Enzyme regulation

What molecules can decrease hexokinase activity?

Glucose-6-phosphate, acts as a non-competitive inhibitor

How does the conformation of hexokinase change for catalysis?

Binding of glucose leads to a conformational change, traps glucose into the enzyme ensuring a reaction with ATP

How is glucokinase controlled?

Not inhibited by glucose-6-phosphate, only acts in high glucose concentrations due to low affinity

How can pyruvate kinase activity be increased by allosteric control?

Fructose-1, 6-bisphosphate increases activity

How can pyruvate kinase activity be decreased by allosteric control?

ATP and alanine decrease activity.
Phosphorylation of PK is less active

How does fructose-1, 6-bisphosphate increase pyruvate kinase activity?

Increases binding affinity for phosphoenolpyruvate.
Stabilises tetramer formation

How can phosphofructokinase 1 activity be increased?

By fructose-2, 6-bisphosphate and AMP

How can phosphofructokinase 1 activity be decreased?

BY ATP and citrate

How do ATP and AMP affect phosphofructokinase 1 activity?

ATP reduces affinity for fructose-6-phosphate.
AMP reverses ATP inhibitory effect

How are the subunits of phosphofructokinase 2 regulated?

Phosphofructokinase and fructose bisphosphatase 2 activity.
Phosphorylation increases FBPase activity.
Phosphorylation due to PKA

How is the PDC regulated allosterically?

Due to phosphorylation by PDC kinase or dephosphorylation by PDC phosphatase.
Phosphorylated form is less active

What molecules increase PDC phosphatase activity?

Mg2+ and Ca2+

What molecules decrease PDC phosphatase activity?

NADH

What molecules increase PDC kinase activity?

Mg2+, Acetyl-CoA, NADH

What molecules decrease PDC kinase activity?

CoA, pyruvate, ADP

What molecules can decrease citrate synthase activity?

ATP, succinyl CoA.
Succinyl CoA acts as a competitive inhibitor

What molecules increase isocitrate dehydrogenase activity?

ADP

What molecules decrease isocitrate dehydrogenase activity?

ATP, NADH

What molecules decrease α-ketoglutarate activity?

ATP, succinyl CoA, NADH

What increases the action of phosphorylase in muscles?

Adrenaline, electrical stimulation, ATP/AMP levels

What decreases the action of phosphorylase in muscles?

Glucose-6-phosphate

What increases the action of phosphorylase kinase?

PKA, leads to phosphorylation of the β subunit.
Ca2+ binding to δ subunit

What increases the action of fructose-1, 6-bisphosphatase?

Citrate

What decreases the action of fructose-1, 6-bisphosphatase?

Fructose-2, 6-bisphosphate, AMP

What increases the activity of pyruvate carboxylase?

Acetyl CoA

What decreases the activity of phosphoenolpyruvate carboxykinase and pyruvate carboxylase?

ADP

How does insulin regulate glycolytic enzymes?

Promotes expression of phosphofructokinase 1, pyruvate kinase, phosphofructokinase 2

How does glucagon regulate gluconeogenic enzymes?

Increases expression of phosphoenolpyruvate carboxykinase, and fructose-1, 6-bisphosphatase

How can fatty acid synthesis and oxidation be reciprocally regulated?

Malonyl CoA (synthesis) and palmitoyl CoA (oxidation) inhibit each others synthesis

How is β-oxidation regulated rapidly?

Regulated by substrate availability and the rate of lipolysis
Malonyl CoA inhibits carnitine palmitoyltransferase so inhibits LCFA uptake for β-oxidation

How can β-oxidation be regulated in the long term?

Transcriptional control due to peroxisome proliferator activated receptor (PPARα). Upregulates genes involved in β-oxidation

How can acetyl CoA carboxylase be regulated?

Polymerisation due to citrate or depolymerisation due to palmitoyl CoA.
Phosphorylation due to ATP/AMP or glucagon (phosphorylation)/insulin (dephosporylation)

How can acetyl CoA carboxylase be phosphorylated?

Phosphorylated by AMPK, activated by high AMP and low ATP. Causes formation of inactive ACCb form

How can dephosphorylation regulate acetyl CoA carboxylase?

De-phosphorylated by protein phosphatase 2, causes formation of active ACCa.
Dephosphorylation causes activation of fatty acid synthesis

How can cholesterol synthesis be reguilated?

By regulation of HMG CoA reductase

How is bile acid synthesis regulated?

Regulate their own synthesis via nuclear receptors, bind to FXR, LXR, or LRH-1