Which of the following is not used for the production of glucose?

December 22, 2025 •

4 min read

Over 90% of all gluconeogenesis (glucose production from non-carbohydrate sources) in humans comes from lactate, glycerol, and glucogenic amino acids. In contrast, a common misconception exists regarding which specific molecules the human body can and cannot convert into usable glucose. This article clarifies this metabolic distinction by identifying the primary exception and explaining the underlying biochemical reasons.

Quick Summary

This article examines the metabolic pathways for glucose production, revealing that even-chain fatty acids cannot be converted to glucose in humans, despite the use of other precursors like lactate, glycerol, and amino acids.

Key Points

Even-chain fatty acids are not used for glucose production: Unlike plants and other organisms, humans cannot convert the acetyl-CoA derived from typical fatty acid breakdown into glucose.
The pyruvate dehydrogenase reaction is irreversible: This metabolic step is the point of no return, preventing acetyl-CoA from being converted back into pyruvate, which is a key substrate for gluconeogenesis.
Glycerol, lactate, and amino acids can be converted to glucose: The body uses precursors like glycerol (from fat breakdown), lactate (from anaerobic exercise), and glucogenic amino acids (from protein) to synthesize new glucose.
Ketone bodies are an alternative fuel, not glucose: During periods of low carbohydrate availability, the liver produces ketone bodies from acetyl-CoA to provide an energy source for the brain and other tissues, but this is a separate pathway from glucose production.
Glycogenolysis is distinct from gluconeogenesis: While glycogen is a stored form of glucose that can be broken down for energy, gluconeogenesis is the creation of new glucose from non-carbohydrate sources.

The question, "Which of the following is not used for the production of glucose?", has a specific answer rooted in fundamental biochemistry. While various metabolic processes can generate glucose, not all nutrient sources can be converted. The primary exception in humans is the typical even-chain fatty acid.

The Irreversible Metabolic Barrier: Acetyl-CoA

The reason even-chain fatty acids cannot be converted to glucose in humans lies in an irreversible step within the metabolic pathway. During the breakdown of fats (triglycerides), fatty acids are processed through a series of reactions known as beta-oxidation. This process breaks down the fatty acid chains into two-carbon units of acetyl-CoA. Once acetyl-CoA is formed, it enters the citric acid (Krebs) cycle.

However, the step that converts pyruvate into acetyl-CoA via the enzyme pyruvate dehydrogenase is irreversible in humans. This means the body cannot convert acetyl-CoA back into pyruvate, a crucial starting material for gluconeogenesis, the process of synthesizing new glucose. While the carbons from acetyl-CoA are eventually released as carbon dioxide in the citric acid cycle, there is no net production of new carbon skeletons for glucose synthesis.

Sources the Body CAN Use for Glucose Production

In contrast to even-chain fatty acids, the body can use several other non-carbohydrate precursors to produce glucose, primarily during periods of fasting, starvation, or intense exercise when carbohydrate intake is low.

Lactate

Produced by anaerobic glycolysis in red blood cells and exercising muscles, lactate can be transported to the liver. There, it is converted back to pyruvate, which can then enter the gluconeogenesis pathway to be turned into glucose. This recycling of glucose and lactate is known as the Cori cycle.

Glycerol

This three-carbon molecule is released from the breakdown of triglycerides (fats) in adipose tissue through a process called lipolysis. Unlike fatty acids, glycerol can enter the gluconeogenesis pathway in the liver by being converted into an intermediate called dihydroxyacetone phosphate (DHAP). This makes the glycerol component of fats a glucogenic precursor, though it constitutes a small percentage of the total fat molecule.

Glucogenic Amino Acids

When protein is broken down, certain amino acids can be converted into intermediates of the citric acid cycle or pyruvate. These are known as glucogenic amino acids and are a vital source of glucose during prolonged fasting when glycogen stores are depleted. The alanine cycle, for instance, transports alanine from muscle tissue to the liver for conversion to pyruvate and then glucose.

Comparison of Glucose Production Pathways


Substrate for Glucose Production	Pathway Used	Convertible to Glucose?	Mechanism in Brief
Even-chain Fatty Acids	Beta-oxidation to Acetyl-CoA, which enters the Citric Acid Cycle.	No (in humans).	The conversion of pyruvate to acetyl-CoA is irreversible in humans. Acetyl-CoA cannot be converted back to pyruvate or any other intermediate that can produce a net gain of glucose.
Glycerol	Gluconeogenesis pathway after conversion to DHAP.	Yes.	Glycerol is a three-carbon molecule that can be converted into dihydroxyacetone phosphate (DHAP), a glycolytic intermediate that can proceed to glucose.
Lactate	Cori Cycle (Lactate to Pyruvate to Glucose).	Yes.	Produced by anaerobic metabolism, lactate is converted back to pyruvate in the liver, which is a substrate for gluconeogenesis.
Glucogenic Amino Acids	Gluconeogenesis pathway after conversion to pyruvate or TCA cycle intermediates.	Yes.	Protein breakdown yields specific amino acids whose carbon skeletons can be used to synthesize glucose.
Glycogen	Glycogenolysis.	Yes.	Glycogen is the body's stored form of glucose. It is broken down into glucose-6-phosphate and then glucose for release into the bloodstream.

Conclusion: The Final Answer Explained

The definitive answer to the question is that even-chain fatty acids cannot be used for the net production of glucose in humans. The metabolic block at the irreversible pyruvate dehydrogenase step prevents the conversion of acetyl-CoA, the end-product of fatty acid breakdown, into the necessary gluconeogenic precursor molecules. While the body is remarkably adept at generating glucose from other sources like lactate, glycerol, and certain amino acids, it cannot reverse the breakdown of typical fats for this purpose. This highlights a crucial and often misunderstood aspect of human energy metabolism, emphasizing why alternative fuel sources like ketones become important during prolonged fasting or low-carbohydrate conditions.

The Role of Acetyl-CoA and Ketone Bodies

It is important to note what happens to acetyl-CoA when gluconeogenesis is active and carbohydrate intake is low. Instead of entering the citric acid cycle (which is depleted of intermediates for gluconeogenesis), acetyl-CoA can be used to produce ketone bodies in the liver, a process called ketogenesis. The brain and other tissues can use these ketones as an alternative fuel source, effectively sparing the limited glucose supply for cells that depend on it, such as red blood cells. This metabolic flexibility is essential for survival during starvation or periods of intense energy demand.

For a deeper look into this fascinating metabolic process, consider exploring the detailed explanation on gluconeogenesis and fat metabolism available from the UCSF Diabetes Teaching Center, a reliable source on the topic.

Frequently Asked Questions

Yes, the glycerol component of triglycerides can be converted into glucose through gluconeogenesis, but the far more abundant fatty acid chains cannot.

The conversion of pyruvate to acetyl-CoA is catalyzed by the pyruvate dehydrogenase complex and is a metabolically irreversible reaction in humans, meaning there is no enzyme to reverse the process.

Glycogenolysis is the breakdown of stored glycogen into glucose, while gluconeogenesis is the synthesis of new glucose from non-carbohydrate precursors like amino acids and glycerol.

No, ketone bodies are an alternative fuel source produced from fatty acids in the liver during carbohydrate deprivation. They can be used for energy by the brain and other tissues, but they are not converted into glucose.

Plants and some bacteria possess a glyoxylate cycle, which contains enzymes (isocitrate lyase and malate synthase) that allow for the net synthesis of intermediates for gluconeogenesis from acetyl-CoA, a pathway lacking in humans.

During fasting, the body relies on gluconeogenesis, primarily using lactate, glycerol, and glucogenic amino acids to produce glucose, especially after liver glycogen stores are depleted.

Glucogenic amino acids are specific amino acids from protein that can be converted into glucose via the gluconeogenesis pathway. Examples include alanine and glutamine.