Review: Adenylate Kinase: an "Important Metabolic Regulator"
ATP + AMP <---> 2 ADP
During intense exercise: large conversion of ATP to ADP with the muscle attempting to phosphorylate ADP back to ATP, this increase in ADP pushes the reaction to the left (mass action effect)
i.e. a 20% decrease in ATP leads to an almost 3-fold increase in ADP and ultimately a 1,400% increase in AMP
The increase in AMP is what's important here......
Because AMP is an allosteric regulator that signals a low energy state in cells --------->
rise in AMP increases metabolism through pathways to restore energy (i.e. glycolysis, citric acid cycle etc.).
Hexokinase / Glucokinase: both irreversible
Glucose + ATP ----> Glucose-6-phosphate + ADP
Catalyzes the phosphorylation of hexoses in general and is found in all cells that metabolize glucose.
Has a low Km (high affinity, strong binding) so that it is active even at low glucose concentrations.
Feedback inhibited by its product glucose-6-phosphate. Prevents build-up of glycolytic intermediates and the unnecessary hydrolysis of ATP.
Glucose specific, found in liver only. Synthesis induced by insulin.
Has a high Km (low affinity,weak binding) to ensure an appropriate response to elevation of glucose from the diet, provides kinetic control.
High Vmax (rapid phosphorylation of glucose).
Phosphofructokinase-1 (PFK-1): glycolysis, irreversible
Fructose-6-phosphate + ATP ------> Fructose-1,6-bisphosphate + ADP
Rate-Limiting, Major Regulated Step.
The concentration of AMP increases when energy is low. Excess phosphate also signals low energy (via increase in ATP use). -------> glycolysis must increase to meet energy demands by metabolizing glucose.
Allosterically (+) AMP, F-2,6-bisP, phosphate
Allosterically (-) ATP
Fructose 1,6-bisphosphatase: gluconeogenesis, irreversible
Fructose-1,6-bisphosphate ------> Fructose-6-phosphate
Can form a futile cycle with phosphofructokinase-1 (PFK-1)
The two enzymes are reciprocally regulated or ATP would be lost without energy conservation. Prevents futile cycling (like using a stationary bike).
Allosterically (+) citrate (high flux of carbons from glucose to the citric acid cycle requiring decreased glycolysis and increased gluconeogenesis).
Allosterically (-) AMP, Fructose-2,6-bisP
Formation: Phosphofructokinase-2 (PFK-2)
Breakdown: Fructose-2,6 bisphosphatase (FBPase-2)
PFK-2 is NOT a glycolytic enzyme.
It does use some Fructose-6-P from the pathway, but Fructose-2,6-bisP is strictly an allosteric regulator of PFK-1.
High Glucose: dephosphorylated ----> PFK-2 active ----> Fructose-2,6-bisP produced ----> (+) glycolysis, (-) gluconeognesis.
Low Glucose: phosphorylation ----> FBPase-2 ----> Fructose-2,6-bisP removed ----> (+) gluconeogenesis, glycolysis (-)
Pyruvate Kinase: "Substrate Level Phosphorylation"
Phosphoenolpyruvate + ADP -------> Pyruvate + ATP
Irreversible, Highly Regulated.
Produces 2 ATP.
(-) Citrate (high flux of carbons from glucose to the citric acid cycle requiring decreased glycolysis and increased gluconeogenesis)
ATP. Both prevent the build-up of phosphorylated intermediates.
Alanine, a major precursor for gluconeogensis
(+) Fructose-1,6-bisP, PEP (ensure that intermediates between are kept at a minimal conc.)
Mitochondrial enzyme, requires biotin as a prosthetic group to carry CO2.
Activated (+): by acetyl CoA (diverts some of the Pyruvate) in concert with the inhibition (-) of Pyruvate DH.
© Dr. Noel Sturm 2019
Disclaimer: The views and opinions expressed on unofficial pages of California State University, Dominguez Hills faculty, staff or students are strictly those of the page authors. The content of these pages has not been reviewed or approved by California State University, Dominguez Hills.