Bio 30 Gluconeogenesis

Question 1

What is the main purpose of gluconeogenesis?

Answer 1

To maintain the blood glucose levels during fasting. It provides the energy that the RBC’s and the brain need to function since they cannot use fat like other cells to produce energy.

Question 2

Describe very general lipolysis reaction.

Answer 2

Lipolysis is the breakdown of TAG’s into glycerol and fatty acids.

Question 3

In very general terms, what is beta-oxidation?

Answer 3

Breakdown of fatty acids into acetyl-coa, NADH, FADH2

Question 4

In general terms, what is ketogenesis?

Answer 4

Conversion of acetyl-coa into ketones for export.

Question 5

Where does gluconeogenesis occur?

Answer 5

Only in the liver and kidney cortex.

Question 6

Does gluconeogenesis produce or use energy?

Answer 6

It uses energy to build an energy rich molecule that can then be used to be exported. It requires 4 ATP, 2 GTP, 2 NADH for each glucose.

Question 7

What are the precursors for gluconeogenesis?

Answer 7

Amino Acids (to make pyruvate)
Lactate (to make pyruvate)
Glycerol (why?)
Propionyl-CoA (from odd chain AA’s to make succinyl-CoA)

Question 8

What are the regulatory enzymes for gluconeogenesis?

Answer 8

Pyruvate Carboxylase (pyruvate–>OAA)
PEP Carboxykinase (OAA–>PEP)
FBPase-1 (Rate limiting, F1,6bisP–>F6P)
G6Pase (G6P–>Glucose)

Question 9

How is blood glucose homeostasis maintained over the five phases of time post a mixed meal?

Answer 9

Phase I (0-4hrs): dietary carbs
Phase II (5-16hrs): glycogen mostly, little gluconeogenesis
Phase III (16-24hrs): liver gluconeogenesis mostly, little glycogen
Phase IV (>24hrs): 50/50 liver and kidney gluconeogenesis
Phase V (>2days): Same

Question 10

What are the major fuel sources for the cells of the body in the five phases after a meal?

Answer 10

Phase I (0-4hrs): dietary carb oxidation
Phase II (5-16hrs): fatty acid oxidation
Phase III (16-24hrs): fatty acids, start to see little ketone use
Phase IV (>24hrs): fatty acid oxidation and more significant ketone use
Phase V (>2days): Same

Question 11

Describe the first regulatory step of gluconeogenesis involving pyruvate carboxylase.

Answer 11

Pyruvate + ATP + CO2–>OAA + ADP
Requires Biotin to attach the CO2
Activated by Acetyl-CoA
Has two functions: Prime TCA cycle, and provide OAA for gluconeogenesis

Question 12

In the fasting state, will pyruvate in the liver be used more for TCA priming or gluconeogenesis?

Answer 12

Because of beta oxidation, NADH and ATP will build up and inhibit ICDH which will slow the TCA cycle significantly. This causes most of the OAA from the pyruvate to be used for gluconeogenesis.

Question 13

How does OAA get from the mitochondria to the cytosol?

Answer 13

Through the malate-aspartate shuttle.

Question 14

Describe the reaction that converts OAA to PEP.

Answer 14

In cytosol
Uses PEP carboxykinase to decarboxylate and phosphorylate OAA to become PEP
Requires GTP

Question 15

Describe the rate limiting step of gluconeogenesis.

Answer 15

FBPase-1 converts F1,6bisP into F6P

FBPase-1 inhibited by F2,6bisP

Question 16

How does the I/G ratio affect the rate limiting steps of glycolysis and gluconeogenesis.

Answer 16

For both reactions, the rate limiting step is between F6P and F1,6bisP.
The enzymes used are PFK-1 and FBPase-1.
Both are allosterically affected by F2,6bisP.
Levels of F2,6bisP are controlled by the I/G ratio. When high, PKF-2 is active and dephosphorylated and this activates PKF-1 and inhibits FBPase-1. When I/G is low, PFK-2 is phosphorylated and inactivated. PFK-1 is then inhibited and FBPase-1 is activated.

Question 17

Describe the last regulatory step of gluconeogenesis.

Answer 17

G6P is converted to glucose for export from the liver and kidneys by G6Pase.

Question 18

What gluconeogetic precursors also regulate gluconeogenesis?

Answer 18

Availability of amino acids, glycerol, and lactate all influence the rate of glucose synthesis in the liver.

Question 19

What is the Cori cycle?

Answer 19

It links the activity of the liver with activity in the muscles or RBC’s. The liver produces glucose through gluconeogenesis and the muscles or RBC’s use the glucose anaerobically to produce lactate which is shipped back to the liver as a precursor for gluconeogenesis.

Question 20

Explain protein sparing effect and the processes and molecules involved.

Answer 20

It all starts with beta-oxidation.
Beta-Ox produces A-CoA, NADH, FADH2
A-CoA is used for ketogenesis
NADH, FADH2 make ATP and slow the TCA cycle
Slow TCA means that OAA is used for Gluconeogenesis and not put through the TCA for the energy of the cell.

Question 21

What are the protein sparing molecules in the fed, and fasting states?

Answer 21

Fed: dietary carbs
Short fast: glycogen
Long fast: ketones