Fasting State
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66 Terms
What is the rate limiting enzyme of gluconeogenesis?
FBPase 1
What allosterically inhibits FBPase 1?
Fructose 2 6 bisphosphate
What happens to fructose 2 6 bisphosphate during fasting?
It is cleared by activated FBPase 2
Why does FBPase 1 become more active during fasting?
Because fructose 2 6 bisphosphate inhibition is reduced
What happens to PFK 1 activation during fasting?
It stops because fructose 2 6 bisphosphate is cleared
What happens to the bifunctional enzyme PFK 2 FBPase 2 during fasting?
It becomes phosphorylated
Why is pyruvate kinase inhibited in the liver during fasting?
To prevent glycolysis and preserve carbon for gluconeogenesis
Is pyruvate kinase regulated the same way in muscle?
No
Why is muscle pyruvate kinase not inhibited during fasting?
Muscle does not express the glucagon receptor
What pathway regulates pyruvate kinase in the liver during fasting?
Glucagon GPCR to cAMP to protein kinase A
What is the key enzyme of the HMP shunt?
Glucose 6 phosphate dehydrogenase
What controls the rate of the HMP shunt?
NADP plus concentration
Is G6PD regulated by covalent modification?
No
What enzyme breaks down glycogen during fasting?
Glycogen phosphorylase
What inhibits glycogen phosphorylase?
Glucose 6 phosphate
How is glycogen phosphorylase activated during fasting?
By phosphorylation from phosphorylase kinase
How is phosphorylase kinase activated?
By phosphorylation
Which enzyme controls both glycogen phosphorylase and its kinase?
Protein kinase A
What activates isocitrate dehydrogenase in the TCA cycle?
ADP and calcium
What inhibits isocitrate dehydrogenase?
ATP and NADH
What activates alpha ketoglutarate dehydrogenase complex?
Calcium
What inhibits alpha ketoglutarate dehydrogenase complex?
NADH and succinyl CoA
How many enzymes are in the pyruvate dehydrogenase complex?
Three
How many coenzymes are used in the PDH complex?
Five
What activates the PDH complex?
Pyruvate and dephosphorylation
What inhibits the PDH complex?
Acetyl CoA ATP and NADH
What regulates the PDH complex via covalent modification?
Phosphorylation inhibits and dephosphorylation activates
Why is PDH complex inhibited during fasting?
Because fatty acid oxidation increases acetyl CoA
Which metabolic fuel rises during fasting?
Fatty acids and ketone bodies
What does the liver use as energy to power gluconeogenesis and the urea cycle?
Fatty acids
What does increased acetyl CoA activate in the liver?
Pyruvate carboxylase
What reaction does pyruvate carboxylase catalyze?
Conversion of pyruvate to oxaloacetate
What cofactor does pyruvate carboxylase require?
Biotin
Why is pyruvate converted to OAA during fasting?
To support gluconeogenesis and avoid wasteful acetyl CoA production
Why is PDH complex downregulated when pyruvate carboxylase is activated?
To divert pyruvate to oxaloacetate instead of acetyl CoA
Why must gluconeogenesis occur in the fasting state?
To maintain blood glucose levels for glucose dependent tissues
What are the eight reversible enzymes shared by glycolysis and gluconeogenesis?
They are used in both directions depending on metabolic needs
What enzyme clears fructose 2 6 bisphosphate during fasting?
FBPase 2
Why is fructose 2 6 bisphosphate clearance important during fasting?
It removes inhibition from FBPase 1 and stops glycolysis
Why does the liver increase gluconeogenesis during fasting?
To maintain blood glucose levels for the brain and red blood cells
Why does fructose 2 6 bisphosphate decrease during fasting?
Because glucagon signaling activates FBPase 2
Why is fructose 2 6 bisphosphate important in metabolic regulation?
It stimulates glycolysis and inhibits gluconeogenesis
Why does the body reduce fructose 2 6 bisphosphate during fasting?
To inhibit glycolysis and activate gluconeogenesis
What is the benefit of phosphorylating pyruvate kinase in the liver during fasting?
It stops pyruvate formation and conserves PEP for gluconeogenesis
Why is muscle not affected by glucagon?
Because muscle cells lack the gene for the glucagon receptor
Why must muscle continue glycolysis during fasting?
Muscle requires constant ATP to function
Why is NADPH not a major regulatory factor during fasting?
Because anabolic processes like lipid synthesis are suppressed
Why is glucose 6 phosphate an inhibitor of glycogen phosphorylase?
To prevent unnecessary glycogen breakdown when glucose is present
What is the role of protein kinase A in fasting state metabolism?
It phosphorylates key enzymes to shift metabolism from storage to release
Why is calcium an important activator in the TCA cycle during fasting?
It indicates muscle contraction or increased energy demand
How does acetyl CoA affect the fate of pyruvate during fasting?
It inhibits PDH and activates pyruvate carboxylase to favor OAA production
What would happen if PDH remained active during fasting?
Pyruvate would be wasted on acetyl CoA instead of being used for glucose production
What signals high fatty acid oxidation in the liver during fasting?
Increased levels of acetyl CoA
What is the significance of activating pyruvate carboxylase in fasting?
It allows gluconeogenesis to continue using pyruvate
Why is biotin essential for fasting metabolism?
It is required for pyruvate carboxylase to produce oxaloacetate
Why is oxaloacetate important in fasting?
It is a key intermediate in gluconeogenesis and the TCA cycle
How does fasting affect the TCA cycle in the liver?
It slows as OAA is pulled away for gluconeogenesis
What is the relationship between beta oxidation and PDH regulation?
Beta oxidation increases acetyl CoA which inhibits PDH
Why is the HMP shunt minimally active during fasting?
Because NADPH demand is low without anabolic activity
Why must reversible glycolytic enzymes remain active during fasting?
To allow shared use for both glycolysis and gluconeogenesis
How does the liver prioritize glucose output during fasting?
By inhibiting glycolysis and activating gluconeogenesis
Why does the liver stop using glucose during fasting?
To conserve glucose for tissues like brain and red blood cells
What would happen if gluconeogenesis failed during fasting?
Blood glucose would drop leading to hypoglycemia
Why is enzyme regulation during fasting often achieved by phosphorylation?
It allows rapid hormone driven control of key enzymes
Why does the liver use fatty acid oxidation instead of glucose during fasting?
To spare glucose for export and support gluconeogenesis
How is metabolic fuel use partitioned during fasting?
Liver uses fats muscle uses fats and brain uses glucose and ketones
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