Introduction to Gluconeogenesis on the MCAT

November 28, 2023
15 min read


Reviewed by:

Rohan Jotwani

Former Chief Resident in Anesthesiology, Weill Cornell Medicine, & Admissions Officer, Columbia University

Reviewed: 11/28/23

Master gluconeogenesis on the MCAT with our comprehensive guide. Keep reading to learn more about carbohydrate metabolism and enhance your MCAT preparation.

Source: Medistudents

If you're preparing for the Medical College Admission Test (MCAT) and taking chemistry, you will be familiar with cellular processes. Among the essential cellular processes is gluconeogenesis, a fundamental metabolic pathway in which our bodies synthesize glucose, a primary energy source, from non-carbohydrate precursors like amino acids and glycerol.

Understanding this pathway in MCAT is crucial, as questions about it often appear in the Biological and Biochemical Foundations of Living Systems section. In this guide, you'll gain a comprehensive understanding of the critical reactions, enzymes, and regulatory mechanisms governing gluconeogenesis.

By the end of this blog, you'll be well-equipped to confidently tackle any MCAT gluconeogenesis questions, ensuring you're prepared to excel in this exam. So, let's master this essential topic for your MCAT success!

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How Does MCAT Cover Gluconeogenesis?

The MCAT assesses knowledge of gluconeogenesis through different question types, including conceptual understanding, integration with related pathways, problem-solving, experimental analysis, and critical thinking.

Why is only 1 NAD/NADH used/made in gluconeogenesis, but 2 NAD/NADH are  used/made in glycolysis? : r/Mcat

Source: Reddit

Conceptual Understanding

Here, candidates are presented with questions that assess their conceptual understanding of gluconeogenesis. These questions may inquire about the critical enzymes involved in the pathway, the substrates utilized, or the physiological significance of gluconeogenesis in maintaining energy homeostasis.

Integration With Related Pathways

Gluconeogenesis is connected with other metabolic pathways, particularly glycolysis. MCAT questions often require candidates to integrate their knowledge of gluconeogenesis with these related processes. 

This integration might mean figuring out how changes in enzyme activity affect glucose metabolism or how the pathway adjusts in different body conditions.


Candidates may encounter complex scenarios that demand applying their knowledge to solve problems. For instance, they might be tasked with calculating the energy cost of gluconeogenesis or predicting the consequences of a genetic mutation affecting a gluconeogenic enzyme.

Experimental Analysis

Some MCAT questions ask candidates to interpret data related to gluconeogenesis. This could involve analyzing graphs, charts, or empirical findings to conclude the regulation or efficiency of the pathway.

Critical Thinking

The MCAT may present scenarios in which candidates must think critically about the implications of perturbations in the pathway. They may be asked to predict the effects of hormonal fluctuations or enzyme deficiencies on gluconeogenesis and overall metabolic homeostasis.

To excel in the MCAT's evaluation of gluconeogenesis, aspiring medical students should thoroughly study the pathway, understand its regulation, practice problem-solving, know its integration with other concepts, and stay informed about the latest developments. 

By mastering these aspects, test-takers can confidently tackle gluconeogenesis-related questions and contribute to their overall success in the MCAT.

How Are Carbohydrates Digested?

Carbohydrates are one of the essential macronutrients our bodies require for energy. They are found in bread, rice, pasta, fruits, vegetables, and sweets. To make use of carbohydrates properly, our bodies need to break them down into smaller molecules that can be absorbed. This process primarily occurs in the digestive system. It involves several key steps:

  • Mouth: Digestion begins in the mouth with the mechanical action of chewing and the chemical action of salivary amylase. Salivary amylase, an enzyme produced by the salivary glands, starts breaking down complex carbohydrates (starches) into simpler sugars like maltose.
  • Stomach: Carbohydrates continue their journey into the stomach, where gastric juices and churning motions further mix and break down food. However, carbohydrate digestion mostly halts here, as the stomach's acidic environment inhibits salivary amylase's action.
  • Small Intestine: Most carbohydrate digestion occurs in the small intestine. Once partially digested food leaves the stomach and enters the duodenum (the first part of the small intestine), the pancreas releases pancreatic amylase, breaking down starches into maltose and other disaccharides.
  • Brush Border Enzymes: The small intestine's lining contains specialized brush border enzymes. These enzymes, including maltase, sucrase, and lactase, break down disaccharides into their constituent monosaccharides (glucose, fructose, and galactose). These monosaccharides can now be absorbed into the bloodstream.
  • Absorption: The final step involves the absorption of monosaccharides through the intestinal lining into the bloodstream. Glucose and galactose are absorbed via active transport, requiring energy, while fructose is absorbed via facilitated diffusion.
  • Transport to Cells: Once absorbed, glucose, fructose, and galactose are transported via the bloodstream to cells throughout the body. Cells use these sugars as an immediate energy source or store them as glycogen in the liver and muscles for later use.

It's important to note that not all carbohydrates are digested and absorbed similarly. Simple carbohydrates, like those found in table sugar or fruit, are rapidly broken down and can cause spikes in blood sugar levels. 

Complex carbohydrates, such as those in whole grains and legumes, take longer to digest due to their fibre content, resulting in more stable blood sugar levels.

Fermentation and Glycolysis

Fermentation and glycolysis are two fundamental biochemical processes that are pivotal in energy metabolism, particularly in the absence of oxygen or during periods of high energy demand. These processes, though related, have distinct characteristics and functions within living cells.


Glycolysis is a universal metabolic pathway found in nearly all living organisms, from bacteria to humans. It is the initial step in breaking down glucose or other hexose sugars to generate energy. Glycolysis occurs in the cytoplasm of cells and does not require oxygen, making it an anaerobic process.

The pathway consists of a series of enzymatic reactions that transform glucose into two molecules of pyruvate while simultaneously producing small amounts of adenosine triphosphate (ATP) and nicotinamide adenine dinucleotide (NADH), which are critical energy carriers in cells. Here's a simplified overview of glycolysis:

  1. Glucose Activation: In the first half of glycolysis, two ATP molecules are invested to activate glucose and split it into two glyceraldehyde-3-phosphate (G3P) molecules.
  2. Energy Generation: G3P is then converted into pyruvate through a series of enzymatic reactions, ultimately generating four molecules of ATP and two molecules of NADH.
  3. Pyruvate Formation: The end product of glycolysis is two pyruvate molecules, which can proceed to the next stages of cellular respiration if oxygen is available or enter fermentation pathways without oxygen.


Fermentation is a metabolic pathway that follows glycolysis when oxygen is scarce or unavailable. It is primarily responsible for regenerating NAD+ from the NADH produced during glycolysis. 

This regeneration of NAD+ is crucial because glycolysis requires NAD+ as a coenzyme to continue functioning. Without it, glycolysis would halt, disrupting the cell's energy production.

Fermentation can take various forms depending on the organism and the end products produced. Two common types of fermentation are lactic acid fermentation and alcoholic fermentation.

  1. Lactic Acid Fermentation: In lactic acid fermentation, pyruvate is converted into lactic acid. This process occurs in certain bacteria, muscle cells, and other organisms. The buildup of lactic acid can lead to muscle fatigue during strenuous exercise.
  2. Alcoholic Fermentation: Alcoholic fermentation, on the other hand, converts pyruvate into ethanol (alcohol) and carbon dioxide. This process is utilized by yeast and some bacteria in brewing and baking.

Key Differences

Here are the key differences between fermentation and glycolysis

  • Glycolysis is the initial metabolic pathway for glucose breakdown, producing ATP and NADH.
  • Fermentation follows glycolysis when oxygen is lacking and primarily regenerates NAD+.
  • Glycolysis is common to all living organisms and occurs in the cytoplasm.
  • Fermentation can take different forms depending on the organism and end products.
  • Both glycolysis and fermentation are anaerobic, meaning they do not require oxygen.

Glycolysis initiates the breakdown of glucose and produces energy-rich molecules like ATP and NADH. When oxygen is unavailable, fermentation pathways step in to regenerate NAD+ to sustain glycolysis, ensuring a continuous supply of energy for the cell. 

These processes are essential to cellular energy metabolism, allowing cells to adapt to changing conditions and energy demands.

The TCA Cycle

The Tricarboxylic Acid (TCA) Cycle, also known as the Krebs Cycle or Citric Acid Cycle, is a central metabolic pathway in eukaryotic cells' mitochondria. It is crucial in cellular respiration, where glucose and other carbon-based molecules are broken down to generate energy in the form of adenosine triphosphate (ATP). 

The TCA cycle is a series of chemical reactions that starts with the molecule acetyl-CoA and culminates in producing ATP and electron carriers, such as NADH and FADH2. Here's a simplified overview:

  1. Acetyl-CoA Entry: The cycle begins when acetyl-CoA, produced from the breakdown of glucose or fatty acids, enters the cycle by combining with a four-carbon compound called oxaloacetate. This forms a six-carbon compound, citrate.
  2. Series of Transformations: Citrate is then gradually transformed through a series of enzymatic reactions, releasing carbon dioxide and regenerating oxaloacetate. During these reactions, NADH and FADH2 are generated.
  3. Energy Production: The main purpose of the TCA cycle is to extract high-energy electrons stored in NADH and FADH2, which are then used in the electron transport chain (ETC) to generate ATP. For each turn of the cycle, three molecules of NADH, one molecule of FADH2, and one molecule of ATP are produced.
  4. Carbon Dioxide Release: Carbon dioxide is released as a waste product during the cycle.
  5. Cycle Continuation: Oxaloacetate, which is regenerated at the end of the cycle, can combine with another molecule of acetyl-CoA to continue the cycle, forming a continuous loop.

Key Functions and Significance

Let’s take a look at the key functions and significance of the TCA cycle:

  • Energy Production: The TCA cycle is a major source of cell ATP production. The high-energy electrons generated during the cycle are transferred to the electron transport chain, where they contribute to the synthesis of ATP through oxidative phosphorylation.
  • Carbon Skeleton Generation: Apart from energy production, the TCA cycle also serves as a source of carbon skeletons that can be used to synthesize various biomolecules like amino acids, nucleotides, and fatty acids.
  • Redox Reactions: The TCA cycle is a source of reducing equivalents in NADH and FADH2, which carry high-energy electrons. These molecules are crucial in maintaining the cellular redox balance and essential for other metabolic processes.
  • Central Hub: The TCA cycle is often called the central hub of metabolism because it connects with other metabolic pathways, including glycolysis, fatty acid oxidation, and amino acid metabolism.

The TCA cycle is a fundamental metabolic pathway central to energy production and the generation of essential biomolecules. It's a highly regulated and interconnected pathway vital for the overall functioning of cells and, by extension, the entire organism. Understanding the TCA cycle is crucial for grasping the complexities of cellular respiration and metabolism.

Example of Carbohydrate Metabolism MCAT Questions

Here are some examples of MCAT gluconeogenesis questions:

Passage-Based Questions

Passage-based questions require reading and understanding scientific passages before answering a series of questions. These questions assess your factual knowledge and ability to apply critical thinking and problem-solving skills to unfamiliar scenarios. The passages are typically based on real-world scientific research, experiments, or studies.

Question #1

In a recent study, researchers investigated the regulation of glycolysis in response to glucose availability in muscle cells. They exposed the cells to varying glucose concentrations and monitored the activity of key glycolytic enzymes. 

Results showed that high glucose concentrations led to increased activity of phosphofructokinase (PFK), a rate-limiting enzyme in glycolysis. What can you infer about the regulation of glycolysis in muscle cells in response to glucose availability?

A. High glucose concentrations inhibit glycolysis.

B. PFK activity is independent of glucose concentration.

C. Glycolysis is upregulated when glucose levels are high.

D. PFK is not involved in the glycolytic pathway.

Answer: C. Glycolysis is upregulated when glucose levels are high.

Question #2

A group of scientists experimented to study the effects of insulin on glucose transporters in adipose tissue. They exposed adipocytes to insulin and measured the levels of GLUT4, a glucose transporter protein. Results showed a significant increase in GLUT4 translocation to the cell membrane in the presence of insulin. What is the primary role of insulin in glucose transport in adipose tissue?

A. Insulin inhibits GLUT4 translocation.

B. Insulin decreases glucose uptake in adipocytes.

C. Insulin stimulates GLUT4 translocation to the cell membrane.

D. GLUT4 is not involved in glucose transport in adipose tissue.

Answer: C. Insulin stimulates GLUT4 translocation to the cell membrane.

Question #3

A study investigated the effects of a genetic mutation in the enzyme pyruvate kinase (PK) on glycolysis. Individuals with this mutation showed decreased PK activity. The researchers observed that these individuals had reduced levels of ATP and increased levels of fructose-1,6-bisphosphate in their muscle cells." What can you conclude about the impact of the PK mutation on glycolysis?

A. The mutation increases PK activity.

B. Glycolysis is unaffected by the PK mutation.

C. The mutation impairs glycolysis and ATP production.

D. Fructose-1,6-bisphosphate levels are decreased in mutant cells.

Answer: C. The mutation impairs glycolysis and ATP production.

Question #4

A clinical trial examined the effects of a drug that inhibits gluconeogenesis in patients with type 2 diabetes. The drug was administered for six weeks and monitored blood glucose levels. Results showed a significant decrease in fasting blood glucose levels in patients treated with the drug compared to the control group. What is the likely mechanism of action of the drug that led to reduced blood glucose levels?

A. The drug enhances gluconeogenesis.

B. The drug impairs insulin sensitivity.

C. The drug inhibits gluconeogenesis.

D. The drug increases blood glucose levels.

Answer: C. The drug inhibits gluconeogenesis.

Question #5

An experiment investigated the effects of AMP-activated protein kinase (AMPK) activation on glucose metabolism. Researchers exposed liver cells to an AMPK activator and measured the levels of glucose-6-phosphatase (G6Pase), an enzyme involved in gluconeogenesis. 

Results showed a significant decrease in G6Pase activity. What is the likely consequence of AMPK activation on glucose metabolism in liver cells?

A. AMPK activation increases G6Pase activity.

B. AMPK activation has no impact on G6Pase activity.

C. AMPK activation decreases G6Pase activity.

D. G6Pase is not involved in gluconeogenesis.

Answer: C. AMPK activation decreases G6Pase activity.

These examples show the diverse range of passage-based questions you may encounter on the MCAT. Success on the MCAT requires a solid foundation in scientific concepts and strong reading comprehension, critical thinking, and reasoning skills. Practicing with sample passages and questions is essential to prepare effectively for this challenging examination.

Standalone Questions

Standalone questions test your knowledge and problem-solving skills without a passage or context. These questions require you to apply your understanding of carbohydrate metabolism principles to solve specific problems or answer discrete questions. Here are some examples:

Question #1

Which enzyme catalyzes the conversion of glucose-6-phosphate to glucose in the final step of gluconeogenesis?

A. Glucose-6-phosphatase B. Hexokinase C. Glucokinase D. Phosphofructokinase-1

Answer: A. Glucose-6-phosphatase

Question #2

In glycolysis, which molecule is both a reactant and a product of the reaction catalyzed by phosphofructokinase-1 (PFK-1)?

A. Fructose-1,6-bisphosphate 

B. Glucose-6-phosphate 


D. Phosphoenolpyruvate

Answer: A. Fructose-1,6-bisphosphate

Question #3

During prolonged fasting, what is the primary source of glucose production to maintain blood glucose levels?

A. Glycogenolysis 

B. Glycolysis 

C. Gluconeogenesis 

D. Lipolysis

Answer: C. Gluconeogenesis

Question #4

Which of the following hormones stimulates glycogen synthesis and inhibits glycogen breakdown in the liver?

A. Insulin 

B. Glucagon 

C. Epinephrine 

D. Cortisol

Answer: A. Insulin

Question #5

Which metabolic pathway is most likely impaired in a patient with a deficiency in the enzyme pyruvate kinase (PK)?

A. Glycolysis 

B. Gluconeogenesis 

C. Glycogenolysis 

D. Pentose phosphate pathway

Answer: A. Glycolysis

These standalone questions assess your knowledge of carbohydrate metabolism concepts and your ability to apply them to specific scenarios. Practicing with such questions can help you reinforce your understanding and effectively prepare for carbohydrate metabolism questions on the MCAT.

Female student concentrating while studying

FAQs: Introduction to Gluconeogenesis

Keep reading for some questions related to gluconeogenesis on the MCAT. 

1. What Happens During Gluconeogenesis?

Gluconeogenesis involves the synthesis of glucose from non-carbohydrate precursors, such as amino acids, lactate, and glycerol. This pathway allows the body to maintain blood glucose levels when dietary sources of glucose are scarce, during fasting, or in cases of high energy demand.

2. Do I Have To Memorize Glycolysis for the MCAT?

Yes, you may need to memorize some concepts. While you don't necessarily need to memorize every enzyme or intermediate, you should have a grasp of the key steps, substrates, products, and energy changes involved in glycolysis. MCAT gluconeogenesis questions may require you to apply your knowledge of it to various scenarios.

3. What Is the Difference Between Glycolysis and Gluconeogenesis?

The main difference between glycolysis and gluconeogenesis is their direction and purpose:

  • Glycolysis: A catabolic pathway that breaks down glucose (or other carbohydrates) into two molecules of pyruvate, producing ATP and NADH. It occurs in the cytoplasm and is primarily involved in energy production.
  • Gluconeogenesis: An anabolic pathway synthesizing glucose from non-carbohydrate precursors, like amino acids and lactate. It occurs mainly in the liver and kidneys and maintains blood glucose levels during fasting or high energy demand.

Glycolysis and gluconeogenesis are regulated in a way that ensures they don't happen simultaneously in the same cell to avoid wasteful "futile cycles." 

4. Is Gluconeogenesis Catabolic or Anabolic?

Gluconeogenesis is an anabolic pathway. Anabolic pathways involve the synthesis of complex molecules from simpler ones and typically require an input of energy. In the case of gluconeogenesis, glucose is synthesized from non-carbohydrate precursors, which consume energy in the form of ATP and GTP.

5. What Is the Main Purpose of Gluconeogenesis?

The primary purpose of gluconeogenesis is to maintain blood glucose levels within a narrow range, particularly when dietary sources of glucose are limited. It ensures a steady supply of glucose to meet the energy needs of the brain and other glucose-dependent tissues, even during fasting or when carbohydrates are scarce in the diet.

6. Does Gluconeogenesis Produce ATP?

Gluconeogenesis consumes ATP and GTP as energy sources to convert non-carbohydrate precursors into glucose. It is an energetically costly process. However, once glucose is synthesized, it can produce ATP in glycolysis, but this occurs separately from the gluconeogenic pathway.

Final Thoughts

Understanding gluconeogenesis is vital for anyone preparing for the MCAT, as it represents a critical aspect of carbohydrate metabolism. While memorization may be required for some key concepts, grasping the broader principles and the differences between gluconeogenesis and glycolysis is equally important.

Gluconeogenesis on the MCAT may seem complex, but a thorough understanding of gluconeogenesis is achievable through diligent study and practice, making it a valuable component of MCAT preparation for aspiring medical professionals.

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