Gluconeogenesis (Deevska)

Question 1

What is Gluconeogenesis?

Answer 1

A metabolic pathway that results in the generation of glucose from non-carb precursors.

Question 2

What human tissues does GNG occur?

Answer 2

Liver- predominantly ~90%

Kidney Cortex ~10%

Question 3

Where in the cell does GNG occur?

Answer 3

Mitochondrial matrix- step 1.
Cytosol- reversible steps of glycolysis
ER- last step to produce glucose

Question 4

_______ is released during hydrolysis of TAGs in adipocytes and is delivered by the blood to the liver

Answer 4

Glycerol

Question 5

4 main substrates from GNG?

Answer 5

Glycerol, Amino acids, and Lactate to form glucose

Question 6

Main amino Acid used in GNG.

Answer 6

ALA is major amino acid… Most converted to intermediates in TCA that can yield Oxaloacetate

Question 7

What can be converted back into pyruvate in the liver by lactate dehydrogenase?

Answer 7

Lactate

Question 8

What is the Cori Cycle?

Answer 8

Glucose converted to lactate under anaerobic conditions, excreted to blood plasma and sent to the liver to be converted back to glucose and released into circulation.

Question 9

True/ False Acetyl CoA cannot be converted into pyruvate in humans.

Answer 9

True. It is an irreversible step in glycolysis because PDH is irreversible and NO enzyme for reverse rxn.

Question 10

_________ oxidation provides the liver with the energy needed to perform GNG

Answer 10

Fatty acid

Question 11

True/False. Fatty acids cannot serve as a substrate for GNG.

Answer 11

True. Cannot be used to make glucose… just energy for GNG.

Question 12

What type of pathway is GNG?

Answer 12

Anabolic, needs energy/ building complex molecules.

Question 13

What type of pathway is Glycolsis?

Answer 13

Catabolic, making energy to drive other chemical rxns.f

Question 14

How many reactions are involved in GNG? How many reversible and how many irreversible?

Answer 14

11 steps
7 reversible (use same enzymes as glycolysis)
3 irreversible

Question 15

Know 4 Reactions unique to gluconeogenesis

Answer 15

1. Carboxylation of pyruvate to OAA
2. Decarboxylation of cytosolic OAA to PEP
3. Dephosphorylation of fructose 1,6 bisphosphate to F-6-P
4. Dephosphorylation of glucose 6-Phosphate to Glucose

Question 16

What enzymes are involved in step 1: carboxylation of pyruvate to OAA?

Answer 16

Pyruvate carboxylase, uses biotin as coenzyme.
-allosterically activated by acetyl CoA
Malate dehydrogenase
PEP carboxylase

Question 17

What enzymes and specifics are in step 2: Decarboxylation of cytosolic OAA?

Answer 17

irreversible, driven by GTP hydrolysis

PEP-carboxykinase (PEPCK)

Question 18

What pairing makes GNG energetically favorable?

Answer 18

Pairing carboxylation with de-carboxylation conserves energy.

Question 19

What enzymes and specifics are in step 3: Dephosphorylation of fructose 1,6-bis-P?

Answer 19

Hydrolysis rxn, bypasses PFK-1 rxn, important site for regulation.
Enzymes: Fructose 1,6 bisphosphatase
Inhibitors: AMP and allosterically by fructose 2,6 bisphosphate
Activators: high ATP, low AMP