Regulation of glycolysis and glucoenogenesis

Question 1

When glycolysis and glucoenogenesis are stimulated

Answer 1

Glycolysis- when AMP is high and ATP is low

Glucoenogenesis- when AMP is low and High ATP

Question 2

What hormones regulate expression function of glycolytic enzymes

Answer 2

Glucagon, epinephrine and insulin

Question 3

4 different types of hexokinases

Answer 3

1,2,3,4

Question 4

Characteristics of hexokinase I and II

Answer 4

• Predominant in muscle
• High affinity for glucose (activity reaches maximum quickly)
• Allosterically inhibited by G-6-P ( negative feedback by the product)

Question 5

The other name for hexokinase IV

Answer 5

Glucokinase

Question 6

Characteristics of hexokinase IV

Answer 6

• Predominant in liver
• Lower affinity for glucose ( it will reach its maximum activity when the concentration is very high)
• Not inhibited by G-6-P
• Glucose escapes glycolysis at low concentration
• Inhibited by a regulatory protein (liver specific, GKRP)

Question 7

What is GKRP

Answer 7

Glucokinase regulatory protein
can take the enzyme from the cytoplasm to the nucleus, thus inhibiting the reaction
It can also drive it back, when glucose concentrations are high

Question 8

What stimulates /inhibits GKRP

Answer 8

Stimulates- glucose

Inhibits- fructose 6-phosphate

Question 9

Major cites of glycolysis and gluconeogenesis

Answer 9

Glycolysis- any cell

A few can do glycoenogenesis- kidney, intestinal epithelium

Question 10

What is stimulated at low and high glucose concentrations

Answer 10

High blood glucose- Hexokinase IV

Low blood glucose- Glu-6-phosphatase

Question 11

What stimulates and inhibits PFK-1

Answer 11

High ATP allosterically inhibits PFK-1
High AMP or ADP relieve ATP-inhibition
High citarte increases ATP-inhibition

Question 12

What inhibits FBPase-1

Answer 12

High AMP allosterically inhibits FBPase-1

Question 13

What is the specific molecule that regulates both PFK-1 and FBPase-1 in the liver

Answer 13

Fructose 2,6-biphosphate (F26BP). It acts as allosteric activator of PFK-1 and inhibitor of FBPase-1

Question 14

What synthesize F26BP

Answer 14

PFK-2/FBPase-2. It is the same enzye that has both functions. PFK-2 converts fructose 6-phosphate to Fructose 2,6-biphosphate with the use of ATP. And FBPase-2 converts F26BP to fructose 6-phosphate

Question 15

What is the difference between PFK-2 and FBPase-2 and PFK-1 and FBPase-1 (genes)

Answer 15

PFK-2/FBPase-2 expressed from single gene (PFKFB1)

PFK-1 and FBPase-1 are encoded by two genes, PFKM and FBP1

Question 16

If the same gene regulates expression of both enzymes how it decided which will perform what function

Answer 16

Posttranslational modification. If it dephosphorylated->PFK-2 activity
In the phosphorylated state FBPase-2 activity

Question 17

What happens when PFK-2 is phosphorylated

Answer 17

More synthesize of F26BP-> stimulation of glycolysis->inhibition of glucoenogenesis

Question 18

What happens when FBPase-2 activity is higher that PFK-2

Answer 18

Lower concentration of F26BP. it is converted to fructose-6 phosphate
Inhibition of glycolysis, stimulation of glucoenogenesis

Question 19

Who removes and who phosphorylates PFK-2 and FBPase-2

Answer 19

Insulin stimulates-> phospho-protein phosphotase->PFK-2. Xylulose 5-phosphate stimulates dephosphorylation.( meaning a lot of pentose phosphate pathway happening)

Glucagon receptor–>GPCR->cAMP-dependent protein kinase(pka)->FBPase-2 activity

Question 20

What is the pyruvate kinase regulation in all cells, including liver

Answer 20

Negative feedback by the product or positive by the substrate
ATP,acetyl-CoA, long chain FA, Alanine inhibit pyruvate kinase

F16BP activates pyruvate kinase

Question 21

What is the pyruvate kinase regulation in liver

Answer 21

Glucagon activates PKA that phosphorylates pyruvate kinase, inactivating it.

Then protein phosphatases can remove phosphate and make it active

Question 22

Muscle isoform of pyruvate kinase is not regulated by ___, because

Answer 22

Is not regulated by PKA phosphorylation, because they do not have glucagon receptor

Question 23

Fate of pyruvate in the liver

Answer 23

Pyruvate conversion to acetyl-coA is inhibited by acetyl-CoA
And acetyl-CoA activates pyruvate carboxidase driving glucoenogenesis

Question 24

When do we have high concentration of acetyl CoA

Answer 24

When liver has sufficient FA for beta-oxidation

Question 25

Insulin increases expression of and inhibits

Answer 25

Increasing- glycolytic enzymes

Decreasing- enzymes involved in glucoenogenesis

Question 26

Regulation of transcription by ChREBP

Answer 26

It is a carbohydrate response element binding protein (TF)

When glucose gets into the cell, during pentose phosphate pathway xylulose 5-phosphate is produced. It stimulates protein phosphatase that removes phosphate group from ChREBP. ChREBP is dephosphorylated in two steps. The first step is dephosphorylation of serine residue and the second is dephosphorylation of threonine.
ChREBP goes into the nucleus, where it bonds to ChoRE(carbohydrate response element). This binding activates FA synthesis and Glycolysis
So when we eat a lot of sugar-> increased glycolysis and FA synthesize

Question 27

The second mechanism that regulate glucoenogenesis

Answer 27

FOXO1 represses enzymes for glycolysis. When PKB is activated by insulin, FOXO1 is phosphorylated it is ubiquitinated and destroyed.
No insulin-> no phosphorylation-> active FOXO1 binds to the gene-> transcription of PEP carboxykinase and Glucose 6-phosphatase and inhibits the enzymes of glycolysis and FA sythesis