Describe the regulation of hexokinase/glucokinase, phosphofructokinase-1 (PFK-1)
ID: 86494 • Letter: D
Question
Describe the regulation of hexokinase/glucokinase, phosphofructokinase-1 (PFK-1), and pyruvate kinase in glycolysis
23: Compare and contrast the mechanisms for regulating glycolysis including allostery, hormonal regulation and covalent modification
24: Describe the regulation of hexokinase/glucokinase, phosphofructokinase-1 (PFK-1), and pyruvate kinase in glycolysis
24: Describe feed-forward activation (Module 1)
25: Provide examples of each of the following major classes of receptors and compare and contrast their mechanism of signaling and termination: receptor tyrosine kinases, serine/threonine linked receptors, G-Protein coupled receptors (heptahelical receptors), cytoplasmic/nuclear receptors and ion channel receptors
Explanation / Answer
The hexokinase is an allosteric enzyme which is inhibited by glucose-6-phosphate. Glucokinase is not inhibited by product as it is highly specific to D-glucose and has a higher Km for it. Glucokinase is an inducible enzyme and is regulated by insulin.
Phosphofructokinase-1 is regulated by ATP which acts as an inhibitor. When the level of ATP is high, the Km for fructose-6- phosphate is increased resulting in turning off of glycolysis. AMP, on the other hand, reverses the ATP’s inhibitory action. Phosphofructokinase-1 is also inhibited by citrate. Citrate inhibits the enzyme by elevating the inhibitory effect of ATP. Phosphofructokinase-1 is activated by D-fructose-2,6-bisphosphate by increasing the affinity for the substrate( fructose-6-phoshate) and decreasing the inhibitory effect of ATP. This enzyme is also controlled by pH. Decrease in pH causes inhibition which prevents excessive lactic acid formation and a drop in blood pH.
Pyruvate Kinase has allosteric sites for a number of effectors. It is activated by AMP and fructose-1,6-bisphosphate and inhibition is caused by ATP, acetyl-Co A and alanine. It is also regulated by covalent modification. Hormones like glucagon activate a c-AMP dependent protein kinase. The phosphorylated pyruvate kinase is strongly inhibited by ATP and alanine.
Tyrosine Kinases (phosphorylation): insulin receptor and jak-STAT
Serine- threonine kinase: TGF beta
G-protein coupled receptor(GPCR): glucagon and epinephrine receptor
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