Gluconeogenesis Overview and Importance

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Questions and Answers

What is the primary purpose of gluconeogenesis?

  • To break down glycogen into glucose
  • To synthesize glucose from non-carbohydrate sources (correct)
  • To transport glucose to the brain
  • To convert glucose into lactic acid

Which enzyme is responsible for the conversion of pyruvate to oxaloacetate in gluconeogenesis?

  • Fructose 1,6-bisphosphatase
  • Malate dehydrogenase
  • Pyruvate carboxylase (correct)
  • Phosphoenol pyruvate carboxykinase

During fasting, where does the majority of gluconeogenesis occur in the body?

  • In the skin
  • In the lungs
  • In the heart
  • In the liver (correct)

Which of the following is NOT a substrate for gluconeogenesis?

<p>Fructose (A)</p> Signup and view all the answers

Which step in gluconeogenesis is specifically catalyzed by fructose 1,6-bisphosphatase?

<p>Dephosphorylation of fructose 1,6-bisphosphate (C)</p> Signup and view all the answers

What is the cellular location where oxidative decarboxylation of pyruvate to oxaloacetate occurs?

<p>Mitochondria (C)</p> Signup and view all the answers

Which of the following statements about gluconeogenesis is false?

<p>It uses the same enzymes as glycolysis throughout. (B)</p> Signup and view all the answers

What is the initial molecule that enters gluconeogenesis after being transported to the mitochondria?

<p>Pyruvate (D)</p> Signup and view all the answers

What is the main substance that is converted into glucose-6-phosphate during gluconeogenesis?

<p>Fructose 1,6-bisphosphate (A)</p> Signup and view all the answers

Which enzyme is primarily responsible for converting pyruvate into oxaloacetate?

<p>Pyruvate carboxylase (C)</p> Signup and view all the answers

What is the energy cost associated with converting 2 molecules of pyruvate to glucose?

<p>6 ATP and 2 NADH+H+ (C)</p> Signup and view all the answers

Which regulatory hormone stimulates gluconeogenesis by inducing the synthesis of key enzymes?

<p>Cortisol (B)</p> Signup and view all the answers

Which of the following substances is NOT considered a gluconeogenic precursor?

<p>Fructose-6-phosphate (D)</p> Signup and view all the answers

What effect does insulin have on gluconeogenesis?

<p>It inhibits gluconeogenesis. (D)</p> Signup and view all the answers

During gluconeogenesis, what is glycerol converted into before entering the common pathway?

<p>Dihydroxy acetone phosphate (D)</p> Signup and view all the answers

What is the role of glucagon in the regulation of gluconeogenesis?

<p>It stimulates gluconeogenesis by promoting enzyme phosphorylation. (B)</p> Signup and view all the answers

Flashcards

What is gluconeogenesis?

The synthesis of glucose or glycogen from non-carbohydrate sources, such as lactic acid, pyruvate, glycerol, amino acids, and propionic acid.

Where does gluconeogenesis mainly occur?

The liver is the primary site of gluconeogenesis, responsible for about 90% of its production. The kidney also plays a role, producing about 10%.

What is the importance of gluconeogenesis?

Gluconeogenesis is crucial during fasting or starvation when glycogen stores are depleted. It ensures a continuous supply of glucose.

How does gluconeogenesis maintain blood glucose levels?

Gluconeogenesis helps maintain blood glucose levels during prolonged fasting, providing energy for tissues like the brain and red blood cells.

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How does gluconeogenesis contribute to waste removal?

Gluconeogenesis is vital for clearing metabolic waste products like lactic acid, produced by muscle during exercise.

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How does gluconeogenesis differ from glycolysis?

Gluconeogenesis bypasses three irreversible steps in glycolysis, using different enzymes to achieve the reverse reaction.

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Which enzymes are crucial for the pyruvate to phosphoenol pyruvate conversion in gluconeogenesis?

Pyruvate carboxylase (mitochondrial) and phosphoenol pyruvate carboxykinase (cytoplasm) are the two key enzymes that work together to convert pyruvate to phosphoenol pyruvate.

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Describe the process of converting pyruvate to phosphoenol pyruvate.

The conversion of pyruvate to phosphoenol pyruvate involves a series of steps, moving between the mitochondria and cytoplasm, with different enzymes playing roles.

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Fructose 1,6-bisphosphatase

Fructose 1,6-bisphosphatase catalyzes the hydrolysis of fructose 1,6-bisphosphate, releasing inorganic phosphate and converting it to fructose-6-phosphate.

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Glucose-6-phosphatase

Glucose-6-phosphatase removes a phosphate group from glucose-6-phosphate, resulting in the formation of glucose and inorganic phosphate. This enzyme is primarily found in the liver and kidneys.

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Gluconeogenic Amino Acids

Gluconeogenic amino acids are amino acids that can be converted into glucose through gluconeogenesis. They serve as a source of carbon skeletons for glucose synthesis. Examples include alanine, glutamine, and asparagine.

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Propionate role in Gluconeogenesis

Propionic acid is a three-carbon fatty acid converted to succinyl CoA, a key intermediate in the citric acid cycle, contributing to gluconeogenesis. This process is particularly relevant in ruminants due to their unique digestive system.

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Glycerol and Gluconeogenesis

Glycerol, derived from lipids of adipose tissue, can contribute to gluconeogenesis through its conversion to dihydroxyacetone phosphate, a key intermediate of glycolysis.

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Energy Cost of Gluconeogenesis

Gluconeogenesis requires a significant energy expenditure in order to convert pyruvate to glucose. This process consumes 6 ATP molecules and 2 NADH+ H+ per two molecules of pyruvate converted.

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Regulation of Gluconeogenesis

Gluconeogenesis and glycolysis are tightly regulated processes that occur in a coordinated manner. Regulating enzymes include pyruvate carboxylase, phosphoenol pyruvate carboxykinase, fructose 1,6-bisphosphatase, and glucose-6-phosphatase, ensuring proper balance between glucose production and consumption.

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Study Notes

Gluconeogenesis Definition

  • Gluconeogenesis is the synthesis of glucose or glycogen from non-carbohydrate sources
  • These sources include lactic acid, pyruvic acid, propionic acid, glycerol, and amino acids

Gluconeogenesis Site

  • Organ site: 90% in the liver and 10% in the kidney
  • Cellular site: cytoplasm and mitochondria

Importance of Gluconeogenesis

  • Provides blood with glucose during fasting (more than 18 hours) when glycogen stores are depleted
  • The only source of energy for nervous tissue, red blood cells (RBCs), and skeletal muscles during exercise.
  • Precursor for milk sugar (lactose) in mammary gland
  • Clears the blood of waste products like lactic acid produced in skeletal muscles and RBCs

Gluconeogenesis Steps

  • Primarily the reversal of glycolysis, except for 3 irreversible kinases.
  • These irreversible kinases are bypassed by specific enzymes.
  • Key enzymes involved in gluconeogenesis include:
    • Pyruvate carboxylase (mitochondrial)
    • Phosphoenolpyruvate carboxykinase
    • Fructose 1,6-bisphosphatase
    • Glucose-6-phosphatase

Conversion of Pyruvate to Phosphoenolpyruvate

  • Pyruvate must be transported from the mitochondria to the cytoplasm.
  • The process involves Pyruvate carboxylase and Phosphoenolpyruvate carboxykinase
  • Pyruvate → Oxaloacetate → Malate → Oxaloacetate → phosphoenolpyruvate

Conversion of Fructose 1,6-Bisphosphate to Fructose-6-Phosphate

  • Catalyzed by Fructose 1,6-bisphosphatase

Conversion of Glucose-6-Phosphate to Glucose

  • Catalyzed by Glucose-6-phosphatase

Gluconeogenic Substances

  • Gluconeogenic amino acids
  • Pyruvate and lactate
  • Propionate (occurs only in ruminants)
    • Propionic acid is converted to succinyl CoA
  • Glycerol
    • Derived from lipids in adipose tissue during fasting
    • Converted to glycerol-3-phosphate and then dihydroxyacetone phosphate.

Energy Cost of Gluconeogenesis

  • Converting 2 molecules of pyruvate to glucose requires:
    • 6 ATP molecules
    • 2 NADH+H+

Regulation of Gluconeogenesis

  • Gluconeogenesis and glycolysis are coordinated. When one is active, the other is inhibited
  • Key regulatory enzymes: pyruvate carboxylase, phosphoenolpyruvate carboxykinase, fructose-1,6-bisphosphatase, and glucose-6-phosphatase
  • These enzymes are regulated by changes in enzyme synthesis, covalent modification, and allosteric regulation.

Regulation of Enzyme Synthesis

  • Glucocorticoids (cortisol) stimulate gluconeogenesis
    • Increase synthesis of key gluconeogenesis enzymes
    • Increase protein catabolism to provide amino acids
  • Insulin inhibits gluconeogenesis by suppressing enzyme synthesis

Covalent Modification

  • Glucagon and epinephrine stimulate gluconeogenesis by phosphorylating/activating key enzymes like pyruvate kinase (making it inactive hence inhibiting glycolysis)
  • This inhibits glycolysis and stimulates gluconeogenesis

Allosteric Regulation

  • Acetyl CoA is an allosteric activator of pyruvate carboxylase.
  • Derived from fatty acid (FA) oxidation
  • Stimulates gluconeogenesis by providing Acetyl CoA which activates pyruvate carboxylase.
  • Also needs ATP for pyruvate carboxylase and phosphoenol pyruvate carboxykinase.

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