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Questions and Answers
What occurs during lactic acid fermentation in oxygen-poor tissue?
What occurs during lactic acid fermentation in oxygen-poor tissue?
Which molecule cannot serve as a precursor for gluconeogenesis?
Which molecule cannot serve as a precursor for gluconeogenesis?
How can gluconeogenic substrates that are metabolized directly to oxaloacetate benefit the energy consumption during gluconeogenesis?
How can gluconeogenic substrates that are metabolized directly to oxaloacetate benefit the energy consumption during gluconeogenesis?
What is the first step when oxaloacetate needs to enter the cytosol?
What is the first step when oxaloacetate needs to enter the cytosol?
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What role does the malate-aspartate shuttle play in gluconeogenesis?
What role does the malate-aspartate shuttle play in gluconeogenesis?
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What is the result of oxidizing lactate to pyruvate?
What is the result of oxidizing lactate to pyruvate?
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Which substrates can produce oxaloacetate either directly or through the citric acid cycle?
Which substrates can produce oxaloacetate either directly or through the citric acid cycle?
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What happens to oxaloacetate after it is reduced to malate in the cytosol?
What happens to oxaloacetate after it is reduced to malate in the cytosol?
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What is the net effect of a futile cycle involving pyruvate and phosphoenolpyruvate?
What is the net effect of a futile cycle involving pyruvate and phosphoenolpyruvate?
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How many ATP equivalents are required to convert one pyruvate to phosphoenolpyruvate?
How many ATP equivalents are required to convert one pyruvate to phosphoenolpyruvate?
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Which enzyme catalyzes the conversion of 3-phosphoglycerate to 1,3-bisphosphoglycerate?
Which enzyme catalyzes the conversion of 3-phosphoglycerate to 1,3-bisphosphoglycerate?
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What occurs when one pyruvate molecule is converted into two G3P molecules?
What occurs when one pyruvate molecule is converted into two G3P molecules?
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Which enzyme in glycolysis is responsible for synthesizing fructose 1,6-bisphosphate?
Which enzyme in glycolysis is responsible for synthesizing fructose 1,6-bisphosphate?
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What is the role of the enzyme fructose-1,6-bisphosphatase in gluconeogenesis?
What is the role of the enzyme fructose-1,6-bisphosphatase in gluconeogenesis?
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Which of the following statements is true regarding the regulation of glycolysis and gluconeogenesis?
Which of the following statements is true regarding the regulation of glycolysis and gluconeogenesis?
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What happens to dihydroxyacetone phosphate (DHAP) in the gluconeogenesis pathway?
What happens to dihydroxyacetone phosphate (DHAP) in the gluconeogenesis pathway?
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What is the primary role of insulin in relation to glycolysis?
What is the primary role of insulin in relation to glycolysis?
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Which hormone is primarily involved in increasing blood glucose levels during fasting?
Which hormone is primarily involved in increasing blood glucose levels during fasting?
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How does F2,6BP affect PFK-1 in glycolysis?
How does F2,6BP affect PFK-1 in glycolysis?
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What is the effect of glucagon on PKA?
What is the effect of glucagon on PKA?
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During which physiological state is insulin released?
During which physiological state is insulin released?
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Which enzyme is specifically inhibited by insulin to prevent gluconeogenesis?
Which enzyme is specifically inhibited by insulin to prevent gluconeogenesis?
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What is the main action of glucagon after binding to its receptor?
What is the main action of glucagon after binding to its receptor?
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How does insulin affect glycolysis when energy levels are high?
How does insulin affect glycolysis when energy levels are high?
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What role does ATP play in the regulation of phosphofructokinase-1 (PFK-1)?
What role does ATP play in the regulation of phosphofructokinase-1 (PFK-1)?
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Which of the following molecules is a potent allosteric stimulator of PFK-1 activity?
Which of the following molecules is a potent allosteric stimulator of PFK-1 activity?
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What happens to PFK-1 activity when ATP levels drop?
What happens to PFK-1 activity when ATP levels drop?
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How does citrate affect PFK-1 activity?
How does citrate affect PFK-1 activity?
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What is the role of phosphofructokinase-2 (PFK-2) in glycolysis?
What is the role of phosphofructokinase-2 (PFK-2) in glycolysis?
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What is the relationship between ADP and PFK-1 activity?
What is the relationship between ADP and PFK-1 activity?
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Which enzyme is responsible for the degradation of fructose 2,6-bisphosphate?
Which enzyme is responsible for the degradation of fructose 2,6-bisphosphate?
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Where does the citric acid cycle occur in the cell?
Where does the citric acid cycle occur in the cell?
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What is one reason the liver uses ATP for gluconeogenesis despite the cost?
What is one reason the liver uses ATP for gluconeogenesis despite the cost?
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Which enzyme in glycolysis is primarily inhibited by its product glucose 6-phosphate in most cells?
Which enzyme in glycolysis is primarily inhibited by its product glucose 6-phosphate in most cells?
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How does the liver regulate glycolysis differently than other tissues?
How does the liver regulate glycolysis differently than other tissues?
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What happens to glycolytic flux when product levels are excessively high in tissues that do not perform gluconeogenesis?
What happens to glycolytic flux when product levels are excessively high in tissues that do not perform gluconeogenesis?
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Which of the following is NOT an allosteric inhibitor of pyruvate kinase?
Which of the following is NOT an allosteric inhibitor of pyruvate kinase?
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What metabolic pathway primarily provides ATP for red blood cells?
What metabolic pathway primarily provides ATP for red blood cells?
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What is the role of feedback inhibition in glycolysis in tissues like muscle and red blood cells?
What is the role of feedback inhibition in glycolysis in tissues like muscle and red blood cells?
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Why is it important for the regulation of glycolysis to be tightly controlled in tissues that express gluconeogenesis enzymes?
Why is it important for the regulation of glycolysis to be tightly controlled in tissues that express gluconeogenesis enzymes?
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What role does fructose 2,6-bisphosphate (F2,6BP) play in muscle glycolysis?
What role does fructose 2,6-bisphosphate (F2,6BP) play in muscle glycolysis?
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In muscle cells, what primarily regulates the levels of fructose 2,6-bisphosphate (F2,6BP)?
In muscle cells, what primarily regulates the levels of fructose 2,6-bisphosphate (F2,6BP)?
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What is the primary effect of a sudden increase in glucose 6-phosphate levels in a muscle cell?
What is the primary effect of a sudden increase in glucose 6-phosphate levels in a muscle cell?
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Which enzyme is primarily affected by the accumulation of fructose 2,6-bisphosphate (F2,6BP) in muscle cells?
Which enzyme is primarily affected by the accumulation of fructose 2,6-bisphosphate (F2,6BP) in muscle cells?
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What is the rationale for the feedback inhibition of hexokinase in glycolysis?
What is the rationale for the feedback inhibition of hexokinase in glycolysis?
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Which compound serves as a sign of low energy stores and activates phosphofructokinase-1 (PFK-1)?
Which compound serves as a sign of low energy stores and activates phosphofructokinase-1 (PFK-1)?
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How do liver cells differ from muscle cells in their regulation of glycolysis?
How do liver cells differ from muscle cells in their regulation of glycolysis?
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What happens to the PFK-1 activity when fructose 6-phosphate accumulates in muscle cells?
What happens to the PFK-1 activity when fructose 6-phosphate accumulates in muscle cells?
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Study Notes
Gluconeogenesis Introduction
- Gluconeogenesis is the process of building glucose from two pyruvate molecules
- It requires more energy (2 NADH and 6 ATP) than glycolysis releases
- This process is vital during fasting or for recycling glycolysis end products
- Gluconeogenesis and glycolysis must be regulated to prevent energy loss
Gluconeogenesis
- Primarily takes place in the liver, although other cell types can also support it
- This compartmentalization reflects the liver's role in providing fuel during fasting
- Gluconeogenesis shares some enzymes with glycolysis, but is not simply glycolysis in reverse
- Gluconeogenesis requires unique enzymes to bypass three irreversible steps in glycolysis
- These bypass reactions are also irreversible and are catalyzed by different, unique enzymes
Bypass Reactions in Gluconeogenesis
- For each of the three irreversible steps of glycolysis, unique enzymes are used by gluconeogenesis
- These bypass reactions are also irreversible and catalyzed by distinct, unique enzymes
- The other seven reversible reactions of glycolysis are shared with gluconeogenesis
The First Set of Bypass Reactions
- Pyruvate is converted to oxaloacetate through pyruvate carboxylase
- This reaction consumes one ATP molecule and occurs in the mitochondrial matrix
- Oxaloacetate is then converted to phosphoenolpyruvate by phosphoenolpyruvate carboxykinase (PEPCK)
- This reaction consumes one GTP molecule and occurs either in the mitochondrial or cytosolic compartments
Alternate Entry Points of Gluconeogenesis
- Other molecules beyond pyruvate (like alanine and lactate) can contribute to gluconeogenesis
- Alanine is converted to pyruvate through deamination
- Lactate is reversibly reduced to pyruvate for gluconeogenesis
- Some substrates are directly metabolized into oxaloacetate without first becoming pyruvate
- Examples include many amino acids and odd-chain fatty acids
- Acetyl-CoA does not serve as a precursor for gluconeogenesis
The Cori Cycle
- It's a pathway connecting glycolysis and gluconeogenesis
- During strenuous exercise, muscles produce lactate, which is transported to the liver
- In the liver, lactate is converted back to pyruvate and used in gluconeogenesis
- The generated glucose is released to the bloodstream and can be used by muscles
Regulation of Glucose Metabolism
- Glycolysis and gluconeogenesis are regulated to maintain stable metabolite levels
- Hexokinase, phosphofructokinase-1, and pyruvate kinase are regulated mainly in non-gluconeogenic tissues
- Hexokinase is inhibited by its product (glucose-6-phosphate)
- Pyruvate kinase is inhibited by its product (ATP) and by acetyl-CoA and long-chain fatty acids
- Phosphofructokinase-1 (PFK-1) is the most regulated enzyme, inhibited by ATP and activated by ADP and AMP
- The metabolite citrate also inhibits PFK-1
- Fructose 2,6-bisphosphate (F2,6BP) is a potent activator of PFK-1
- F2,6BP is generated by PFK-2 and degraded by FBPase-2
- Covalent regulation (activation and deactivation by phosphorylation/dephosphorylation) also affects glycolysis regulation, especially in the liver
- Insulin activates the enzyme phosphoprotein phosphatase-1 (PP1)
- Glucagon and epinephrine activate protein kinase A (PKA) which leads to deactivating PFK-2 and activating FBPase-2
- This complex regulation maintains blood glucose homeostasis
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Description
This quiz covers the essential concepts of gluconeogenesis, including its biochemical pathway and its critical role during fasting. Learn about the unique enzymes involved and how gluconeogenesis differs from glycolysis. Test your understanding of the regulation of these metabolic processes.