Chapter 17: Gluconeogenesis Flashcards
Where are the major sites of gluconeogenesis?
Liver and kidneys
Gluconeogenesis is important for maintaining ________ during _____.
Normal blood glucose levels during starvation
Brain uses only glucose, therefore the liver essentially works to…
Make the brain happy by maintaing blood glucose levels
Most of the glucose generated in gluconeogenesis is used by _____ and ______.
Brain and contracting muscle
Gluconeogenesis converts ______ to ______.
Pyruvate to Glucose
What are the three precursors for gluconeogenesis?
- Lactate (muscle)
- Amino acids
- Glycerol (adipose tissue)
Not present in glycolysis
Glycerol enters gluconeogenesis as…
Dihydroxyacetone phosphate
The 3 irreversible reactions of glycolysis are…
Bypassed in gluconeogenesis by new steps/enzymes
7/10 Enzymes are the same
Pyruvate kinase reaction (irreversible) of glycolysis is bypassed by:
- Pyruvate carboxylase
- Phosphoenolpyruvate carboxykinase (PEP)
Step 1 of gluconeogenesis
Pyruvate carboxylated to oxaloacetate by pyruvate carboxylase (mitochondrial enzyme)
First step of gluconeogenesis occurs in the…
Mitochondrial matrix
Oxaloacetate is transported to the cytosol as…
Malate
Once reoxidized in the cytoplasm, oxaloacetate is decarboxylated and phosphorylated to…
PEP by PEP carboxykinase
In glycolysis, PFK controls the rate. What enzyme controls the rate of gluconeogenesis, bypassing the PFK reaction?
Fructose 1,6-bisphosphatase (FBPase)
*Allosteric enzyme that controls gluconeogenesis
Which enzyme is critical for free glucose levels?
Glucose 6-phosphatase
*Reverse of hexokinase
Free glucose is generated mainly in the…
Liver
Glucose 6-phosphatase is present only in…
Liver and kidney
Glucose 6-phosphate is hydrolyzed to ______ in the _______.
Glucose in the ER lumen
When glucose is abundant, which process will predominate?
Glycolysis
When glucose is scarce, which process will take over?
Gluconeogenesis
Both glycolysis and gluconeogenesis are highly _____ under cellular conditions.
Exergonic
When synthesizing glucose from pyruvate, __________ are spent.
6 high transfer-potential phosphoryl transfer groups (4 ATP and 2 GTP)
What is lactic acidosis?
Accumulation of lactic acid in the blood (lowers the pH) which is caused by a deficiency in gluconeogenic enzymes
What is hypoglycemia?
Low blood glucose levels
-Liver cannot produce glucose to maintain normal glucose levels
Gluconeogenesis and glycolysis are…
Coordinated
Rate of glycolysis is determined by…
Glucose concentration
Rate of gluconeogenesis is dependent on…
Lactate concentration and other precursors
When high levels of AMP…
Low energy
Glycolysis turned on
Gluconeogenesis turned off
(AMP stimulates PFK, but inhibits Fructose 1,6-bisphosphatase)
When high levels of ATP…
High energy
Turn off glycolysis
(Citrate inhibits PFK)
Citrate is an activator of ________ and promotes ________.
Fructose 1,6-bisphosphatase and promotes gluconeogenesis
Pyruvate carboxylase - what activates/inhibits?
Activated by ADP
Inhibited by acetyl CoA
PEP carboxykinase is inhibited by…
ADP
If ATP is required, ________ predominates.
Glycolysis
If glucose is required, ________ is favored.
Gluconeogenesis
Blood glucose levels regulate glycolysis and gluconeogenesis in _____ by changing _______.
Liver
Fructose 2,6-bisphosphate levels
Fructose 2,6-bisphosphatase is an ________ and stimulates _______. Also inhibits __________.
Allosteric regulator
Stimulates PFK
Inhibits Fructose1,6-bisphosphatase
At high blood glucose levels, fructose 2,6-bisphosphate levels _____.
Increase
When blood glucose levels are low, fructose 2,6-bisphosphate is converted to…
Fructose 6-phosphate
PFK2 and FBPase2 are present in a single polypeptide chain. This is a ________ enzyme with three domains. What are they?
Bifunctional enzyme
Domains: N-terminal regulatory, kinase and phosphatase
PFK2 and FBPase2 are controlled ________ by ________ of a single serine residue.
Reciprocally by phosphorylation
Phosphorylation activates _____ and inhibits _____ to turn off _______.
FBPase 2 activated
PFK2 inhibited
Turns off glycolysis
When glucose is scarce, _______ levels rise in the blood and trigger a cascade of _______ to activate ____.
Which process is active? (Glycolysis/Gluconeogenesis)
Glucagon levels rise, trigger cyclic AMP and activate PKA
Gluconeogenesis is active
When glucose is abudant, the enzyme becomes dephosphorylated, which activates _______ and inhibits ________.
Which process is active? (Glycolysis/Gluconeogenesis)
Activates PFK2
Inhibits FBPase2
Glycolysis is active
Insulin levels rise after each meal in response to __________. Insulin promotes _______.
Increasing blood glucose levels
Promotes glycolysis
Glucagon levels rise during ______ when glucose is _____. This promotes…
Fasting when glucose is scarce
This promotes gluconeogenesis
Insulin normally inhibits _______. In type 2 diabetes, insulin _________. This condition is called __________.
Inhibits gluconeogenesis
Insulin fails to do this in type 2 diabetes. This is called insulin resistance.
(Liver does not react to insulin, it just keeps making glucose, even if starving)
What two factors enhance insulin sensitivity?
Exercise and diet
What is the Cori cycle?
Lactate produced by muscle during contraction is released into the blood.
*Interrelationship between liver and muscle
Liver removes the lactate, converts to glucose via gluconeogenesis which is released into the blood and taken up by muscle.
What are the 3 major factors that control glycolysis and gluconeogenesis?
- ATP levels
- Citrate
- Blood glucose levels
Glycolysis:
- Major control point
- Fructose 2,6-bisphosphate
- AMP
- Citrate
- Hormonal activation by
- PFK
- Activates
- Activates
- Inhibits
- Insulin
Gluconeogenesis:
- Major control point
- Fructose 2,6-bisphosphate
- AMP
- Citrate
- Hormonal activation by
- FBPase
- Inhibits
- Inhibits
- Activates
- Glucagon
The hexokinase reaction of glycolysis is bypassed during gluconeogenesis by the enzyme:
Glucose 6-phosphatase
Which of the following molecules is NOT a precursor for gluconeogenesis?
Acetyl CoA
Which enzyme controls the rate of gluconeogenesis?
Fructose 1,6-bisphosphatase
Deficiencies in enzymes specific for gluconeogenesis lead to:
Lactic acidosis and hypoglycemia
When blood glucose levels are high, insulin activates _______ and stimulates _______.
Activates protein phosphatase-1; glycogen synthesis
Which enzyme converts pyruvate to oxaloacetate in gluconeogenesis?
Pyruvate carboxylase
Which compound is NOT a precursor for the synthesis of glucose by gluconeogenesis?
Acetyl CoA
Which enzyme controls the rate of gluconeogenesis?
Fructose 1,6-biphosphatase
Deficiencies in enzymes specific for gluconeogenesis lead to:
Lactic acidosis and hypoglycemia
What type of glycosidic bond causes the branching of glycogen?
alpha 1,6-glycosidic bond
Glycogen phosphorylase cleaves glycogen and produces:
Glucose 1-phosphate
When blood glucose levels are high, insulin activates____________
and stimulates _______________.
Protein phosphatase-1; glycogen synthesis
Which enzyme is specific for the gluconeogenesis pathway?
Phosphoenolpyruvate carboxykinase
The enzyme _______________ controls the rate of gluconeogenesis and is allosterically inhibited by high levels of _______________.
Fructose 1,6-bisphosphatase; fructose 2,6-bisphosphate
Glucagon ________________ glycogen degradation and signals the __________ state.
stimulates; fasted
Which enzyme is NOT specific for gluconeogenesis?
Phosphoglycerate mutase
. Gluconeogenesis occurs in the ____________ and is activated during ______________.
Liver; starvation
