Regulation of glycolysis and gluconeogenesis Flashcards
The Pasteur Effect
Anaerobic yeast are exposed to oxygen and their rate of glucose utilization decreases greatly and they become more efficient because aerobic glycolysis produces 30-32 ATP per 1 glucose whereas anaerobic glycolysis produces 2 ATP and 2NADH per 1 glucose
What is the important control point of anaerobic glycolysis
Intracellular levels of glycolytic intermediates after oxygenation are pointing towards the conversion of F6P to F1,6BP as an important control point (PFK). (add oxygen at reaction 3 = less glucose is used)
Glycolysis and gluconeogenesis are controlled where?
1) Reaciton 1
2) Reaction 3
3) Reaction 10
Regulation of glycolysis and gluconeogenesis is mostly achieved by
allosteric regulators
Allosteric Control (Allostery)
Modulator binds to regulatory site to either make enzyme more or less efficient (can be positive or negative effects)
In image:
Green Line = more efficient
Red line = less efficient
Overall regulation map of glycolysis and gluconeogenesis
Reaction 1 at top of image
Reaction 3 in the middle
Reaction 10 at bottom
Regulation of glycolysis reaction 1 is controlled by (2 things)
1) Allosteric control of hexokinase
2) Inhibited by glucose-6-phosphatase
Is reaction 1 regulation true for all organs
No, muscle and liver will have different regulation
Characteristics of Reaction 1 regulation by Hexokinase I (possibly 1-3?)
1) Hexokinase I (muscles and most others tissues)
2) Inhibited by glucose-6-phosphate
Characteristics of Reaction 1 regulation by Hexokinase IV
1) Not inhibited by glucose-6-phosphate
2) Because glucokinase is NOT inhibited by G6P, it can keep producing G6P at [ ] at which hexokinase I would have long been inhibited. This G6P can be used in other pathways, such as glycogen metabolism and pentose phosphate pathway.
Compare and contrast the vmax of hexokinase I vs hexokinase IV
1) Hexokinase I is always at Vmax so will produce maximum, but there is feedback to stop its use
2) Hexokinase IV is regulated on blood glucose concentrations and does not reach vmax easily
Explain the regulation system of hexokinase IV
- GLUT2, establishes an equilibrium between the concentration of glucose in the blood and the hepatocytes (liver cells).
2.When the concentration of glucose increases, the increasing concentration in glucose will act as an allosteric inhibitor of the glucokinase (hexokinase IV) regulatory protein(GKRP).
- GKRP sequesters hexokinase IV in the nucleus
- Under high glucose conditions, hexokinase IV is released to the cytosol.
low glucose = hexokinase IV in the liver will not work
high glucose = hexokinase IV in the liver will work
Explain this image
1) When high levels of blood glucose, it moves into the cytosol and is converted by hexokinase IV (which moves into the cytosol) to G6P
- When low levels of blood glucose, means less glucose in the cytosol, fructose 6-phosphate acts as an allosteric activator of GKRP, increasing its binding to hexokinase IV so the hexokinase IV stays bound to the regulatory protein in the nucleus
**High glucose sequesters hexokinase IV into the cytosol
**Low glucose = GKRP sequesters hexokinase IV in the nucleus
Regulation of Reaction 11 (reaction 1 glycolysis) of gluconeogenesis
Conversion of glucose-6-phosphate into glucose by the glucose-6-phosphatase will be promoted at high [ ] of G6P.
Explain the regulation in terms of Vmax for reaction 11 of gluconeogenesis
1) The glucose-6-phosphatase KM (2-3 mM) is higher than the intracellular concentration of G6P (0.05-0.1 mM).
2) Therefore, the activity of the enzyme will increase in relation to the increase in G6P concentration and G6P increased concentration will push the enzyme to Vmax and increase the activity