Gluconeogenesis

Question 1

Why is it important

Answer 1

Formation of glucose from non carb precursors

In order to maintain blodd glucose levels within a very narrow range…since we can only store so much glycogen

Question 2

How does it bypass the irreversible steps of glycolysis (3)

Answer 2

4 new enzymes

Question 3

Pyruvate carboxylase

Answer 3

First of 2 reactions that reverses the glycolytic PK reaction

Conversts pyruvate to OAA by carboylation

Uses ATP X2

Requires BIOTIN as a cofactor

Question 4

phophoenolpyruvate carboxykinase (PEPCK)

Answer 4

OAA—>PEP

Needs GTP X2

Removes CO2

Question 5

Fructose 1,6-bisphosphatase-1 (FBPase-1)

Answer 5

F16BP —> F6P

Question 6

Glucose-6-phosphatase

Answer 6

G6P —> Glucose

Question 7

Organs that can do gluconeogenesis

Answer 7

Liver

Kindeey

Intesetinal epithelium

Adipose (hasd 2/4 enzymes)

Question 8

Why can muscle not do gluconeogeneis

Answer 8

Does nto have G6Ptase

Question 9

Gluconeogenesis enzymes within the cell

Answer 9

Pyruvate carboxylase = mitochondria

PEPCK = mitochondria and cytosol

FBPase-1 = cytosol (regulated within cytosol)

G6Ptase = ER (separates it from hexokinase activity)

Question 10

Net reaction for gluconeogenesis

Answer 10

2 pyruvate +4ATP +2NADH+ 2H + 2water —>

Glucose + 4ADP + 2 GDP + 6Pi + 2NAD+

Question 11

Steps that use energy

Answer 11

2ATP Pyruvate carboxylase

2GTP PEPCK reaction

2ATP reverse of step 7 (phosphoglycerate kinase reactino)

2NADH glyceradlehyde-3-phosphate dehydrogenase…reverse of step 6

Question 12

Primary amino acid precursor

Answer 12

Alanine

Converted in one step to pyruvate

A keto group is converted to an amino group via a transaminase reaction

Question 13

Lactate

Answer 13

Converted to pyruvate

Question 14

Glycerol

Answer 14

Precursor

Released by hydrolysis of TGs in adipose tissue

Can enter gluconeo pathway after a few reactions that convery glycerol to DHAP

Question 15

Why can’t Acetyl CoA enter gluco?

Answer 15

Produced via

• pyruvate hydrogenase complex
• beta-oxidation of FAs
• breakdown of ketogenic amino acids

Can be used to make ketone bodies but not glucose due to stoichiometric considerations

Means that FAs cannot directly feed into glucose production, but TGs can

Question 16

Pyruvate carboxylase allosteric activation

Answer 16

Acetyl-CoA is a marker of the well fed state meaning the cell has sufficient ATP for gluconeogenesis

It allosterically activates this enzyme

Question 17

High insulin:glucagon stimulates transcription of which irreversible glycolytic enzymes

Answer 17

Glucokinase

PFK-1

PK

Question 18

High glucagon:insulin —> increase tcx in which enzymes

Answer 18

PEPCK, F1,6BP, G6Ptase

Question 19

Glyceroneogenesis

Answer 19

Glycerol3-phosphate from pyruvate

Needed to as a backbone for building TGs to store as fuel

Occurs in the liver and adipose cells

Question 20

Well feed verus fasting for lipid storage and mobilization

Answer 20

Well-fed

FFAs circulatin in blood taken up by haptoctyes or adipocytes —> thes FFAs then become re-esterfied to the glycerol-3-phosphate backbone, that has been generated from pyruvate through glyceroneogensis —> produce TGs to store fat

Fasting state

High glucagon:insulin —> adiposse hydrolyze the ester bonds between glycerol and FAs in stored TGs —> release FFAs and glycerol into blood —> FFAs taken up by muscle and oxidized for energy, glycerol taken up by the liver for gluconeogenesis

Question 21

Type II diabetes connection

Answer 21

Insensitivity to insulin

Higher serum FFAs can reduce insulin sensitivity —> leading to peripheral tissues becoming more resistant to insulin signaling

Then blood glucose levels could rise with high FFAs levels —> Type II

Question 22

Drug rosiglitazone

Answer 22

Therapy to control diabetes

Induces PEPCK —> increase glyceroneogenesis —> decrease in FFA release from adipose tissue