Biochemistry: Pyruvate Carboxylase Reaction

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Questions and Answers

Which statement accurately describes the role of glucagon and glucocorticoids in gluconeogenesis?

They have no effect on the transcription of the gluconeogenesis-related genes.

They decrease the transcription of the gene for fructose 1,6-bisphosphatase.

They increase the transcription of the gene for PEP-carboxykinase. (correct)

They inhibit the transcription of the gene for PEP-carboxykinase.

What is the consequence of a deficiency in glucose 6-phosphatase?

It causes liver necrosis due to excess glucose.

It results in severe fasting hypoglycemia. (correct)

It leads to prolonged hyperglycemia in fasting states.

It leads to increased production of fructose 2,6-bisphosphate.

Which of the following statements about the conversion of fructose 1,6-bisphosphate to fructose 6-phosphate is true?

It is weakened by elevated levels of ATP.

It is promoted by fructose 2,6-bisphosphate. (correct)

It is stimulated by increased amounts of AMP.

It is inhibited when ATP levels are high.

In which cellular location does gluconeogenesis primarily occur?

In the cytosol of liver cells. Signup and view all the answers

How does elevated AMP affect the enzyme fructose 1,6-bisphosphatase?

It inhibits the enzyme, thus decreasing gluconeogenesis. Signup and view all the answers

What is one of the primary functions of pyruvate carboxylase in liver and kidney cells?

Synthesis of glucose Signup and view all the answers

Which molecule acts as an allosteric activator of pyruvate carboxylase?

Acetyl CoA Signup and view all the answers

How is oxaloacetate transported from the mitochondria to the cytosol for gluconeogenesis?

As malate after reduction Signup and view all the answers

In muscle cells, what is the primary use of OAA produced by pyruvate carboxylase?

Replenishment of TCA cycle intermediates Signup and view all the answers

What is the consequence of low levels of acetyl CoA on pyruvate carboxylase activity?

It is largely inactive. Signup and view all the answers

Which enzyme is responsible for converting OAA to PEP in humans?

Phosphoenolpyruvate carboxykinase Signup and view all the answers

Which cofactor is required by pyruvate carboxylase and other carboxylases mentioned?

Biotin Signup and view all the answers

What must occur to OAA before it can be transported into the cytosol?

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

What effect do decreased levels of insulin have on gluconeogenesis?

Favor the mobilization of amino acids from muscle protein Signup and view all the answers

Which coenzymes are primarily provided by fatty acid catabolism for gluconeogenesis?

ATP and NADH Signup and view all the answers

What role does acetyl CoA play in gluconeogenesis during fasting?

Activates hepatic pyruvate carboxylase Signup and view all the answers

How does AMP affect the regulation of fructose 1,6-bisphosphatase?

Inhibits it to favor glycolysis Signup and view all the answers

Which of the following statements is true regarding gluconeogenic precursors?

Glucogenic amino acids are a primary source of gluconeogenic precursors Signup and view all the answers

Which enzymes are responsible for the irreversible reactions in gluconeogenesis?

Pyruvate kinase, hexokinase, and phosphofructokinase Signup and view all the answers

Which product of pyruvate carboxylase is crucial for the gluconeogenesis pathway?

Phosphoenolpyruvate (PEP) Signup and view all the answers

Which organs are capable of releasing free glucose from glucose 6-phosphate?

Liver and kidney Signup and view all the answers

What happens to acetyl CoA during fasting conditions?

It accumulates and promotes gluconeogenesis Signup and view all the answers

What regulatory mechanism is shared between glycolysis and gluconeogenesis?

Inhibition of fructose 1,6-bisphosphatase leads to activation of PFK-1 Signup and view all the answers

What role does glucose 6-phosphatase play in glucose metabolism?

It converts glucose 6-phosphate to free glucose Signup and view all the answers

What characterizes Type Ia glycogen storage disease?

Deficiency in glucose 6-phosphatase Signup and view all the answers

How many irreversible reactions do glycolysis and gluconeogenesis share?

Three Signup and view all the answers

Which enzymes are involved in circumventing the irreversible steps of glycolysis during gluconeogenesis?

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

What is the main function of glucose 6-phosphate translocase?

To transport glucose 6-phosphate across the ER membrane Signup and view all the answers

What does high glucose 6-phosphate level indicate about gluconeogenesis?

It is inhibited Signup and view all the answers

What is the role of lactate in the Cori cycle?

It is taken up by the liver to be reconverted to glucose. Signup and view all the answers

Which of these statements about glucose transporters (GLUTs) is correct?

GLUTs facilitate the movement of glucose into blood Signup and view all the answers

During fasting, what primarily provides glucose to the body?

Amino acids from tissue protein hydrolysis Signup and view all the answers

Which of the following is true about the conversion of pyruvate to glucose?

It involves pyruvate carboxylase and PEP-carboxykinase. Signup and view all the answers

What happens to the equilibrium of reversible reactions of glycolysis during gluconeogenesis?

It favors glucose synthesis Signup and view all the answers

Which of the following is a characteristic of gluconeogenesis?

It requires energy input Signup and view all the answers

What is one of the irreversible reactions in glycolysis that must be circumvented in gluconeogenesis?

Conversion of PEP to pyruvate by pyruvate kinase Signup and view all the answers

Which compounds cannot contribute to a net synthesis of glucose?

Acetyl CoA Signup and view all the answers

What coenzyme is required for the enzyme pyruvate carboxylase?

Biotin Signup and view all the answers

What is the product formed when pyruvate undergoes carboxylation?

Oxaloacetate Signup and view all the answers

Which of the following statements is correct concerning α-keto acids?

They can enter the TCA cycle and form oxaloacetate. Signup and view all the answers

What is the primary function of the transport protein in the Cori cycle?

Facilitates lactate diffusion across membranes. Signup and view all the answers

Which amino acids cannot yield glucose due to the pyruvate dehydrogenase reaction?

Leucine and lysine Signup and view all the answers

How does glucagon influence the activity of fructose 1,6-bisphosphatase in gluconeogenesis?

It lowers the level of fructose 2,6-bisphosphate, activating fructose 1,6-bisphosphatase. Signup and view all the answers

What is the primary effect of covalent modification of pyruvate kinase due to glucagon signaling?

Inactivation of pyruvate kinase, diverting PEP towards glucose synthesis. Signup and view all the answers

Which substrate is crucial for gluconeogenesis during fasting, particularly for providing carbon skeletons?

Glucogenic amino acids Signup and view all the answers

What role does acetyl CoA play in the regulation of pyruvate carboxylase during fasting?

Enhances the allosteric activity of pyruvate carboxylase. Signup and view all the answers

Which process is a result of glucagon promoting the transcription of the gene for PEP-carboxykinase?

Increased availability of the PEP-carboxykinase enzyme. Signup and view all the answers

What primarily provides the necessary coenzymes ATP and NADH for gluconeogenesis?

Beta-oxidation of fatty acids. Signup and view all the answers

Which mechanism is responsible for the decrease in gluconeogenesis when insulin levels are high?

Inhibition of fructose 1,6-bisphosphatase activity. Signup and view all the answers

What is the outcome of glucoagon-induced activation of PEP-carboxykinase on gluconeogenesis?

It enhances the conversion of oxaloacetate to phosphoenolpyruvate. Signup and view all the answers

What is the effect of decreasing levels of fructose 2,6-bisphosphate in gluconeogenesis regulation?

Activation of gluconeogenesis. Signup and view all the answers

What indicates a high level of acetyl CoA during fasting in liver cells?

Enhanced gluconeogenesis through pyruvate carboxylase activation. Signup and view all the answers

What is the primary clinical consequence of a deficiency in glucose 6-phosphatase?

Severe fasting hypoglycemia Signup and view all the answers

Which substrate is essential for the activity of pyruvate carboxylase, an important enzyme in gluconeogenesis?

Biotin Signup and view all the answers

What effect does a decrease in the insulin-to-glucagon ratio have on gluconeogenesis?

It stimulates gluconeogenesis. Signup and view all the answers

Which reaction is unique to the gluconeogenesis pathway?

Oxaloacetate to phosphoenolpyruvate Signup and view all the answers

Which enzyme activity is inhibited by excessive levels of avidin?

Pyruvate carboxylase Signup and view all the answers

What is the primary effect of elevated levels of acetyl CoA in the liver?

Diverting pyruvate towards gluconeogenesis Signup and view all the answers

Which allosteric regulator inhibits fructose 1,6-bisphosphatase?

Fructose 2,6-bisphosphate Signup and view all the answers

During fasting, which metabolic pathway helps maintain blood glucose levels primarily?

Gluconeogenesis Signup and view all the answers

How does fructose 2,6-bisphosphate influence metabolic pathways?

It activates glycolysis while inhibiting gluconeogenesis Signup and view all the answers

How does high AMP concentration affect gluconeogenesis?

Inhibits gluconeogenesis Signup and view all the answers

What role does pyruvate carboxylase play in gluconeogenesis?

Facilitates the conversion of pyruvate to oxaloacetate Signup and view all the answers

In which cellular compartment does gluconeogenesis primarily take place?

Cytosol Signup and view all the answers

Which of the following statements is accurate regarding gluconeogenesis?

It requires ATP and GTP. Signup and view all the answers

What triggers the transcription of PEP-carboxykinase gene?

Increased levels of glucagon Signup and view all the answers

Which process is directly inhibited by elevated levels of pyruvate dehydrogenase complex activity?

Gluconeogenesis Signup and view all the answers

Which substrate cannot be converted into glucose through gluconeogenesis?

Acetyl CoA Signup and view all the answers

What metabolic state primarily contributes to the accumulation of acetyl CoA in the liver?

Fasting state Signup and view all the answers

Which enzyme's activity is specifically downregulated by high AMP levels?

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

What type of molecule is primarily transformed into glucose via gluconeogenesis?

Lactate Signup and view all the answers

Which metabolic pathway is enhanced when energy needs increase and AMP levels rise?

Glycolysis Signup and view all the answers

What is the effect of adenosine monophosphate (AMP) on gluconeogenesis?

It inhibits gluconeogenesis by inhibiting fructose 1,6-bisphosphatase. Signup and view all the answers

How does the increase in NADH affect oxaloacetate availability during ethanol metabolism?

It decreases oxaloacetate availability due to the reverse reaction driven by NADH. Signup and view all the answers

What role does acetyl coenzyme A play in the regulation of gluconeogenesis?

It activates pyruvate carboxylase, facilitating gluconeogenesis. Signup and view all the answers

Which molecule is responsible for reciprocal regulation of glycolysis and gluconeogenesis?

Fructose 2,6-bisphosphate Signup and view all the answers

What happens to gluconeogenesis when ethanol is metabolized?

Gluconeogenesis is suppressed due to reduced substrates like oxaloacetate. Signup and view all the answers

What is the primary effect of fructose 2,6-bisphosphate on glycolysis and gluconeogenesis?

It solely enhances glycolysis at the expense of gluconeogenesis. Signup and view all the answers

How does an increase in lactic acid affect gluconeogenesis?

It decreases the availability of pyruvate for gluconeogenesis. Signup and view all the answers

What is the main effect of fatty acid oxidation on gluconeogenesis?

It activates pyruvate carboxylase, supporting gluconeogenesis. Signup and view all the answers

Which condition is likely to augment gluconeogenesis?

Reduced NADH concentration Signup and view all the answers

Study Notes

Pyruvate Carboxylase Reaction

Occurs in mitochondria of liver and kidney cells, providing substrate for gluconeogenesis and replenishing TCA cycle intermediates.
Muscle cells utilize pyruvate carboxylase only for replenishment (anaplerotic) and do not synthesize glucose.
Requires biotin, a coenzyme, for function and is activated by acetyl CoA.

Allosteric Regulation of Pyruvate Carboxylase

Activated by elevated acetyl CoA levels, signaling increased OAA synthesis required during fasting.
Pyruvate is primarily oxidized by the PDH complex when acetyl CoA is low.

Transport of Oxaloacetate

OAA must be converted to PEP to continue gluconeogenesis; this conversion occurs both in mitochondria and cytosol.
OAA cannot cross the mitochondrial membrane; converted to malate for transport.
Malate is reoxidized to OAA in the cytosol by cytosolic malate dehydrogenase.

Lactate Production and the Cori Cycle

Exercising muscle and cells without mitochondria (like RBCs) release lactate into the bloodstream.
Lactate is converted back to glucose in the liver, completing the Cori cycle.

Role of Amino Acids

Glucogenic amino acids contribute to glucose production during fasting by generating α-keto acids.
α-Keto acids can enter the TCA cycle to form OAA, leading to glucose synthesis.

Unique Reactions in Gluconeogenesis

Three irreversible glycolytic reactions must be bypassed in gluconeogenesis: catalyzed by pyruvate kinase, PFK-1, and hexokinase.
Pyruvate carboxylase converts pyruvate to OAA, which is then converted to PEP by PEP carboxykinase.

Biotin and Enzyme Regulation

Biotin is covalently bound to pyruvate carboxylase and is necessary for its activity.
The hydrolysis of ATP forms an enzyme–biotin–CO2 intermediate that aids in carboxylating pyruvate.

Dephosphorylation of Glucose 6-Phosphate

Glucose 6-phosphatase hydrolyzes glucose 6-phosphate, allowing free glucose release from liver and kidney cells.
This process relies on a complex of glucose 6-phosphate translocase and glucose 6-phosphatase.

Summary of Gluconeogenesis Pathways

11 reactions convert pyruvate to free glucose, with 7 being reversible glycolytic reactions.
Gluconeogenesis is influenced by substrate availability, particularly glucogenic amino acids.

Energy State and Pathway Regulation

Fasting increases pyruvate carboxylase activity via acetyl CoA accumulation due to lipolysis.
Fructose 1,6-bisphosphatase is inhibited by AMP and activated by ATP, providing reciprocal regulation with glycolysis.

Importance of Gluconeogenesis

Maintains blood glucose levels during fasting when glycogen stores are depleted.
Relies on mitochondrial and cytosolic enzymes and progresses only with sufficient glucogenic precursors, ATP, and NADH.

Regulation of Gluconeogenesis

Gluconeogenesis is regulated by circulating glucagon levels and substrate availability.
Slow adaptive changes in enzyme activity occur due to altered rates of enzyme synthesis or degradation.

Role of Glucagon

Glucagon is a peptide hormone from pancreatic alpha cells that stimulates gluconeogenesis.
It decreases fructose 2,6-bisphosphate levels, activating fructose 1,6-bisphosphatase and inhibiting PFK-1, promoting gluconeogenesis over glycolysis.
Binds to G protein–coupled receptors, elevating cAMP and stimulating inactivation of hepatic pyruvate kinase, thus diverting PEP to glucose synthesis.
Increases transcription of the PEP-carboxykinase gene, enhancing enzyme availability during fasting.

Substrate Availability

Increased availability of gluconeogenic precursors, especially glucogenic amino acids, boosts glucose production.
Decreased insulin levels lead to amino acid mobilization from muscle for gluconeogenesis.
Fatty acid catabolism supplies ATP and NADH required for the process.

Allosteric Regulation

Acetyl CoA activates hepatic pyruvate carboxylase during fasting, directing pyruvate towards gluconeogenesis instead of the TCA cycle.
Fructose 1,6-bisphosphatase is inhibited by AMP, which activates PFK-1, balancing glycolysis and gluconeogenesis.

Gluconeogenic Precursors

Precursors include glycolytic and TCA cycle intermediates, glycerol from triacylglycerol hydrolysis, lactate, and α-keto acids from glucogenic amino acids.
Seven glycolytic reactions are reversible and utilized in gluconeogenesis; three irreversible steps must be bypassed.

Key Enzymes in Gluconeogenesis

Pyruvate carboxylase converts pyruvate to oxaloacetate, requiring biotin and ATP, and is activated by acetyl CoA.
PEP-carboxykinase synthesizes PEP from oxaloacetate, requiring GTP, with increased gene transcription by glucagon and glucocorticoids, and decreased by insulin.
Fructose 1,6-bisphosphate is converted to fructose 6-phosphate by fructose 1,6-bisphosphatase, which is activated by ATP and inhibited by AMP and fructose 2,6-bisphosphate.

Key Concepts about Ethanol Metabolism

Ethanol metabolism by alcohol dehydrogenase increases NADH, decreasing the NAD+/NADH ratio.
This shift inhibits gluconeogenesis by reducing the availability of oxaloacetate, as malate oxidation to oxaloacetate is reversed due to high NADH levels.
Increased NADH also drives the conversion of pyruvate to lactate, reducing substrates available for gluconeogenesis.

Role of Acetyl CoA

Acetyl CoA produced from fatty acid oxidation cannot be converted to glucose.
It inhibits the pyruvate dehydrogenase complex and activates pyruvate carboxylase, directing pyruvate towards gluconeogenesis.

Final Steps in Gluconeogenesis

Glucose 6-phosphate is converted to glucose by glucose 6-phosphatase, essential for gluconeogenesis and glycogen degradation.
Deficiency of glucose 6-phosphatase leads to severe fasting hypoglycemia.

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Description

Explore the role of pyruvate carboxylase in gluconeogenesis and the TCA cycle. This quiz focuses on its function in liver, kidney, and muscle cells, highlighting the biochemical pathways involved. Test your knowledge on this essential enzymatic reaction and its implications in cellular metabolism.