Gluconeogenesis Overview
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Questions and Answers

What is the primary organ where gluconeogenesis occurs?

  • Spleen
  • Liver (correct)
  • Pancreas
  • Kidney

Which of the following substances can be a starting material for gluconeogenesis?

  • Fructose
  • Glucose
  • Glycogen
  • Lactic acid (correct)

Which enzyme is responsible for converting pyruvate to oxaloacetate in gluconeogenesis?

  • Hexokinase
  • Fructose 1,6-bisphosphatase
  • Pyruvate carboxylase (correct)
  • Phosphoenolpyruvate carboxykinase

Which of the following tissues primarily relies on glucose as an energy source?

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

Which of the following enzymes is NOT part of the gluconeogenesis pathway?

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

What is one of the key functions of gluconeogenesis in the body?

<p>To provide glucose during fasting (D)</p> Signup and view all the answers

In which cellular compartment does the conversion of phosphoenol pyruvate to oxaloacetate occur?

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

What role does lactic acid play in gluconeogenesis?

<p>Source of glucose (C)</p> Signup and view all the answers

What is the product of the conversion of fructose 1,6 biphosphate and water?

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

Which gluconeogenic substance is specifically mentioned to occur only in ruminants?

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

How many ATP molecules are consumed during the conversion of 2 molecules of pyruvate to glucose?

<p>6 ATP (C)</p> Signup and view all the answers

What role does glucagon play in gluconeogenesis?

<p>Stimulates gluconeogenesis by promoting enzyme synthesis (D)</p> Signup and view all the answers

What is the function of fructose 1,6 biphosphatase in gluconeogenesis?

<p>Converts fructose-1,6-bisphosphate to fructose-6-phosphate (B)</p> Signup and view all the answers

Which hormone is known to repress gluconeogenesis by affecting enzyme synthesis?

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

What is the final product formed from glycerol during gluconeogenesis?

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

What modification occurs to pyruvate kinase in response to glucagon?

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

Flashcards

Gluconeogenesis Definition

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

Gluconeogenesis Location (Organ)

Primarily in the liver (90%) and kidney (10%).

Gluconeogenesis Location (Cellular)

Occurs in both the cytoplasm and mitochondria.

Gluconeogenesis Importance (Fasting)

Provides glucose during fasting when glycogen stores are depleted, crucial for the brain and other tissues.

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Gluconeogenesis Importance (Energy)

Supplies energy to the body (nerves, RBCs, muscles) especially during exercise.

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Gluconeogenesis Importance (Other Uses)

Produces lactose (milk sugar) in mammary glands.

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Gluconeogenesis Waste Removal

Helps remove waste like lactic acid from the blood.

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Gluconeogenesis vs. Glycolysis (Key Difference)

Gluconeogenesis is mainly the reversal of glycolysis, but overcomes 3 irreversible steps using different enzymes.

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Pyruvate Carboxylase

Enzyme converting pyruvate to oxaloacetate in the mitochondria.

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Phosphoenolpyruvate Carboxykinase

Enzyme converting oxaloacetate to phosphoenolpyruvate in the cytoplasm.

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Glucose-6-phosphatase

Enzyme converting glucose-6-phosphate to free glucose, necessary to release glucose into the bloodstream.

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Fructose 1,6-biphosphatase

The enzyme responsible for converting fructose 1,6-biphosphate to fructose-6-phosphate during gluconeogenesis.

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Glucose-6-phosphatase

The enzyme that converts glucose-6-phosphate to glucose during gluconeogenesis.

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Gluconeogenic amino acids

Amino acids that can be converted to intermediates in gluconeogenesis.

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Pyruvate and lactate

These molecules can be converted to glucose via gluconeogenesis.

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Propionate

A gluconeogenic substance, primarily important in ruminants. It's converted into succinyl CoA.

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Glycerol

Derived from lipids; converted to dihydroxyacetone phosphate (DHAP) which enters the gluconeogenic pathway.

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Glycerol-3-phosphate

An intermediate in the conversion of glycerol to DHAP.

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Gluconeogenesis

The process of synthesizing glucose from non-carbohydrate precursors.

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Energy cost of gluconeogenesis

The energy required to synthesize a glucose molecule from 2 pyruvates: 6 ATPs and 2 NADHs.

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Pyruvate carboxylase

Key enzyme in gluconeogenesis, converting pyruvate to oxaloacetate.

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Phosphoenolpyruvate carboxykinase

Enzyme converting oxaloacetate to phosphoenolpyruvate, a crucial gluconeogenic step.

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Regulation of gluconeogenesis

Gluconeogenesis is regulated to prevent wasteful or redundant efforts with glycolysis.

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Glucocorticoids (e.g., cortisol)

Hormones that stimulate gluconeogenesis by inducing enzyme synthesis and increasing protein catabolism.

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Insulin

Hormone that inhibits gluconeogenesis by repressing key enzyme synthesis.

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Covalent modification

Hormones like glucagon and epinephrine regulate gluconeogenesis by phosphorylating enzymes, affecting their activity.

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Study Notes

Gluconeogenesis Definition

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

Gluconeogenesis Site

  • Primarily occurs in the liver (90%) and kidneys (10%)
  • Cellular site includes cytoplasm and mitochondria

Importance of Gluconeogenesis

  • Provides blood glucose during fasting (more than 18 hours) when glycogen stores are depleted
  • Only energy source for nervous tissue, RBCs, and skeletal muscles during exercise
  • Precursor of milk sugar (lactose) in mammary glands
  • Clears waste products like lactic acid from blood

Steps in Gluconeogenesis

  • Reverses glycolysis, excluding three irreversible steps
  • Overcomes these steps using different enzymes
    • Pyruvate kinase is replaced with pyruvate carboxylase (mitochondrial) and phosphoenolpyruvate carboxykinase
    • Phosphofructokinase-1 is replaced with fructose 1,6-bisphosphatase
    • Hexokinase/glucokinase is replaced with glucose-6-phosphatase

Conversion of Pyruvate to Phosphoenolpyruvate

  • Pyruvate, initially in the mitochondria, must be transported into the cytoplasm
  • Then:
    • Pyruvate carboxylase first converts pyruvate to oxaloacetate. (Requires CO2, ATP, Mn2+, biotin)
    • In the cytoplasm, oxaloacetate is converted to phosphoenolpyruvate by phosphoenolpyruvate carboxykinase (Requires GTP)

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

  • Achieved by the enzyme fructose 1,6-bisphosphatase

Conversion of Glucose-6-Phosphate to Glucose

  • Utilized by the enzyme glucose-6-phosphatase

Gluconeogenic Substances

  • Amino acids are key gluconeogenic substances
  • Pyruvate and lactate
  • Propionate (only in ruminants – converted to succinyl CoA)
  • Glycerol (derived from lipids, converted to glycerol-3-phosphate, then dihydroxyacetone phosphate, which then enters the common pathway)

Energy Cost of Gluconeogenesis

  • 6 ATP molecules and 2 NADH+H+ are required to convert 2 pyruvate molecules into glucose

Regulation of Gluconeogenesis

  • Gluconeogenesis and glycolysis are regulated to prevent simultaneous activation:
  • Key regulatory enzymes: pyruvate carboxylase, phosphoenolpyruvate carboxykinase, fructose 1,6-bisphosphatase, glucose-6-phosphatase
    • Regulated by changing enzyme synthesis rates or covalent modification, or allosteric regulation

Regulation - Changes in Enzyme Synthesis

  • Glucocorticoids (e.g., cortisol) stimulate gluconeogenesis by inducing key enzyme synthesis and increasing protein catabolism
  • Insulin inhibits gluconeogenesis by repressing key enzyme synthesis

Regulation - Covalent Modification

  • Glucagon and epinephrine stimulate gluconeogenesis by phosphorylating pyruvate kinase (inactivating it) and thus inhibiting glycolysis

Regulation - Allosteric Regulation

  • Acetyl CoA is an allosteric activator of pyruvate carboxylase, stimulating gluconeogenesis

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Gluconeogenesis Lecture 4 PDF

Description

This quiz covers the key aspects of gluconeogenesis, including its definition, sites of occurrence, importance, and the steps involved. Understand how glucose is synthesized from non-carbohydrate sources and learn the role of this process in maintaining blood glucose levels during fasting.

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