Gluconeogenesis

Question 1

What is the most important gluconeogenic tissue?

Answer 1

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

Question 2

(TRUE/FALSE)

Oxaloacetate can leave the mitochondria and go into the cytoplasm freely.

Answer 2

FALSE

It requires transportation

Question 3

How does OAA leave the mitochondria?

Answer 3

1. OAA —–> Malate (via malate dehydrogenase)
2. OAA —–> Aspartate (via aspartate aminotransferase

Question 4

Malate dehydrogenase

Answer 4

Converts OAA —> Malate

So it can be transported out of the mitochondria

Question 5

Aspartate aminotransferase

Answer 5

Converts OAA —> Aspartate

So it can be transported out of the mitochondria and be converted back to OAA, then PEP in the cytoplasm

Question 6

What enzyme does muscle tissue lack? Why is this important?

Answer 6

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.

Question 7

What are 3 gluconeogenic intermediates?

Answer 7

1. 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.
2. LACTATE via Cori Cycle
3. AMINO ACIDS

Question 8

What is the Cori Cycle?

Answer 8

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.

Question 9

Define glucogenic amino acids

Answer 9

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

Question 10

What 2 AAs are not glucogenic AAs?

Answer 10

LEUCINE

LYSINE

**These are completely ketogenic.

Question 11

What is the important glucogenic AA?

Answer 11

ALANINE**

Question 12

What is the alanine cycle?

Answer 12

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).

Question 13

Which Cycle is used for lactate returning to the liver from peripheral tissues?

Answer 13

CORI CYCLE**

From mostly tissues that do not have mitochondria - RBCs

Question 14

Which Cycle is used for alanine returning to the liver from the peripheral tissues?

Answer 14

ALANINE CYCLE**

From mostly muscle tissues that is going through a fasted or starved state.

Question 15

What is propionyl-CoA?

Answer 15

3-carbon fragment/product of gluconeogenesis from FAs with an odd number of carbons

It is a precursor for gluconeogenesis because it yields oxaloacetate.

Question 16

Beta-oxidation typically has XXX number of carbons in our FA chain.

Answer 16

EVEN number, these 2 carbon fragments will enter into the Krebs Cycle

Question 17

Which BCAAs can be converted to propionyl-CoA?

Answer 17

VALINE
ISOLEUCINE
CHOLESTEROL

Question 18

What are the non-CHO substrates for gluconeogenesis?

Answer 18

Glucogenic AAs (all except lysine and leucine)

LACTATE

PYRUVATE

GLYCEROL

PROPIONATE (from odd chain FA)

Question 19

Why is gluconeogenesis important?

Answer 19

1. It enables the maintenance of BG levels long after all dietary glucose has been oxidized and stored glycogen has been used up.
2. It is essential for tissues that use glucose primarily, such as BRAIN, RBCS, CORNEA, LENS

Question 20

What are the names of the 3 enzymes in glycolysis that CANNOT go in reverse to perform gluconeogenesis?

Answer 20

1. Glucokinase/Hexokinase
2. PFK
3. Pyruvate kinase

Question 21

What are the names of the 4 enzymes that are needed for gluconeogenesis that are not part of glycolysis?

Why are these enzymes needed?

Answer 21

1. Glucose-6-phosphatase (liver only).
2. Fructose 1,6-bisphosphatase
3. Pyruvate carboxylase
4. PEPCK (Phosphoenolpyruvate carboxykinase)

*The reactions cannot go backwards due to the high energy levels that would be needed.

Question 22

What is the reaction that GLUCOSE-6-PHOSPHATASE catalyzes?

Answer 22

Glucose-6-P —–> Glucose (in the liver ONLY)

Question 23

What is the reaction that FRUCTOSE 1,6-BISPHOSPHATASE catalyzes?

Answer 23

Fructose 1,6-bisP —-> Fructose-6-P

Question 24

What is the reaction that PYRUVATE CARBOXYLASE catalyzes?

Answer 24

Pyruvate —-> OAA (in the MITO)

Question 25

What is the reaction that PEPCK catalyzes?

Answer 25

OAA —–> PEP (in the CYTOPLASM)

Question 26

How is gluconeogenesis different in the muscle versus the liver?

Answer 26

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.

Question 27

How does the Alanine Cycle contribute to gluconeogenesis?

Answer 27

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).

Question 28

How does the Cori Cycle contribute to gluconeogenesis?

Answer 28

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.

Question 29

How is GLYCEROL used in gluconeogenesis?

Answer 29

Phosphorylation of glycerol produces glycerol-3-P, which is converted to DHAP (dihydroxyacetone phosphate), an intermediate of gluconeogenesis, producing 1/2 glucose, OR lactate.

Question 30

How are odd number FAs used in gluconeogenesis?

Answer 30

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.