
Phosphorylation of glycerol produces glycerol-3-P, which is converted to DHAP (dihydroxyacetone phosphate), an intermediate of gluconeogenesis, producing 1/2 glucose, OR lactate.
How are odd number FAs used in gluconeogenesis?
PRIOPIONYL-COA is a precursor for gluconeogenesis because it yields OAA.
Typically, beta-oxidation of even number FA produces acetyl-CoA, which cannot be converted to pyruvate or OAA, so it is impossible to make glucose from FAs, except in the case of odd-chain carbon FAs like propionyl-CoA.
