Gluconeogenesis Overview

Questions and Answers

What is the process of conversion of lactate to glucose called?

gluconeogenesis

In which organ does gluconeogenesis primarily occur?

liver

How many ATP molecules are expended during gluconeogenesis?

How many phosphate bonds are yielded by glycolysis?

2 Signup and view all the answers

What is a futile cycle in the context of glycolysis and gluconeogenesis?

A cycle that would waste energy Signup and view all the answers

What is the role of fructose-1,6-bisphosphatase in gluconeogenesis?

It catalyzes the conversion of fructose-1,6-bisphosphate to fructose-6-phosphate. Signup and view all the answers

Glycolysis and gluconeogenesis can happen simultaneously.

False Signup and view all the answers

Which enzyme catalyzes the formation of glucose-6-phosphate from glucose?

hexokinase or glucokinase Signup and view all the answers

Which of the following enzymes are involved in bypass reactions of gluconeogenesis? (Select all that apply)

Fructose-1,6-bisphosphatase Signup and view all the answers

What activates Pyruvate Carboxylase in gluconeogenesis?

acetyl CoA Signup and view all the answers

What does the Cori cycle explain?

How glucose is consumed by muscles and converted back to glucose in the liver. Signup and view all the answers

What is the primary purpose of gluconeogenesis in the body?

To synthesize glucose from non-carbohydrate sources Signup and view all the answers

Which of the following enzymes is NOT involved in the irreversible steps of glycolysis?

Glucose-6-Phosphatase Signup and view all the answers

What type of reaction does glucose-6-phosphatase catalyze in gluconeogenesis?

Hydrolysis reaction Signup and view all the answers

Which of the following statements about gluconeogenesis is incorrect?

It can happen in the absence of ATP Signup and view all the answers

What is the role of gluconeogenesis in relation to fast twitch muscle fibers?

To maintain a glucose supply when dietary glucose is scarce Signup and view all the answers

Which organ is most associated with the enzyme glucose-6-phosphatase?

Liver Signup and view all the answers

Which phrase best describes the nature of gluconeogenesis?

It is primarily an anabolic process that builds glucose Signup and view all the answers

What key factor differentiates gluconeogenesis from glycolysis regarding certain reactions?

Irreversible steps must be bypassed in gluconeogenesis Signup and view all the answers

What is the effect of AMP on Phosphofructokinase in glycolysis?

Stimulates the enzyme's activity Signup and view all the answers

What is the primary function of Protein Kinase A in the liver during low blood glucose levels?

Stimulates gluconeogenesis and inhibits glycolysis Signup and view all the answers

What role does fructose-2,6-bisphosphate play in the regulation of glycolysis?

Stimulates Phosphofructokinase activity Signup and view all the answers

When ATP is high in a cell, what is the likely metabolic pathway prevalent in the situation?

Storage of glucose as glycogen Signup and view all the answers

Which of the following describes the interaction between ATP and AMP concerning glycolysis and gluconeogenesis?

ATP and AMP have opposite effects on glycolysis and gluconeogenesis Signup and view all the answers

What is the primary function of Pyruvate Carboxylase in the gluconeogenesis pathway?

Catalyzes the formation of oxaloacetate from pyruvate Signup and view all the answers

Which energy molecule is cleaved to help drive the formation of PEP by PEP Carboxykinase?

GTP Signup and view all the answers

What role does acetyl CoA play in the regulation of Pyruvate Carboxylase?

It allosterically activates the enzyme Signup and view all the answers

What is the significance of the free energy associated with the phosphate bonds in ATP during gluconeogenesis?

It drives the carboxylation reaction towards completion Signup and view all the answers

What is the primary role of oxaloacetate in the context of gluconeogenesis?

It is a limiting factor for the Krebs cycle Signup and view all the answers

During the conversion of pyruvate to PEP, what molecular change occurs in the second step catalyzed by PEP Carboxykinase?

CO2 is released during the transformation Signup and view all the answers

How does a depletion of oxaloacetate affect the Krebs cycle?

It halts the Krebs cycle completely Signup and view all the answers

What is the outcome when the concentration of acetyl CoA is elevated during gluconeogenesis?

It stimulates the activity of Pyruvate Carboxylase Signup and view all the answers

What byproducts are generated alongside the formation of PEP from oxaloacetate by the action of PEP Carboxykinase?

GTP and CO2 Signup and view all the answers

What is the main role of phosphofructokinase in glycolysis?

It catalyzes the conversion of fructose-6-P to fructose-1,6-bisP. Signup and view all the answers

What distinguishes the gluconeogenesis process from glycolysis?

Gluconeogenesis regenerates fructose-6-P from fructose-1,6-bisP. Signup and view all the answers

Which substrate is required for the reaction catalyzed by fructose-1,6-bisphosphatase?

Fructose-1,6-bisP Signup and view all the answers

What is required for the bypass of the Pyruvate Kinase reaction in gluconeogenesis?

Cleavage of two ~P bonds Signup and view all the answers

Which statement about phospho-enolpyruvate (PEP) is correct?

PEP has a higher negative DG of phosphate hydrolysis than ATP. Signup and view all the answers

Which enzyme functions as a translocase in the context of G-6-Pase?

Another subunit of G-6-Pase Signup and view all the answers

What does the reaction catalyzed by Pyruvate Kinase produce?

Pyruvate and ATP Signup and view all the answers

Which of the following substrates is not part of the reaction catalyzed by fructose-1,6-bisphosphatase?

ATP Signup and view all the answers

What role does ATP play in the activity of phosphofructokinase?

It is a substrate used to convert fructose-6-P to fructose-1,6-bisP. Signup and view all the answers

Which process does NOT utilize phosphofructokinase as an enzyme?

Facilitation of gluconeogenesis Signup and view all the answers

What is the primary source of pyruvate for gluconeogenesis during fasting?

Amino acid catabolism Signup and view all the answers

Which of these enzymes catalyzes the conversion of pyruvate to oxaloacetate in gluconeogenesis?

Pyruvate Carboxylase Signup and view all the answers

What is one significant source of glycerol for gluconeogenesis?

Hydrolysis of triacylglycerols Signup and view all the answers

How many ATP equivalents are expended during gluconeogenesis?

6 Signup and view all the answers

What would occur if glycolysis and gluconeogenesis were both active in a cell?

Futile cycling Signup and view all the answers

What is the function of Fructose-1,6-bisphosphatase in gluconeogenesis?

Catalyze the conversion of fructose-1,6-bisphosphate to fructose-6-phosphate Signup and view all the answers

In gluconeogenesis, which molecule is converted to glucose-6-phosphate by which enzyme?

Fructose-6-phosphate; Phosphoglucose Isomerase Signup and view all the answers

Which product of glycolysis is NOT a substrate for gluconeogenesis?

Glucose Signup and view all the answers

What role does NAD+ play in the gluconeogenesis pathway?

It provides reducing power to convert substrates Signup and view all the answers

What connects amino acid catabolism to gluconeogenesis?

Formation of pyruvate and oxaloacetate Signup and view all the answers

What are the primary metabolic fates of glucose in the body?

To be catabolised for ATP production or stored as glycogen. Signup and view all the answers

Which statement accurately describes glycolysis?

It cleaves a six-carbon glucose molecule into two three-carbon pyruvate molecules. Signup and view all the answers

What occurs to pyruvate under anaerobic conditions?

It is reduced to lactate. Signup and view all the answers

What is the primary role of the liver in carbohydrate metabolism?

To store and distribute glucose and other fuels. Signup and view all the answers

Which co-factor is essential in the glycolytic pathway for the oxidation reaction?

NAD Signup and view all the answers

Which of the following correctly describes a consequence of reduced NAD?

Inhibition of glycolysis. Signup and view all the answers

How is glucose utilized by the body during intense exercise?

Primarily utilized for ATP production through anaerobic glycolysis. Signup and view all the answers

Which compound is formed when pyruvate is reduced during anaerobic glycolysis?

Lactate Signup and view all the answers

What is the end product of lactate conversion in tissues after exercise?

Pyruvate Signup and view all the answers

Which cycle utilizes pyruvate after lactate conversion?

Citric Acid Cycle Signup and view all the answers

What is the primary metabolic fate of lactate in the brain?

Converted to pyruvate Signup and view all the answers

What product results from anaerobic metabolism of pyruvate in certain organisms?

Ethanol Signup and view all the answers

Which process generates ATP from glucose without oxygen?

Glycolysis Signup and view all the answers

What reaction is catalyzed by Alcohol Dehydrogenase?

Acetaldehyde to ethanol Signup and view all the answers

Which of the following is a product of glycolysis?

Pyruvate Signup and view all the answers

What is the ATP yield from the anaerobic catabolism of glucose?

2 ATP Signup and view all the answers

What process occurs in astrocytes surrounding neurons in the brain?

Fermentation of glucose to lactate Signup and view all the answers

Which cofactor is produced during the conversion of pyruvate to lactate?

NADH Signup and view all the answers

What distinguishes glucokinase from hexokinase in terms of glucose affinity?

Glucokinase is not inhibited by glucose-6-phosphate, unlike hexokinase. Signup and view all the answers

How does insulin affect glucokinase activity in the liver?

Insulin activates the gene that codes for glucokinase. Signup and view all the answers

What metabolic state does glucokinase primarily facilitate in the liver?

Glucose storage in the fed state. Signup and view all the answers

What type of conversion does Triose Phosphate Isomerase (TIM) catalyze?

Dihydroxyacetone-P to glyceraldehyde-3-P Signup and view all the answers

What factor regulates the activity of glucokinase in the liver?

The ratio of glucokinase to glucokinase regulatory protein. Signup and view all the answers

Which residue in Triose Phosphate Isomerase is primarily involved in acid/base catalysis?

Glutamate Signup and view all the answers

Which role does glucose-6-phosphatase serve in glucose metabolism?

Catalyzes the release of Pi from glucose-6-phosphate. Signup and view all the answers

What product is generated from glyceraldehyde-3-phosphate by Glyceraldehyde-3-phosphate Dehydrogenase?

1,3-bisphosphoglycerate Signup and view all the answers

Which intermediate is formed during the conversion of dihydroxyacetone phosphate to glyceraldehyde-3-phosphate?

Enediol Signup and view all the answers

What ion is required for the reaction catalyzed by Glyceraldehyde-3-phosphate Dehydrogenase?

NAD+ Signup and view all the answers

What structural change is involved in the aldose/ketose conversion mediated by TIM?

Acid/base catalysis Signup and view all the answers

Which of the following reactions is catalyzed by Aldolase?

Formation of fructose-1,6-bisphosphate from glyceraldehyde-3-phosphate Signup and view all the answers

Which molecule's concentration favors the formation of dihydroxyacetone-P?

Glyceraldehyde-3-phosphate Signup and view all the answers

Which enzyme facilitates the conversion of glyceraldehyde-3-phosphate and inorganic phosphate to 1,3-bisphosphoglycerate?

Glyceraldehyde-3-phosphate Dehydrogenase Signup and view all the answers

Which reaction mechanism is employed by Triose Phosphate Isomerase during its function?

Isomerization Signup and view all the answers

What is the primary function of Phosphoglycerate Mutase in the glycolytic pathway?

Catalyze the shift of a phosphate group from C3 to C2 Signup and view all the answers

Which ions are essential for the activity of Enolase?

Mg++ ions Signup and view all the answers

What type of reaction does Pyruvate Kinase catalyze?

Transfer of phosphate from PEP to ADP Signup and view all the answers

During the reaction catalyzed by Enolase, what is produced alongside phosphoenolpyruvate?

H2O Signup and view all the answers

What happens to the unstable enol formed from phosphoenolpyruvate in the action of Pyruvate Kinase?

It spontaneously converts to the keto form, pyruvate Signup and view all the answers

Which substrate is necessary for the reaction catalyzed by Pyruvate Kinase?

Phosphoenolpyruvate Signup and view all the answers

Which enzyme catalyzes the formation of 2-phosphoglycerate from 3-phosphoglycerate?

Phosphoglycerate Mutase Signup and view all the answers

What role do Mg++ ions play in the catalytic action of Enolase?

They stabilize the enolate intermediate Signup and view all the answers

Which of the following is a byproduct of the reaction catalyzed by Pyruvate Kinase?

ATP Signup and view all the answers

What is the relationship between the removal of Pi from PEP and the formation of pyruvate?

It triggers the enol to keto form conversion Signup and view all the answers

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.