Kerry Loomes-3 Flashcards
How do the hormonal effects on glycolysis differ between liver and muscle?
In muscle glycolysis is central to producing energy so there is very little gluconeogenesis while in the liver stores glucose as glycogen and triglyceride when in the fed state but also undergoes glycogenolysis and gluconeogenesis to provide glucose for other tissues despite not consuming it itself
What are the two forms of pyruvate kinase and what is their purpose?
There is an M form which is in muscle and an L from which is in liver these two forms exist as they have different regulatory mechanisms so they can better suit the needs of the tissue
How can glucagon and epinephrine drive gluconeogenesis in the liver?
They decrease the concentration of fructose-2,6, bisphosphate resulting in a loss of stimulation of phosphofructokinase (which drives glycolysis) and removing an inhibitor of fructose-1,6-bisphosphatase which is used to overcome the 2nd irreversible step of glycolysis
How is fructose-2,6-bisphosphate produced?
The bifunctional enzyme phosphofructokinase2/fructose-2,6-phosphatase
The kinase generates fructose 2,6 phosphate while the phosphatase can remove this phosphate to generate fructose-6P
How is the bifunctional phosphofructokinase2/fructose-2,6-phosphatase enzyme regulated?
There is also a regulatory domain, phosphorylation will switch the kinase off and the phosphatase on
There are 5 highly related isoforms with an L and M variant to provide for the separate needs of the liver and muscle
How do glucagon and epinephrine reduced the concentration of fructose-2,6-bisphosphate in the liver?
Activation of protein kinase A which phosphorylates PFK-2 to inactivate it reducing the fructose-2,6-bisphosphate concentration and driving gluconeogenesis
How is pyruvate kinase regulated in the liver?
The liver isoform is inhibited by ATP, Alanine, acetyl-coA as well as inactivated by phosphorylation
It is stimulated by fructose-1,6-bisphosphate
insulin can reactivate this enzyme via protein phosphatase 2A
Why is there a difference in the way in which skeletal muscle and liver respond to epinephrine?
The bifunctional enzyme in muscle is not regulated by phosphorylation and therefore only sensitive to levels of fructose-6P which increases activity so there is more fructose-2,6-bisphosphate and thus greater drive down the glycolytic pathway via stimulation of phosphofructokinase
How is pyruvate kinase regulated in muscle?
Not by phosphorylation as in the liver, it is also not inhibited by alanine so the amino acid can still be transported to the liver
Instead it is regulated through allosteric stimualtion from fructose-1,6 bisphosphate
Why is cardiac muscle a special case?
Activated protein kinase A increases levels of fructose-2,6-bisphosphate and drives glycolysis
Why is AMP positive regulator of phosphofructokinase and fructokinase?
Acts as a signal for the low energy state
Has a magnification effect as there are only small concentrations in the cell so a small change in amount leads to a large change in percentage leading to tighter control
How is AMP produced?
Adenylate kinase uses 2ADP molecules to make 1ATP and one AMP
