Gluconeogenesis Flashcards
(20 cards)
Which enzyme converts pyruvate to oxaloacetate during gluconeogenesis?
Pyruvate carboxylase
Pyruvate carboxylase is the first enzyme in gluconeogenesis, converting pyruvate to oxaloacetate in the mitochondria. It requires biotin and is activated by acetyl-CoA.
Which cofactor is essential for the function of pyruvate carboxylase?
Biotin
Biotin acts as a coenzyme for carboxylation reactions like that catalyzed by pyruvate carboxylase.
Which gluconeogenic enzyme is upregulated in response to high levels of acetyl-CoA?
Pyruvate carboxylase
High acetyl-CoA levels signal energy sufficiency, activating pyruvate carboxylase to drive gluconeogenesis.
Why does oxaloacetate need to be converted to malate before leaving the mitochondria?
Oxaloacetate cannot cross the mitochondrial membrane directly
Malate is transported out via the malate shuttle, then reconverted to oxaloacetate in the cytosol.
Which enzyme catalyzes the rate-limiting step of gluconeogenesis?
Fructose-1,6-bisphosphatase
This enzyme bypasses PFK-1 of glycolysis and is inhibited by fructose-2,6-bisphosphate and AMP.
What is the source of the carbons used to make glucose during prolonged fasting?
Amino acids, glycerol, and lactate
These are the three primary non-carbohydrate precursors for gluconeogenesis.
Why does insulin inhibit gluconeogenesis?
It signals a fed state with high glucose
Insulin promotes glucose storage and suppresses new glucose synthesis by downregulating key gluconeogenic enzymes.
What enzyme converts oxaloacetate to phosphoenolpyruvate (PEP)?
Phosphoenolpyruvate carboxykinase (PEPCK)
PEPCK uses GTP to convert oxaloacetate to PEP in the cytosol, a key step in gluconeogenesis.
What vitamin deficiency most likely contributes to impaired gluconeogenesis in a patient with alcoholism?
Biotin or thiamine
Biotin is required for pyruvate carboxylase; thiamine is needed for transketolase and other TCA reactions.
Which enzyme removes the phosphate group from glucose-6-phosphate to produce free glucose?
Glucose-6-phosphatase
This enzyme is present only in the liver and kidney; its absence causes Von Gierke disease.
Why can’t muscle tissue contribute directly to blood glucose via gluconeogenesis?
Lacks glucose-6-phosphatase
Muscle can perform gluconeogenic steps but cannot release free glucose into circulation due to lack of glucose-6-phosphatase.
Which enzyme deficiency would impair the conversion of lactate to glucose?
Pyruvate carboxylase
Lactate is converted to pyruvate, which must then be carboxylated to oxaloacetate by pyruvate carboxylase.
What hormone directly increases expression of phosphoenolpyruvate carboxykinase (PEPCK)?
Glucagon
Glucagon increases transcription of PEPCK during fasting, promoting gluconeogenesis.
What energy source is required for gluconeogenesis to proceed?
ATP and GTP
Gluconeogenesis is energy-intensive, requiring 6 ATP equivalents per glucose produced.
During gluconeogenesis, how many molecules of pyruvate are needed to generate one glucose?
Two
Two pyruvate molecules provide the three-carbon units necessary to make one six-carbon glucose.
A patient with biotinidase deficiency will have impaired function of which gluconeogenic enzyme?
Pyruvate carboxylase
Pyruvate carboxylase depends on biotin as a coenzyme. Without biotin, gluconeogenesis stalls.
What happens to the activity of fructose-1,6-bisphosphatase in response to low AMP?
Increases
Low AMP means energy is high, favoring gluconeogenesis. AMP inhibits this enzyme, so less AMP = more activity.
Why is glycerol a gluconeogenic substrate but fatty acids are not?
Glycerol enters at DHAP; even-chain fatty acids become acetyl-CoA which cannot yield net glucose
Acetyl-CoA cannot be used for net glucose synthesis due to irreversible decarboxylation steps.
What is the role of NADH in gluconeogenesis?
Required to reduce 1,3-bisphosphoglycerate to glyceraldehyde-3-phosphate
This is one of the reversible steps that requires NADH as a reducing agent.
What would be the consequence of a genetic defect in PEP carboxykinase?
Inability to produce PEP from oxaloacetate, blocking gluconeogenesis
Without PEPCK, gluconeogenesis cannot proceed beyond oxaloacetate, resulting in hypoglycemia during fasting.
