Regulation of glycolysis and glucoenogenesis Flashcards
When glycolysis and glucoenogenesis are stimulated
Glycolysis- when AMP is high and ATP is low
Glucoenogenesis- when AMP is low and High ATP
What hormones regulate expression function of glycolytic enzymes
Glucagon, epinephrine and insulin
4 different types of hexokinases
1,2,3,4
Characteristics of hexokinase I and II
- Predominant in muscle
- High affinity for glucose (activity reaches maximum quickly)
- Allosterically inhibited by G-6-P ( negative feedback by the product)
The other name for hexokinase IV
Glucokinase
Characteristics of hexokinase IV
- 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)
What is GKRP
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
What stimulates /inhibits GKRP
Stimulates- glucose
Inhibits- fructose 6-phosphate
Major cites of glycolysis and gluconeogenesis
Glycolysis- any cell
A few can do glycoenogenesis- kidney, intestinal epithelium
What is stimulated at low and high glucose concentrations
High blood glucose- Hexokinase IV
Low blood glucose- Glu-6-phosphatase
What stimulates and inhibits PFK-1
High ATP allosterically inhibits PFK-1
High AMP or ADP relieve ATP-inhibition
High citarte increases ATP-inhibition
What inhibits FBPase-1
High AMP allosterically inhibits FBPase-1
What is the specific molecule that regulates both PFK-1 and FBPase-1 in the liver
Fructose 2,6-biphosphate (F26BP). It acts as allosteric activator of PFK-1 and inhibitor of FBPase-1
What synthesize F26BP
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
What is the difference between PFK-2 and FBPase-2 and PFK-1 and FBPase-1 (genes)
PFK-2/FBPase-2 expressed from single gene (PFKFB1)
PFK-1 and FBPase-1 are encoded by two genes, PFKM and FBP1
If the same gene regulates expression of both enzymes how it decided which will perform what function
Posttranslational modification. If it dephosphorylated->PFK-2 activity
In the phosphorylated state FBPase-2 activity
What happens when PFK-2 is phosphorylated
More synthesize of F26BP-> stimulation of glycolysis->inhibition of glucoenogenesis
What happens when FBPase-2 activity is higher that PFK-2
Lower concentration of F26BP. it is converted to fructose-6 phosphate
Inhibition of glycolysis, stimulation of glucoenogenesis
Who removes and who phosphorylates PFK-2 and FBPase-2
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
What is the pyruvate kinase regulation in all cells, including liver
Negative feedback by the product or positive by the substrate
ATP,acetyl-CoA, long chain FA, Alanine inhibit pyruvate kinase
F16BP activates pyruvate kinase
What is the pyruvate kinase regulation in liver
Glucagon activates PKA that phosphorylates pyruvate kinase, inactivating it.
Then protein phosphatases can remove phosphate and make it active
Muscle isoform of pyruvate kinase is not regulated by ___, because
Is not regulated by PKA phosphorylation, because they do not have glucagon receptor
Fate of pyruvate in the liver
Pyruvate conversion to acetyl-coA is inhibited by acetyl-CoA
And acetyl-CoA activates pyruvate carboxidase driving glucoenogenesis
When do we have high concentration of acetyl CoA
When liver has sufficient FA for beta-oxidation
Insulin increases expression of and inhibits
Increasing- glycolytic enzymes
Decreasing- enzymes involved in glucoenogenesis
Regulation of transcription by ChREBP
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
The second mechanism that regulate glucoenogenesis
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
