Gluconeogenesis Overview

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Questions and Answers

Which of the following is NOT a source for gluconeogenesis?

  • Amino acids
  • Fatty acids (correct)
  • Glycerol
  • Lactic acid

What percentage of gluconeogenesis occurs in the liver?

  • 10%
  • 50%
  • 90% (correct)
  • 75%

Why is gluconeogenesis important during prolonged fasting?

  • It converts glucose into fatty acids.
  • It supplies glucose to the brain and red blood cells. (correct)
  • It decreases blood sugar levels for better metabolism.
  • It synthesizes amino acids for muscle repair.

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

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

Which of the following hormones is likely to stimulate gluconeogenesis?

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

Which process does NOT describe gluconeogenesis?

<p>Conversion of glucose to glycogen (A)</p> Signup and view all the answers

What role does malate dehydrogenase play in gluconeogenesis?

<p>It converts oxaloacetate to malate. (D)</p> Signup and view all the answers

Which enzyme in gluconeogenesis counteracts hexokinase in glycolysis?

<p>Glucose-6-phosphatase (A)</p> Signup and view all the answers

Which enzyme is responsible for the conversion of fructose 1,6 biphosphate to fructose-6-phosphate?

<p>Fructose 1,6 biphosphatase (C)</p> Signup and view all the answers

What is the main energy substrate consumed for converting 2 molecules of pyruvate to glucose?

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

Which of the following is NOT a gluconeogenic substance?

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

What effect does insulin have on gluconeogenesis?

<p>Inhibits gluconeogenesis by repressing enzyme synthesis (C)</p> Signup and view all the answers

Which enzyme is activated by glucagon and epinephrine to stimulate gluconeogenesis?

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

Which pathway is inhibited when gluconeogenesis is active?

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

Which compound is derived from lipids during fasting and is involved in gluconeogenesis?

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

What stimulates gluconeogenesis by inducing the synthesis of key enzymes?

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

Flashcards

Gluconeogenesis

The process of synthesizing glucose from non-carbohydrate sources like lactate, pyruvate, glycerol, and amino acids.

Liver

The main site for gluconeogenesis, responsible for making around 90% of the body's glucose.

Pyruvate to PEP conversion

The process of converting pyruvate to phosphoenolpyruvate (PEP), a key step in gluconeogenesis.

Pyruvate carboxylase

An enzyme that catalyzes the conversion of pyruvate to oxaloacetate in the mitochondria, utilizing carbon dioxide.

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Phosphoenolpyruvate carboxykinase (PEPCK)

An enzyme that catalyzes the conversion of oxaloacetate to PEP in the cytoplasm, using GTP as an energy source.

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Why is gluconeogenesis important?

The purpose of gluconeogenesis during extended fasting.

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What does gluconeogenesis provide?

Gluconeogenesis ensures that essential tissues like the brain and red blood cells have a constant supply of glucose, even during prolonged fasting.

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How does gluconeogenesis help the body?

Gluconeogenesis helps clear waste products like lactic acid from the blood, maintaining tissue function.

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Fructose 1,6-bisphosphatase

An enzyme that converts fructose 1,6-bisphosphate into fructose-6-phosphate, releasing inorganic phosphate (Pi) and water (H2O). This is a crucial step in gluconeogenesis.

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Gluconeogenic Amino Acids

Amino acids that can be used as precursors for glucose synthesis in gluconeogenesis.

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Phosphoenolpyruvate Carboxykinase

An enzyme that converts oxaloacetate to phosphoenolpyruvate, consuming GTP. This is another crucial step in gluconeogenesis, bypassing a key irreversible reaction in glycolysis.

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Glucose 6-Phosphatase

An enzyme that converts glucose 6-phosphate to glucose, releasing inorganic phosphate. This is a crucial step in gluconeogenesis, allowing glucose to be released from the liver into the bloodstream.

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Glucocorticoids (e.g. Cortisol)

A hormone that stimulates gluconeogenesis by inducing the synthesis of key gluconeogenic enzymes and increasing protein catabolism, leading to an increase in gluconeogenic amino acids.

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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

  • The primary site is the liver (90%) and the kidney (10%)
  • Gluconeogenesis occurs in both the cytoplasm and mitochondria

Gluconeogenesis Importance

  • Provides blood glucose during fasting periods (more than 18 hours) when glycogen stores are depleted
  • Is the sole energy source for nervous tissue, red blood cells (RBCs), and skeletal muscle during exercise.
  • Is a precursor for milk sugar (lactose) in mammary glands
  • Clears waste products from the blood, such as lactic acid produced in skeletal muscles and RBCs

Gluconeogenesis Steps

  • Gluconeogenesis is mainly the reversal of glycolysis, except for three irreversible kinases
  • These irreversible steps are overcome by specific enzymes
  • Enzymes of glycolysis include: Pyruvate kinase, Phosphofructokinase-1, Hexokinase & glucokinase
  • Enzymes of gluconeogenesis include:
    • Pyruvate carboxylase (mitochondrial), Phosphoenol pyruvate carboxykinase
    • Fructose 1,6 biphosphatase
    • Glucose-6-phosphatase

Gluconeogenesis Substrates

  • Gluconeogenic amino acids - critical nitrogen and carbon sources
  • Pyruvate and Lactate
  • Propionate
    • Propionic acid is converted to succinyl CoA only in ruminants
  • Glycerol
    • Derived from lipids in adipose tissue during fasting
    • Converted to glycerol-3-phosphate, then dihydroxyacetone phosphate

Energy Cost

  • Converting 2 pyruvate molecules to glucose consumes 6 ATP molecules and 2 NADH+ H+

Gluconeogenesis Regulation

  • Gluconeogenesis and glycolysis are coordinated pathways. If one is active, the other should be inhibited
  • Key regulatory enzymes include:
    • Pyruvate carboxylase
    • Phosphoenol pyruvate carboxykinase
    • Fructose 1,6-biphosphatase
    • Glucose-6-phosphatase
  • Regulation occurs through:
    • Changes in enzyme synthesis
      • Glucocorticoids (e.g., cortisol) stimulate gluconeogenesis by inducing enzyme synthesis, and increase protein catabolism to provide gluconeogenic amino acids.
      • Insulin inhibits gluconeogenesis by reducing enzyme synthesis
    • Covalent modification
      • Glucagon and epinephrine stimulate gluconeogenesis by phosphorylating pyruvate kinase, inhibiting glycolysis, and stimulating gluconeogenesis.
    • Allosteric regulation
      • Acetyl-CoA is an allosteric activator of pyruvate carboxylase. Derived from fat oxidation, high levels indicate increased gluconeogenesis.
      • Fructose-2,6-bisphosphate (a glycolysis regulator) is relevant in gluconeogenesis regulation

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