9.6 Gluconeogenesis

Question 1

Important substrates for gluconeogenesis

Answer 1

• Glycerol 3-phosphate (from stored fats, or triacylglycerols, in adipose tissue)
• Lactate (from anaerobic glycolysis)
• Glucogenic amino acids (from muscle proteins)

Question 2

What countterregulatory hormones act to raise blood sugar lvls by stimulating glycogenolysis and gluconeogenesis?

Answer 2

• glucagon, epinephrine, cortisol, and growth hormone

Question 3

Glucogenic amino acids (all
except leucine and lysine)

Answer 3

• can be converted into intermediates that feed into gluconeogenesis

Question 4

ketogenic amino acids

Answer 4

• can be converted into ketone
  bodies, which can be used as an alternative fuel, particularly during periods of prolonged starvation

Question 5

Is it possible to convert acetyl-CoA back to glucose?

Answer 5

No,

Question 6

How is glucose produced in the liver durng gluconeogenesis?

Answer 6

to produce glucose in the liver during gluconeogenesis, fatty acids must be burned to provide this energy, stop the
forward flow of the citric acid cycle, and produce massive amounts of OAA that can eventually lead to glucose production for the rest of the body.

Question 7

What is the pathway for Pyruvate Carboxylase to make OAA?

Answer 7

Acetyl coA (activates) -> Pyruvate Carboxylase -> OAA (reduced to) -> malate so can leave mitochondrion -> Oxidized to OAA in cytoplasm

Question 8

Phosphoenolpyruvate carboxykinase (PEPCK)

Answer 8

• in the cytoplasm
• induced by glucagon and cortisol, which generally act to raise blood sugar levels
• the combination of pyruvate carboxylase and PEPCK are used to circumvent the
  action of pyruvate kinase by converting pyruvate back into PEP

Question 9

Fructose-1,6-Bisphosphatase

Answer 9

• in the cytoplasm
• a key control point of gluconeogenesis and represents the rate-limiting step of the process
• reverses the action of phosphofructokinase-1, the rate-limiting step of glycolysis, by removing phosphate from fructose 1,6-bisphosphate to
  produce fructose 6-phosphate.
• activated by ATP and inhibited by AMP and fructose 2,6-bisphosphate

Question 10

Difference between how Glucagon and Insulin react with Fructose 2,6-bisphosphate (F2,6-BP)?

Answer 10

• glucagon will lower F2,6-BP and stimulate gluconeogenesis, whereas insulin will increase F2,6-BP and inhibit gluconeogenesis.

Question 11

Fructose 2,6-bisphosphate (F2,6-BP)

Answer 11

• thought of as a marker for satisfactory energy levels in liver cells
• helps these cells override the inhibition of phosphofructokinase-1 that occurs when high levels of acetyl-CoA are formed, signaling to the liver cell that it should shift its function from
  burning to storing fuel

Question 12

Glucose-6-Phosphatase

Answer 12

• found only in the lumen of the endoplasmic reticulum in liver cells
• transported into the ER, and
  free glucose is transported back into the cytoplasm, from where it can diffuse out of the cell using GLUT transporters
• Absence in skeletal muscle means that muscle glycogen cannot serve as a source of blood glucose and rather is for use only within the muscle
• used to circumvent glucokinase and hexokinase, which convert glucose to glucose 6-phosphate

Question 13

During periods of low blood sugar what do adipose tissues do?

Answer 13

• releases these fatty acids by breaking down triacylglycerols to glycerol (which can also be
  converted to the gluconeogenic intermediate DHAP) and free fatty acids.

Question 14

Can acetyl-CoA from fatty acids be converted into glucose?

Answer 14

• No, but it can be converted into ketone bodies as an alternative fuel for cells,
  including the brain.

Question 15

Is glucose produced by the liver an energy source for the liver?

Answer 15

• No, gluconeogenesis does not represent an energy source for the liver. Gluconeogenesis requires expenditure of ATP that is provided by β-oxidation of fatty acids