Metabolism IV: Gluconeogenesis

Question 1

Gluconeogenesis involves the synthesis of ________ from ________ precursors.

Answer 1

glucose; non-carbohydrate

Question 2

Where does gluconeogenesis take place?

Answer 2

in the liver (and to a small extent, in the kidney)

Question 3

How many ATP does gluconeogenesis require?

Answer 3

6 ATP

Question 4

Pyruvate is converted to ________ in a two-step process via ________, which can be viewed as a(n) _______ form of pyruvate.

Answer 4

phosphoenolpyruvate (PEP); oxaloacetate; activated

Question 5

Which molecules are involved in the conversion of pyruvate to PEP?

Answer 5

bicarbonate and biotin (a cofactor); this requires ATP expenditure

Question 6

Which are the major gluconeogenic precursors and their sources?

Answer 6

• lactate from general metabolism, RBC metabolism, muscle metabolism
• glucogenic amino acids (ex: alanine, aspartate) from overnight degradation of muscle amino acids
• glycerol from degradation of adipose tissue TAGs

Question 7

The neonate’s brain is highly dependent on glucose from which source, and why can this be a problem?

Answer 7

• from glycogen degradation and gluconeogenesis
• can be a problem bc it takes a few hours to induce PEP carboxykinase (needed to make glucose from lactate or alanine feeding into pyruvate), which puts the infant at risk for hypoglycemia

Question 8

Can acetyl-CoA be used to make glucose once it is made?

Answer 8

No, it is committed to either fatty acid synthesis or the Krebs cycle (cannot be used for gluconeogenesis).

Question 9

Which are the 4 enzymes used to reverse the irreversible steps of glycolysis?

Answer 9

1. Pyruvate carboxylase (pyruvate–>oxaloacetate)
2. PEP carboxykinase (oxaloacetate–>PEP)
3. Fructose-1,6-bisphosphatase (F-1,6-BP–>F6P)
4. Glucose-6-phosphatase (G6P–>glucose)

Question 10

Where is pyruvate carboxylase found? How does it get there?

Answer 10

It is found in the mitochondrial matrix, and it enters the mitochondria via a translocase (this process requires biotin and bicarb)

Question 11

What is the effect of NADH level on the amount of lactate?

Answer 11

• increased NADH=increased lactate formation

- decreased NADH=decreased lactate formation

Question 12

What happens when pyruvate carboxylase is deficient?

Answer 12

Lack of enzyme activity leads to buildup of pyruvate in the plasma, which is then converted to lactate by the enzyme lactate dehydrogenase (this leads to an elevated level of lactic acid in the plasma).

Question 13

What is the Cori cycle also known as, and what is the main principle?

Answer 13

glucose-lactate cycle:
RBCs (and skeletal muscles) undergo anaerobic glycolysis, leading to the production of lactate, which diffuses into the liver and feeds into gluconeogenesis; glucose is formed as a result, and it diffuses out of the liver and into RBCs to be cyclically converted back to lactate

Question 14

What is the alanine cycle also known as, and what is the main principle?

Answer 14

Cahill cycle, or glucose-alanine cycle:
muscle cells undergo glycolysis and convert the resulting pyruvate into alanine; alanine diffuses out of muscle cells and into the liver where it A) enters the urea cycle and B) is converted back to pyruvate–> gluconeogenesis–>glucose; glucose diffuses back into muscle cells to re-start the cycle

Question 15

What is the alanine cycle also known as, and what is the main principle?

Answer 15

Cahill cycle, or glucose-alanine cycle:
muscle cells undergo glycolysis and convert the resulting pyruvate into alanine; alanine diffuses out of muscle cells and into the liver where it A) enters the urea cycle and B) is converted back to pyruvate–> gluconeogenesis–>glucose; glucose diffuses back into muscle cells to re-start the cycle

Question 16

Why is the glucose-6-phosphatase enzyme found in the liver, kidney, and intestines but NOT in muscle?

Answer 16

This is because we want to get glucose out of the liver, kidney, and intestines once we mobilize our glycogen stores, whereas we want to retain glucose inside muscle cells because they use glucose as their energy source.