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Questions and Answers
What is the process of conversion of lactate to glucose called?
What is the process of conversion of lactate to glucose called?
gluconeogenesis
In which organ does gluconeogenesis primarily occur?
In which organ does gluconeogenesis primarily occur?
liver
How many ATP molecules are expended during gluconeogenesis?
How many ATP molecules are expended during gluconeogenesis?
6
How many phosphate bonds are yielded by glycolysis?
How many phosphate bonds are yielded by glycolysis?
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What is a futile cycle in the context of glycolysis and gluconeogenesis?
What is a futile cycle in the context of glycolysis and gluconeogenesis?
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What is the role of fructose-1,6-bisphosphatase in gluconeogenesis?
What is the role of fructose-1,6-bisphosphatase in gluconeogenesis?
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Glycolysis and gluconeogenesis can happen simultaneously.
Glycolysis and gluconeogenesis can happen simultaneously.
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Which enzyme catalyzes the formation of glucose-6-phosphate from glucose?
Which enzyme catalyzes the formation of glucose-6-phosphate from glucose?
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Which of the following enzymes are involved in bypass reactions of gluconeogenesis? (Select all that apply)
Which of the following enzymes are involved in bypass reactions of gluconeogenesis? (Select all that apply)
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What activates Pyruvate Carboxylase in gluconeogenesis?
What activates Pyruvate Carboxylase in gluconeogenesis?
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What does the Cori cycle explain?
What does the Cori cycle explain?
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What is the primary purpose of gluconeogenesis in the body?
What is the primary purpose of gluconeogenesis in the body?
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Which of the following enzymes is NOT involved in the irreversible steps of glycolysis?
Which of the following enzymes is NOT involved in the irreversible steps of glycolysis?
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What type of reaction does glucose-6-phosphatase catalyze in gluconeogenesis?
What type of reaction does glucose-6-phosphatase catalyze in gluconeogenesis?
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Which of the following statements about gluconeogenesis is incorrect?
Which of the following statements about gluconeogenesis is incorrect?
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What is the role of gluconeogenesis in relation to fast twitch muscle fibers?
What is the role of gluconeogenesis in relation to fast twitch muscle fibers?
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Which organ is most associated with the enzyme glucose-6-phosphatase?
Which organ is most associated with the enzyme glucose-6-phosphatase?
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Which phrase best describes the nature of gluconeogenesis?
Which phrase best describes the nature of gluconeogenesis?
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What key factor differentiates gluconeogenesis from glycolysis regarding certain reactions?
What key factor differentiates gluconeogenesis from glycolysis regarding certain reactions?
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What is the effect of AMP on Phosphofructokinase in glycolysis?
What is the effect of AMP on Phosphofructokinase in glycolysis?
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What is the primary function of Protein Kinase A in the liver during low blood glucose levels?
What is the primary function of Protein Kinase A in the liver during low blood glucose levels?
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What role does fructose-2,6-bisphosphate play in the regulation of glycolysis?
What role does fructose-2,6-bisphosphate play in the regulation of glycolysis?
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When ATP is high in a cell, what is the likely metabolic pathway prevalent in the situation?
When ATP is high in a cell, what is the likely metabolic pathway prevalent in the situation?
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Which of the following describes the interaction between ATP and AMP concerning glycolysis and gluconeogenesis?
Which of the following describes the interaction between ATP and AMP concerning glycolysis and gluconeogenesis?
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What is the primary function of Pyruvate Carboxylase in the gluconeogenesis pathway?
What is the primary function of Pyruvate Carboxylase in the gluconeogenesis pathway?
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Which energy molecule is cleaved to help drive the formation of PEP by PEP Carboxykinase?
Which energy molecule is cleaved to help drive the formation of PEP by PEP Carboxykinase?
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What role does acetyl CoA play in the regulation of Pyruvate Carboxylase?
What role does acetyl CoA play in the regulation of Pyruvate Carboxylase?
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What is the significance of the free energy associated with the phosphate bonds in ATP during gluconeogenesis?
What is the significance of the free energy associated with the phosphate bonds in ATP during gluconeogenesis?
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What is the primary role of oxaloacetate in the context of gluconeogenesis?
What is the primary role of oxaloacetate in the context of gluconeogenesis?
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During the conversion of pyruvate to PEP, what molecular change occurs in the second step catalyzed by PEP Carboxykinase?
During the conversion of pyruvate to PEP, what molecular change occurs in the second step catalyzed by PEP Carboxykinase?
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How does a depletion of oxaloacetate affect the Krebs cycle?
How does a depletion of oxaloacetate affect the Krebs cycle?
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What is the outcome when the concentration of acetyl CoA is elevated during gluconeogenesis?
What is the outcome when the concentration of acetyl CoA is elevated during gluconeogenesis?
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What byproducts are generated alongside the formation of PEP from oxaloacetate by the action of PEP Carboxykinase?
What byproducts are generated alongside the formation of PEP from oxaloacetate by the action of PEP Carboxykinase?
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What is the main role of phosphofructokinase in glycolysis?
What is the main role of phosphofructokinase in glycolysis?
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What distinguishes the gluconeogenesis process from glycolysis?
What distinguishes the gluconeogenesis process from glycolysis?
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Which substrate is required for the reaction catalyzed by fructose-1,6-bisphosphatase?
Which substrate is required for the reaction catalyzed by fructose-1,6-bisphosphatase?
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What is required for the bypass of the Pyruvate Kinase reaction in gluconeogenesis?
What is required for the bypass of the Pyruvate Kinase reaction in gluconeogenesis?
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Which statement about phospho-enolpyruvate (PEP) is correct?
Which statement about phospho-enolpyruvate (PEP) is correct?
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Which enzyme functions as a translocase in the context of G-6-Pase?
Which enzyme functions as a translocase in the context of G-6-Pase?
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What does the reaction catalyzed by Pyruvate Kinase produce?
What does the reaction catalyzed by Pyruvate Kinase produce?
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Which of the following substrates is not part of the reaction catalyzed by fructose-1,6-bisphosphatase?
Which of the following substrates is not part of the reaction catalyzed by fructose-1,6-bisphosphatase?
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What role does ATP play in the activity of phosphofructokinase?
What role does ATP play in the activity of phosphofructokinase?
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Which process does NOT utilize phosphofructokinase as an enzyme?
Which process does NOT utilize phosphofructokinase as an enzyme?
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What is the primary source of pyruvate for gluconeogenesis during fasting?
What is the primary source of pyruvate for gluconeogenesis during fasting?
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Which of these enzymes catalyzes the conversion of pyruvate to oxaloacetate in gluconeogenesis?
Which of these enzymes catalyzes the conversion of pyruvate to oxaloacetate in gluconeogenesis?
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What is one significant source of glycerol for gluconeogenesis?
What is one significant source of glycerol for gluconeogenesis?
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How many ATP equivalents are expended during gluconeogenesis?
How many ATP equivalents are expended during gluconeogenesis?
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What would occur if glycolysis and gluconeogenesis were both active in a cell?
What would occur if glycolysis and gluconeogenesis were both active in a cell?
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What is the function of Fructose-1,6-bisphosphatase in gluconeogenesis?
What is the function of Fructose-1,6-bisphosphatase in gluconeogenesis?
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In gluconeogenesis, which molecule is converted to glucose-6-phosphate by which enzyme?
In gluconeogenesis, which molecule is converted to glucose-6-phosphate by which enzyme?
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Which product of glycolysis is NOT a substrate for gluconeogenesis?
Which product of glycolysis is NOT a substrate for gluconeogenesis?
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What role does NAD+ play in the gluconeogenesis pathway?
What role does NAD+ play in the gluconeogenesis pathway?
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What connects amino acid catabolism to gluconeogenesis?
What connects amino acid catabolism to gluconeogenesis?
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What are the primary metabolic fates of glucose in the body?
What are the primary metabolic fates of glucose in the body?
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Which statement accurately describes glycolysis?
Which statement accurately describes glycolysis?
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What occurs to pyruvate under anaerobic conditions?
What occurs to pyruvate under anaerobic conditions?
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What is the primary role of the liver in carbohydrate metabolism?
What is the primary role of the liver in carbohydrate metabolism?
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Which co-factor is essential in the glycolytic pathway for the oxidation reaction?
Which co-factor is essential in the glycolytic pathway for the oxidation reaction?
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Which of the following correctly describes a consequence of reduced NAD?
Which of the following correctly describes a consequence of reduced NAD?
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How is glucose utilized by the body during intense exercise?
How is glucose utilized by the body during intense exercise?
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Which compound is formed when pyruvate is reduced during anaerobic glycolysis?
Which compound is formed when pyruvate is reduced during anaerobic glycolysis?
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What is the end product of lactate conversion in tissues after exercise?
What is the end product of lactate conversion in tissues after exercise?
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Which cycle utilizes pyruvate after lactate conversion?
Which cycle utilizes pyruvate after lactate conversion?
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What is the primary metabolic fate of lactate in the brain?
What is the primary metabolic fate of lactate in the brain?
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What product results from anaerobic metabolism of pyruvate in certain organisms?
What product results from anaerobic metabolism of pyruvate in certain organisms?
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Which process generates ATP from glucose without oxygen?
Which process generates ATP from glucose without oxygen?
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What reaction is catalyzed by Alcohol Dehydrogenase?
What reaction is catalyzed by Alcohol Dehydrogenase?
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Which of the following is a product of glycolysis?
Which of the following is a product of glycolysis?
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What is the ATP yield from the anaerobic catabolism of glucose?
What is the ATP yield from the anaerobic catabolism of glucose?
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What process occurs in astrocytes surrounding neurons in the brain?
What process occurs in astrocytes surrounding neurons in the brain?
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Which cofactor is produced during the conversion of pyruvate to lactate?
Which cofactor is produced during the conversion of pyruvate to lactate?
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What distinguishes glucokinase from hexokinase in terms of glucose affinity?
What distinguishes glucokinase from hexokinase in terms of glucose affinity?
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How does insulin affect glucokinase activity in the liver?
How does insulin affect glucokinase activity in the liver?
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What metabolic state does glucokinase primarily facilitate in the liver?
What metabolic state does glucokinase primarily facilitate in the liver?
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What type of conversion does Triose Phosphate Isomerase (TIM) catalyze?
What type of conversion does Triose Phosphate Isomerase (TIM) catalyze?
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What factor regulates the activity of glucokinase in the liver?
What factor regulates the activity of glucokinase in the liver?
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Which residue in Triose Phosphate Isomerase is primarily involved in acid/base catalysis?
Which residue in Triose Phosphate Isomerase is primarily involved in acid/base catalysis?
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Which role does glucose-6-phosphatase serve in glucose metabolism?
Which role does glucose-6-phosphatase serve in glucose metabolism?
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What product is generated from glyceraldehyde-3-phosphate by Glyceraldehyde-3-phosphate Dehydrogenase?
What product is generated from glyceraldehyde-3-phosphate by Glyceraldehyde-3-phosphate Dehydrogenase?
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Which intermediate is formed during the conversion of dihydroxyacetone phosphate to glyceraldehyde-3-phosphate?
Which intermediate is formed during the conversion of dihydroxyacetone phosphate to glyceraldehyde-3-phosphate?
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What ion is required for the reaction catalyzed by Glyceraldehyde-3-phosphate Dehydrogenase?
What ion is required for the reaction catalyzed by Glyceraldehyde-3-phosphate Dehydrogenase?
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What structural change is involved in the aldose/ketose conversion mediated by TIM?
What structural change is involved in the aldose/ketose conversion mediated by TIM?
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Which of the following reactions is catalyzed by Aldolase?
Which of the following reactions is catalyzed by Aldolase?
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Which molecule's concentration favors the formation of dihydroxyacetone-P?
Which molecule's concentration favors the formation of dihydroxyacetone-P?
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Which enzyme facilitates the conversion of glyceraldehyde-3-phosphate and inorganic phosphate to 1,3-bisphosphoglycerate?
Which enzyme facilitates the conversion of glyceraldehyde-3-phosphate and inorganic phosphate to 1,3-bisphosphoglycerate?
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Which reaction mechanism is employed by Triose Phosphate Isomerase during its function?
Which reaction mechanism is employed by Triose Phosphate Isomerase during its function?
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What is the primary function of Phosphoglycerate Mutase in the glycolytic pathway?
What is the primary function of Phosphoglycerate Mutase in the glycolytic pathway?
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Which ions are essential for the activity of Enolase?
Which ions are essential for the activity of Enolase?
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What type of reaction does Pyruvate Kinase catalyze?
What type of reaction does Pyruvate Kinase catalyze?
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During the reaction catalyzed by Enolase, what is produced alongside phosphoenolpyruvate?
During the reaction catalyzed by Enolase, what is produced alongside phosphoenolpyruvate?
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What happens to the unstable enol formed from phosphoenolpyruvate in the action of Pyruvate Kinase?
What happens to the unstable enol formed from phosphoenolpyruvate in the action of Pyruvate Kinase?
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Which substrate is necessary for the reaction catalyzed by Pyruvate Kinase?
Which substrate is necessary for the reaction catalyzed by Pyruvate Kinase?
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Which enzyme catalyzes the formation of 2-phosphoglycerate from 3-phosphoglycerate?
Which enzyme catalyzes the formation of 2-phosphoglycerate from 3-phosphoglycerate?
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What role do Mg++ ions play in the catalytic action of Enolase?
What role do Mg++ ions play in the catalytic action of Enolase?
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Which of the following is a byproduct of the reaction catalyzed by Pyruvate Kinase?
Which of the following is a byproduct of the reaction catalyzed by Pyruvate Kinase?
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What is the relationship between the removal of Pi from PEP and the formation of pyruvate?
What is the relationship between the removal of Pi from PEP and the formation of pyruvate?
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Study Notes
Gluconeogenesis Overview
- Conversion of lactate to glucose via gluconeogenesis utilizes glycolytic reactions in reverse.
- Occurs primarily in the liver; also in kidneys and small intestine under specific conditions.
- This pathway maintains blood glucose levels during fasting or low carbohydrate intake.
Energy Requirements and Bypasses
- Gluconeogenesis requires energy input, specifically ATP.
- Three irreversible glycolysis reactions must be bypassed:
- Hexokinase (or Glucokinase)
- Phosphofructokinase
- Pyruvate Kinase
- Two bypasses involve hydrolysis reactions, utilizing enzymes like glucose-6-phosphatase and fructose-1,6-bisphosphatase.
Key Enzymatic Reactions
- Hexokinase/Glucokinase: Converts glucose + ATP to glucose-6-phosphate + ADP.
- Glucose-6-Phosphatase: Converts glucose-6-phosphate + H2O to glucose + Pi.
- Phosphofructokinase: Converts fructose-6-phosphate + ATP to fructose-1,6-bisphosphate + ADP.
- Fructose-1,6-bisphosphatase: Converts fructose-1,6-bisphosphate + H2O to fructose-6-phosphate + Pi.
- Pyruvate Carboxylase: Converts pyruvate + HCO3- + ATP to oxaloacetate + ADP + Pi.
- PEP Carboxykinase: Converts oxaloacetate + GTP to PEP + GDP + CO2.
Substrates and Inputs
- Major sources for gluconeogenesis during fasting include amino acid catabolism and glycerol from fat breakdown.
- Amino acids converted to pyruvate, oxaloacetate, or precursors for gluconeogenesis, especially from muscle.
Regulation Mechanisms
- Glycolysis and gluconeogenesis are regulated to prevent futile cycles, saving energy.
- Local Regulation: Reciprocal allosteric regulation by AMP and ATP.
- Phosphofructokinase is inhibited by ATP, activated by AMP; Fructose-1,6-bisphosphatase is inhibited by AMP.
- Global Regulation: The hormone glucagon triggers a cAMP cascade in liver, inhibiting glycolysis while stimulating gluconeogenesis.
- Protein Kinase A activates gluconeogenesis enzymes and inhibits glycolysis enzymes such as pyruvate kinase.
Cori Cycle
- Explains glucose consumption by muscles and the lactate production process.
- Lactate is transported to the liver for glucose synthesis through gluconeogenesis.
Summary of Energy Transactions
- Glycolysis yields 2 ATP, while gluconeogenesis expends 6 ATP (net expended ~P of 4 in the process).
- Glycolysis: glucose + 2 NAD+ + 2 ADP + 2 Pi → 2 pyruvate + 2 NADH + 2 ATP.
- Gluconeogenesis: 2 pyruvate + 2 NADH + 4 ATP + 2 GTP → glucose + 2 NAD+ + 4 ADP + 2 GDP + 6 Pi.
Interplay of Metabolic Pathways
- Glycolysis and gluconeogenesis are spontaneity driven; conditions ensure that they don't operate simultaneously.
- Fructose-2,6-bisphosphate functions as a key regulator, favoring glycolysis when glucose is abundant and inhibiting gluconeogenesis.
Gluconeogenesis Overview
- Converts lactate to glucose, primarily in the liver.
- Also occurs in kidneys and small intestine under specific conditions.
- Utilizes some glycolytic reactions in reverse, alongside unique reactions for synthesizing glucose.
- Requires energy input in the form of ATP.
- Maintains glucose levels in blood even without dietary intake, supplying fast-twitch muscle fibers.
Key Enzymes and Bypass Reactions
- Key Glycolysis Enzymes: Hexokinase, Phosphofructokinase, Pyruvate Kinase – these have large negative Gibbs free energy values, making them essentially irreversible.
- Gluconeogenesis must bypass these steps using different enzymes:
- Hexokinase/Glucokinase vs. Glucose-6-phosphatase: Converts glucose-6-phosphate to glucose.
- Phosphofructokinase vs. Fructose-1,6-bisphosphatase: Converts fructose-1,6-bisphosphate to fructose-6-phosphate.
- Pyruvate Kinase vs. Pyruvate Carboxylase and PEP Carboxykinase: Converts pyruvate to phosphoenolpyruvate (PEP).
Enzyme Details
- Glucose-6-Phosphatase: Found in the endoplasmic reticulum of liver cells, hydrolyzes glucose-6-phosphate to glucose.
- Fructose-1,6-bisphosphatase: Catalyzes conversion of fructose-1,6-bisphosphate to fructose-6-phosphate.
- Pyruvate Carboxylase and PEP Carboxykinase: Work together to convert pyruvate to oxaloacetate, then to PEP in a two-step process requiring ATP and GTP.
Energy Dynamics
- Gluconeogenesis costs 6 high-energy phosphate bonds (4 ATP, 2 GTP) to produce glucose from 2 pyruvate.
- Glycolysis yields 2 high-energy phosphates.
- If both pathways were active simultaneously, they would waste 4 high-energy phosphates per cycle, termed a "futile cycle".
Regulation Mechanisms
- Local Control: Reciprocal allosteric regulation by adenine nucleotides; ATP inhibits phosphofructokinase but stimulates fructose-1,6-bisphosphatase, ensuring energy conservation.
-
Global Control:
- Hormonal regulation by glucagon during low blood glucose levels via a cAMP cascade.
- Protein Kinase A phosphorylates enzymes, inhibiting glycolysis and stimulating gluconeogenesis.
- Enhances transcription of PEP Carboxykinase to increase gluconeogenesis.
Substrates for Gluconeogenesis
- Major substrates include:
- Amino acids, mainly derived from muscle protein catabolism.
- Glycerol from triglyceride breakdown in adipose tissue.
- Oxaloacetate depletion prevents acetyl CoA from entering the Krebs Cycle, crucial for gluconeogenesis during fasting.
Summary of Reaction Pathways
- Glycolysis: Converts glucose to pyruvate, yielding 2 ATP and 2 NADH.
- Gluconeogenesis: Converts 2 pyruvate back to glucose, consuming 6 high-energy phosphates.
Enzyme Names
- Gluconeogenesis enzymes listed in red, glycolysis enzymes in blue, illustrating their coordinated regulation and cross-utilization in carbohydrate metabolism.
Carbohydrate Metabolism
- Primary source of dietary carbohydrates for humans is starch from plants, supplemented by glycogen from animals, sucrose, and lactose.
- Digestion converts carbohydrates into monosaccharides, primarily glucose, which is transported to the liver.
- Liver plays a crucial role in storage and distribution of glucose and energy sources in the body.
Fates of Dietary Glucose
- Glucose is catabolized for ATP production, stored as glycogen in liver and muscle, or converted to fatty acids for triglyceride storage in adipose tissue.
Glycolysis
- Glycolysis cleaves glucose (C6H12O6) into two pyruvate molecules (C3H3O3-) while producing a net of 2 ATP per glucose.
- NAD functions as an electron acceptor; its limited supply necessitates its re-oxidation for glycolysis to continue.
Anaerobic Glycolysis
- In absence of oxygen, pyruvate is reduced to lactate, allowing glycolysis to continue in heavily exercising muscles.
- This conversion helps regenerate NAD from NADH, essential for continued ATP production.
Key Enzymatic Reactions in Glycolysis
- Triose Phosphate Isomerase (TIM): Converts dihydroxyacetone phosphate to glyceraldehyde-3-phosphate to facilitate glycolysis progression.
- Glyceraldehyde-3-phosphate Dehydrogenase: Catalyzes the conversion of glyceraldehyde-3-phosphate to 1,3-bisphosphoglycerate, using NAD+.
- Phosphoglycerate Mutase: Shifts phosphate from C3 to C2 to form 2-phosphoglycerate.
- Enolase: Dehydrates 2-phosphoglycerate to phosphoenolpyruvate, a reaction requiring Mg++ ions.
- Pyruvate Kinase: Catalyzes the conversion of phosphoenolpyruvate to pyruvate, producing ATP in the process.
Lactate and Its Role
- Lactate generated can be re-converted to pyruvate by lactate dehydrogenase in other tissues, facilitating energy production.
- Plays a crucial role as a fuel source for cardiac muscle and brain neurons, where astrocytes convert glucose to lactate for neuronal uptake.
Alcohol Fermentation
- Some anaerobic organisms convert pyruvate into ethanol, excreting it as a waste product.
- NADH is oxidized back to NAD+ in this process via alcohol dehydrogenase.
Summary of Glycolysis
- Overall equation for glycolysis:
- Glucose + 2 NAD+ + 2 ADP + 2 Pi → 2 Pyruvate + 2 NADH + 2 ATP
- Fermentation equation from glucose to lactate:
- Glucose + 2 ADP + 2 Pi → 2 Lactate + 2 ATP
- Anaerobic metabolism yields only 2 ATP.
Glucokinase vs. Hexokinase
- Glucokinase, found in the liver, has a high KM for glucose and is active at high glucose concentrations.
- It is not inhibited by glucose-6-phosphate and allows glucose uptake in high concentrations.
- Subject to regulation via glucokinase regulatory protein (GKRP), which alters based on metabolic state, allowing modulation of glucose phosphorylation.
Glucose Metabolism in Liver
- Glucose-6-phosphatase catalyzes the release of inorganic phosphate from glucose-6-phosphate, regulating glucose homeostasis.
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Description
This quiz explores the process of gluconeogenesis, highlighting the conversion of lactate to glucose and the pathways involved. Understand the role of ATP in this metabolic process and its importance in maintaining blood glucose levels, especially during fasting. Test your knowledge on the reactions and significance of this essential biochemical pathway.
