Gluconeogenesis - General

Question 1

What is the primary function of gluconeogenesis?

Answer 1

To assist in maintaining adequate glucose levels in the blood.

Question 2

Besides pyruvate, what are three other gluconeogenic precursors. What steps will each enter?

Answer 2

1. Lactate: replaces pyruvate
2. Some amino acids: replaces pyruvate or oxaloacetate
3. Glycerol: replaces DHAP

Question 3

How many high phosphoryl transfer potential groups are used during gluconeogenesis? Which are they?

Answer 3

6. 4 ATP and 2 GTP.

Question 4

Where does gluconeogenesis occur in the body?

Answer 4

Mostly in the liver, somewhat in the kidneys.

Question 5

General rule: when glucose is abundant, _____ is favoured. When glucose is scarce, _____ is favoured.

Answer 5

Glycolysis; gluconeogenesis.

Question 6

What challenge does oxaloacetate pose in terms of gluconeogenesis? How is this overcome?

Answer 6

Oxaloacetate does not have a transporter in the mitochondria. To remedy this, it is converted to malate, shipped out, and reconverted to oxaloacetate.

Question 7

Pyruvate carboxylase catalyzes which reaction in gluconeogenesis? What two groups does it require and why?

Answer 7

The conversion of pyruvate to oxaloacetate.

It requires:

• Biotin: covalently bound prosthetic group, carries CO₂
• Acetyl CoA: obligate allosteric activator, carboxylation does not occur without it

Question 8

Glycolysis and gluconeogenesis are _____ regulated.

Answer 8

Reciprocally.

Question 9

What reaction acts as the major point of regulation?

Answer 9

Fructose-1,6-bisphosphate to fructose-6-phosphate.

Question 10

There are 6 things (that we talked about) that regulate gluconeogenesis. What are they?

Answer 10

Activate: citrate, ATP, alanine Inhibit: ADP, AMP, fructose-1,6-bisphosphate

Question 11

How do AMP and fructose-2,6-bisphosphate regulate gluconeogenesis?

Answer 11

They activate phosphofructokinase and inhibit fructose-1,6-bisphosphatase, slowing gluconeogenesis.

Question 12

How does citrate regulate gluconeogenesis?

Answer 12

Inhibits PFK and stimulates fructose-1,6-bisphosphatase.

Question 13

How do ATP and alanine regulate gluconeogenesis?

Answer 13

They inhibit pyruvate kinase.

Question 14

How does ADP regulate gluconeogenesis?

Answer 14

Blocks conversion of pyruvate to phosphoenolpyruvate.

Question 15

Without this, gluconeogenesis would be endergonic and would not occur. Instead, it is exergonic.

Answer 15

Reaction coupling.

Question 16

How do blood sugar levels influence the concentration of fructose-2,6-bisP?

Answer 16

Blood sugar determines the activities of PFK and fructose-1,6-bisphosphatase, which in turn influence the concentration of fructose-2,6-bisP.

Question 17

How does low blood sugar determine the activities of PFK and fructose-1,6-bisphosphatase? What hormone is involved and how does it act to regulate the enzymes?

Answer 17

• A serine residue in the regulatory chain becomes phosphorylated due to the presence of the hormone glucagon.
• When phosphorylated, the phosphatase (FBPase) domain is activated and the kinase (PFK) domain is inhibited.
  
  • This lowers the concentration of fructose-2,6-bisP in the cell increasing flux to gluconeogenesis.

Question 18

How does high blood sugar determine the activities of PFK and fructose-1,6-bisphosphatase? What hormone is involved?

Answer 18

• When insulin is high, there is less phosphorylation.
  
  • This increases kinase activity and inhibits phosphorylase activity.
• The subsequent increase of fructose-2,6-bisP causes a flux shift to glycolysis.

Question 19

The Cori Cycle converts lactate in _____ tissue to _____ in _____ tissue using the enzyme _____. This replenishes glucose levels, increasing flux to _____.

Answer 19

Muscle; glucose; liver; lactate dehydrogenase; glycolysis.