Gluconeogenesis - General Flashcards
What is the primary function of gluconeogenesis?
To assist in maintaining adequate glucose levels in the blood.
Besides pyruvate, what are three other gluconeogenic precursors. What steps will each enter?
- Lactate: replaces pyruvate
- Some amino acids: replaces pyruvate or oxaloacetate
- Glycerol: replaces DHAP
How many high phosphoryl transfer potential groups are used during gluconeogenesis? Which are they?
- 4 ATP and 2 GTP.
Where does gluconeogenesis occur in the body?
Mostly in the liver, somewhat in the kidneys.
General rule: when glucose is abundant, _____ is favoured. When glucose is scarce, _____ is favoured.
Glycolysis; gluconeogenesis.
What challenge does oxaloacetate pose in terms of gluconeogenesis? How is this overcome?
Oxaloacetate does not have a transporter in the mitochondria. To remedy this, it is converted to malate, shipped out, and reconverted to oxaloacetate.
Pyruvate carboxylase catalyzes which reaction in gluconeogenesis? What two groups does it require and why?
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
Glycolysis and gluconeogenesis are _____ regulated.
Reciprocally.
What reaction acts as the major point of regulation?
Fructose-1,6-bisphosphate to fructose-6-phosphate.
There are 6 things (that we talked about) that regulate gluconeogenesis. What are they?
Activate: citrate, ATP, alanine Inhibit: ADP, AMP, fructose-1,6-bisphosphate
How do AMP and fructose-2,6-bisphosphate regulate gluconeogenesis?
They activate phosphofructokinase and inhibit fructose-1,6-bisphosphatase, slowing gluconeogenesis.
How does citrate regulate gluconeogenesis?
Inhibits PFK and stimulates fructose-1,6-bisphosphatase.
How do ATP and alanine regulate gluconeogenesis?
They inhibit pyruvate kinase.
How does ADP regulate gluconeogenesis?
Blocks conversion of pyruvate to phosphoenolpyruvate.
Without this, gluconeogenesis would be endergonic and would not occur. Instead, it is exergonic.
Reaction coupling.
How do blood sugar levels influence the concentration of fructose-2,6-bisP?
Blood sugar determines the activities of PFK and fructose-1,6-bisphosphatase, which in turn influence the concentration of fructose-2,6-bisP.
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?
- 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.
How does high blood sugar determine the activities of PFK and fructose-1,6-bisphosphatase? What hormone is involved?
- 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.
The Cori Cycle converts lactate in _____ tissue to _____ in _____ tissue using the enzyme _____. This replenishes glucose levels, increasing flux to _____.
Muscle; glucose; liver; lactate dehydrogenase; glycolysis.
