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Gluconeogenesis - Meaning, Occurrence, Pathway and Glycolysis

Gluconeogenesis is a metabolic process where organisms synthesize sugars, notably glucose, from non-carbohydrate sources. NEET aspirants can find the detailed gluconeogenesis notes in the article below.
authorImageKrati Saraswat30 May, 2025
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Gluconeogenesis

Gluconeogenesis is a vital metabolic process in which organisms synthesize sugars, particularly glucose, from non-carbohydrate sources to fuel essential catabolic reactions. Glucose is the primary energy source for critical organs such as the testes, brain, erythrocytes, and kidney medulla, except during fasting periods when ketone bodies are utilized.

NEET Exam

This process primarily takes place in the liver and kidneys of mammals. It is important for sustaining life, as it provides an alternative means of producing glucose when the usual sources are unavailable. Eukaryotic organisms rely heavily on glucose for energy, and in the absence of dietary glucose, they can synthesize it from non-carbohydrate precursors through gluconeogenesis. Additionally, glucose can be derived from energy reserves like glycogen and starch. Gluconeogenesis pathway, its functions, occurrence, and more are provided in the article below.

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Gluconeogenesis Meaning

Carbohydrates are made up of sugar molecules, the most important of which is glucose, which has six carbon atoms. Maintaining a stable blood glucose level is essential because cells use it to generate energy, primarily adenosine triphosphate (ATP). Consuming carbohydrate-rich foods like pasta aids in maintaining this balance. The body uses gluconeogenesis to stabilise glucose levels between meals or fasting. Gluconeogenesis is the process by which cells make glucose from other macromolecules. This process is significant because glucose is the body's primary energy source. Glucose is the preferred substrate for cellular respiration, a metabolic process that converts glucose into ATP, the cell's energy currency. ATP is required to power many cellular functions, including material transport, cell division, and protein synthesis.

PROKARYOTIC CELLS

Gluconeogenesis Occurs In

Gluconeogenesis occurs in the liver, with some activity occurring in the kidneys. This metabolic process involves several key stages and occurs within specific compartments of cells:
1. Liver Cells (Hepatocytes):
  • Mitochondria: Pyruvate is converted into oxaloacetate.
  • Cytoplasm: Oxaloacetate is further converted into phosphoenolpyruvate (PEP), followed by additional gluconeogenic reactions.
2. Kidneys: Gluconeogenesis is less active in the kidneys compared to the liver. Gluconeogenesis is essential for regulating blood glucose levels during periods of fasting or when carbohydrate intake is low, as it converts non-carbohydrate substances such as amino acids and glycerol into glucose.

EUKARYOTIC CELLS

Gluconeogenesis Pathway

Gluconeogenesis is the process by which glucose is synthesized from non-carbohydrate precursors, primarily in the liver and to a lesser extent in the kidneys. It occurs when blood glucose levels are low, such as during fasting or intense exercise, and provides a crucial source of glucose for the body. The main substrates for gluconeogenesis are lactate, glycerol, and glucogenic amino acids. These substrates are converted into intermediates of the glycolytic pathway, which are then further metabolized to form glucose. Here is a step-by-step overview of the key reactions involved in gluconeogenesis:

1. Conversion of Pyruvate to Oxaloacetate:

Reaction: Pyruvate + CO2 + ATP ➡️ Oxaloacetate + ADP + Pi Enzyme: Pyruvate carboxylase Location: Mitochondria

2. Conversion of Oxaloacetate to Phosphoenolpyruvate (PEP):

Reaction: Oxaloacetate + GTP ➡️ PEP + CO2 + GDP Enzyme: Phosphoenolpyruvate carboxykinase (PEPCK) Location: Cytosol

3. Conversion of Fructose-1,6-bisphosphate to Fructose-6-phosphate:

Reaction: Fructose-1,6-bisphosphate + H2O ➡️ Fructose-6-phosphate + Pi Enzyme: Fructose-1,6-bisphosphatase Location: Cytosol

4. Conversion of Glucose-6-phosphate to Glucose:

Reaction: Glucose-6-phosphate + H2O ➡️ Glucose + Pi Enzyme: Glucose-6-phosphatase Location: Endoplasmic reticulum of liver cells Gluconeogenesis is a highly regulated process that ensures a steady supply of glucose, especially during fasting or low glucose availability. It involves several key enzymes and regulatory steps that allow glucose synthesis from non-carbohydrate precursors.

Gluconeogenesis From Propionate

Gluconeogenesis is an important metabolic pathway responsible for synthesizing glucose from non-carbohydrate sources. This process plays a vital role in regulating blood sugar levels, particularly during fasting or low-carbohydrate periods. In ruminant animals such as cattle, sheep, and goats, propionate serves as the primary substrate for gluconeogenesis. Propionate is a short-chain fatty acid produced through the fermentation of dietary fiber in the rumen, a specialized stomach compartment. The process of gluconeogenesis from propionate can be simplified into the following steps:
  1. Propionate uptake: Propionate is absorbed from the rumen and transported to the liver via the portal vein.
  2. Conversion to succinate: In the liver, propionate undergoes enzymatic reactions to form succinate.
  3. Entry into the citric acid cycle: Succinate enters the citric acid cycle (also known as the TCA cycle) in the mitochondria, producing intermediates that contribute to gluconeogenesis.
  4. Substrate formation: TCA cycle intermediates give rise to gluconeogenesis precursors like pyruvate and oxaloacetate.
  5. Glucose synthesis: Pyruvate and oxaloacetate are converted into glucose through enzyme-driven reactions in the liver cell cytoplasm.
  6. Glucose release: The newly synthesized glucose is released into the bloodstream to maintain stable blood sugar levels.

Importance of propionate-based gluconeogenesis in ruminants

  • Ruminants heavily depend on gluconeogenesis for glucose production due to their limited intake of dietary carbohydrates.
  • Propionate fermentation in the rumen provides a continuous energy source for gluconeogenesis, especially during periods of reduced feed intake.
  • This process ensures a consistent supply of glucose for crucial organs and tissues in ruminant animals.
In humans and non-ruminant animals:
  • Propionate is a minor gluconeogenic substrate compared to glucose, lactate, and amino acids.
  • It is derived from the breakdown of odd-chain and branched-chain fatty acids.
  • Its contribution to gluconeogenesis is relatively minor compared to ruminants.
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Gluconeogenesis and Glycolysis

Glycolysis and gluconeogenesis are crucial cellular processes that regulate the body's glucose levels. They are closely connected but function in opposite ways. Glycolysis is the breakdown of glucose, a six-carbon sugar, into pyruvate, a three-carbon molecule. This occurs in the cytoplasm of all cells and produces ATP (adenosine triphosphate), the cell's primary energy source. Gluconeogenesis , conversely, is the synthesis of glucose from non-carbohydrate sources such as lactate, pyruvate, glycerol, and specific amino acids. It mainly occurs in the liver and kidneys to maintain a steady glucose supply, especially during fasting or low-carbohydrate intake. Glycolysis supplies energy for most cellular activities, while gluconeogenesis maintains a consistent glucose supply for tissues that rely on it for energy, such as the brain and red blood cells. Proper regulation of these processes is vital for stable blood sugar levels and overall health.

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Gluconeogenesis and Glycogenolysis

Gluconeogenesis synthesises glucose from non-carbohydrate precursors, primarily in the liver and kidneys. This process is vital for maintaining blood glucose levels, especially during fasting or low dietary carbohydrate intake. Gluconeogenesis utilises substrates such as lactate, pyruvate, glycerol, and certain amino acids to generate glucose. Glycogenolysis is the breakdown of glycogen into glucose, predominantly occurring in the liver and muscles. This process serves as a rapid means of releasing glucose into the bloodstream during periods of low blood sugar or increased energy demand. Glycogenolysis is regulated by hormones such as glucagon and adrenaline, which stimulate its activity. It plays a crucial role in maintaining blood glucose levels and supporting metabolic processes that require glucose, particularly during physical activity or fasting. Physics Wallah offers online coaching for NEET Class 12 candidates. The courses are designed to meet the needs of Class 12 students and ensure thorough preparation for the test. PW provides high-quality study materials, live classes, PDF notes, and daily practice problems with video solutions in multiple languages to help students learn effectively.
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Gluconeogenesis FAQs

What is gluconeogenesis and its function?

Gluconeogenesis is a metabolic pathway that occurs in the liver and kidneys. Its primary function is to supply the body's plasma glucose needs between meals. This process is stimulated by diabetogenic hormones such as glucagon, growth hormone, epinephrine, and cortisol.

What is used in gluconeogenesis?

The major substrates used in gluconeogenesis are lactate, glycerol, and glucogenic amino acids. Glucogenic amino acids enter the gluconeogenesis pathway via the citric acid cycle.

What are the steps of gluconeogenesis?

The first step in gluconeogenesis is the conversion of pyruvate to phosphoenolpyruvic acid (PEP). This conversion requires several steps and enzymes, including pyruvate carboxylase, PEP carboxykinase, and malate dehydrogenase.

What is the formula for gluconeogenesis?

The overall equation for gluconeogenesis, starting from 2 cytosolic PEP molecules, is: 2 PEP + 4 H2O + 2 ATP + 2 NADH + 2 H → glucose + 2 ADP + 4 Pi + 2 NAD+.

Is gluconeogenesis a liver function?

Yes, gluconeogenesis is a liver function. In the fasted state, the liver secretes glucose through both glycogenolysis (breakdown of glycogen) and de novo glucose
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