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Carbohydrate Metabolism

Author: Sophia

what's covered
In this lesson, you will learn about how sugars are metabolized by the body. Specifically, this lesson will cover:

Table of Contents

1. Carbohydrates

Carbohydrates are organic molecules composed of carbon, hydrogen, and oxygen atoms. The family of carbohydrates includes both simple and complex sugars.

EXAMPLE

Glucose and fructose are examples of simple sugars, and starch, glycogen, and cellulose are all examples of complex sugars.

The complex sugars are also called polysaccharides and are made of multiple monosaccharide molecules. Polysaccharides serve as energy storage (e.g., starch and glycogen) and as structural components (e.g., chitin in insect exoskeletons and cellulose in plant cell walls).

During digestion, carbohydrates are broken down into simple, soluble sugars that can be transported across the intestinal wall into the circulatory system to be transported throughout the body. Carbohydrate digestion begins in the mouth with the action of salivary amylase on starches and ends with monosaccharides being absorbed across the epithelium of the small intestine. Once the absorbed monosaccharides are transported to the tissues, the process of cellular respiration begins, during which ATP is produced from breaking down glucose. This lesson will focus first on glycolysis, a process where the monosaccharide glucose is oxidized, releasing the energy stored in its bonds to produce ATP.

Cellular Respiration—Cellular respiration oxidizes glucose molecules through glycolysis, the citric acid cycle, and oxidative phosphorylation to produce ATP.

term to know
Cellular Respiration
Production of ATP from glucose oxidation via glycolysis, the citric acid cycle, and oxidative phosphorylation.


2. Glycolysis

Glucose is the body’s most readily available source of energy. After digestive processes break polysaccharides down into monosaccharides, including glucose, the monosaccharides are transported across the wall of the small intestine and into the circulatory system, which transports them to the liver. In the liver, hepatocytes either pass the glucose on through the circulatory system or store excess glucose as glycogen. Cells in the body take up the circulating glucose in response to insulin and, through a series of reactions called glycolysis, transfer some of the energy in glucose to ADP to form ATP. The last step in glycolysis produces the product pyruvate.

Now, the process of glycolysis begins. Glycolysis consists of 10 steps, but has three major phases that are most important to remember so that you grasp what is happening:

  1. Activation—A six-carbon glucose molecule gets another phosphate added to it. The phosphate comes from ATP. This commits the molecule to glycolysis and provides energy for the process. It is much like the battery of a car providing energy to start the engine.
  2. Cleavage—Here, the six-carbon molecule with two phosphates gets split into two three-carbon molecules, each with one phosphate.
  3. Rearrangement and energy production—In this phase, the energy payoff happens. Each of these three-carbon phosphate molecules gets rearranged. Two more phosphates get added and, ultimately, the phosphates get removed and passed to ADP to make four ATP molecules. Also in this process, electrons get passed to two NAD⁺ to make two NADH. What remains are two three-carbon pyruvate molecules, which can proceed further into carbohydrate metabolism.
learn more
To read more about the steps of glycolysis, please visit the supplemental document Biochemical Details of Carbohydrate Metabolism.pdf.

As shown in the image below, the net effect of glycolysis is that two ATP (four ATP from step 3 [rearrangement] and two ATP from step 1 [glycolysis] = two ATP), three NADH, and two pyruvate molecules are produced.

Summary of the Events in the Three Phases of Glycolysis—Activation, Cleavage, and Rearrangement and Energy Production. Black circles are carbon atoms, blue circles with P represent phosphate groups, and the blue circle with Pᵢ represents free inorganic phosphate.

In summary, one glucose molecule breaks down into two pyruvate molecules and creates two net ATP molecules and two NADH molecules by glycolysis. Therefore, glycolysis generates energy for the cell and creates pyruvate molecules that can be processed further through the aerobic citric acid cycle (also called the Krebs cycle or tricarboxylic acid cycle/TCA cycle); converted into lactic acid or alcohol (in yeast) by fermentation (which is anaerobic); or used later to produce glucose through gluconeogenesis.

terms to know
Glycolysis
The series of metabolic reactions that breaks down glucose into pyruvate and produces ATP.
Pyruvate
The three-carbon end product of glycolysis and starting material that is converted into acetyl-CoA that enters the citric acid cycle.
Citric Acid Cycle
Also called the Krebs cycle or the tricarboxylic acid cycle (TCA); converts pyruvate into CO₂ and high-energy FADH₂, NADH, and ATP molecules.

2a. Aerobic vs. Anaerobic Respiration

In the presence of oxygen, a carbon is removed from pyruvate, and a coenzyme is added to make acetyl coenzyme A (acetyl-CoA), which enters the citric acid cycle. The carbon that is removed is released as carbon dioxide. In the citric acid cycle, additional energy is extracted from acetyl-CoA as electrons are transferred to the receptors NAD⁺, GDP, and FAD, and more carbon dioxide is produced as a “waste product.” The NADH and FADH₂ pass electrons on to the electron transport chain, which uses the transferred energy to produce ATP; this process is where most of the energy from glucose catabolism is extracted. As the terminal step in the electron transport chain, oxygen is the terminal electron acceptor and creates water inside the mitochondria. By this time, all of the carbons from the original glucose have been released as carbon dioxide, energy has been stored in ATP, and oxygen has been consumed.

When oxygen is limited or absent, pyruvate enters an anaerobic pathway called fermentation. In these reactions, pyruvate can be converted into lactic acid. In addition to generating an additional ATP, this pathway serves to keep the pyruvate concentration low so glycolysis continues, and it oxidizes NADH into the NAD⁺ needed by glycolysis. In this reaction, lactic acid replaces oxygen as the final electron acceptor. Anaerobic respiration occurs in most cells of the body when oxygen is limited or mitochondria are absent or nonfunctional. For example, because erythrocytes (red blood cells) lack mitochondria, they must produce their ATP from glycolysis alone.

This is an effective pathway of ATP production for short periods of time, ranging from seconds to a few minutes. The lactic acid produced diffuses into the plasma and is carried to the liver, where it is converted back into pyruvate or glucose via the Cori cycle (also known as the lactic acid cycle). Similarly, when a person exercises, muscles use ATP faster than oxygen can be delivered to them. They depend on glycolysis and lactic acid production for rapid ATP production.

reflect
Have your muscles ever felt particularly stiff, fatigued, or painful following a particularly vigorous exercise session?

This occurs because of fermentation. When lactic acid accumulates in your muscle cells as a result of fermentation during strenuous exercise, this lactic acid buildup causes muscle stiffness and fatigue.

Summary of Aerobic vs. Anaerobic Respiration—The process of anaerobic respiration converts glucose into two lactate molecules in the absence of oxygen (dotted red box) or within erythrocytes that lack mitochondria. During aerobic respiration, glucose is oxidized into two pyruvate molecules. The pyruvate molecules then get converted to acetyl-CoA, which enters the citric acid cycle; there, they get broken down to make ATP, carbon dioxide, and electrons (transferred to NADH). The NADH molecules transfer electrons to the electron transport chain and ultimately to oxygen, which gets consumed to make water. The movement of electrons through the chain transfers energy to make ATP.

terms to know
Terminal Electron Acceptor
Oxygen, the recipient of the free hydrogen at the end of the electron transport chain.
Fermentation
A process that occurs in the absence of oxygen in which pyruvate is converted into alcohol or lactic acid and some ATP is produced but without going through the citric acid cycle and the electron transport chain.


3. Citric Acid Cycle

The pyruvate molecules generated during glycolysis are transported across the mitochondrial membrane into the inner mitochondrial matrix, where they are metabolized by enzymes in a pathway called the citric acid cycle. As noted above, the citric acid cycle is also commonly called the Krebs cycle or the tricarboxylic acid (TCA) cycle. During the citric acid cycle, high-energy molecules, including ATP, NADH, and FADH₂, are created. NADH and FADH₂ then pass electrons through the electron transport chain in the mitochondria to generate more ATP molecules.

Citric Acid Cycle—During the citric acid cycle, each pyruvate that is generated by glycolysis is converted into a two-carbon acetyl-CoA molecule. The acetyl-CoA is systematically processed through the cycle and produces high-energy NADH, FADH2, and ATP molecules.

The three-carbon pyruvate molecule generated during glycolysis moves from the cytoplasm into the mitochondrial matrix, where it is converted by the enzyme pyruvate dehydrogenase into a two-carbon acetyl coenzyme A (acetyl-CoA) molecule.

term to know
Acetyl Coenzyme A (Acetyl-CoA)
The starting molecule of the citric acid cycle.


4. Oxidative Phosphorylation and the Electron Transport Chain

The electron transport chain (ETC) uses the NADH and FADH₂ produced by glycolysis and the citric acid cycle to generate ATP. Electrons from NADH and FADH₂ are transferred through protein complexes embedded in the inner mitochondrial membrane by a series of enzymatic reactions.

The ETC consists of a series of four enzyme complexes (Complex I–Complex IV) and two coenzymes (ubiquinone and cytochrome c), which act as electron carriers and proton pumps used to transfer H⁺ from inside the inner membrane into the space between the inner and outer mitochondrial membranes. The ETC couples the transfer of electrons between a donor (like NADH) and an electron acceptor (like O₂) with the transfer of protons (H⁺ ions) across the inner mitochondrial membrane, enabling oxidative phosphorylation, which is the process that converts high-energy NADH and FADH₂ into ATP.

In the presence of oxygen, energy is passed, stepwise, through the electron carriers to gradually collect the energy needed to attach a phosphate to ADP and produce ATP. The role of molecular oxygen, O₂, is as the terminal electron acceptor for the ETC. This means that once the electrons have passed through the entire ETC, they must be passed to another, separate molecule. These electrons, O₂, and H⁺ ions from the matrix combine to form new water molecules.

key concept
This is the basis for your need to breathe in oxygen. Without oxygen, electron flow through the ETC ceases.

Electron Transport Chain—The electron transport chain is a series of electron carriers and ion pumps that are used to pump H⁺ ions out of the inner mitochondrial matrix.

The electrons released from NADH and FADH₂ are passed along the chain by each of the carriers. Each of these reactions releases a small amount of energy, which is used to pump H⁺ ions across the inner membrane. Ultimately, the electrons are passed from the final carrier, cytochrome c, to molecular oxygen, which gets split and combined with protons in the matrix to make water. The accumulation of these protons in the space between the membranes creates a proton gradient with respect to the mitochondrial matrix in which the energy is stored.

Also embedded in the inner mitochondrial membrane is a protein pore complex called ATP synthase. ATP is made by this enzyme through the process of chemiosmosis, which couples the synthesis of ATP to the proton gradient across the membrane. Effectively, the ATP synthase is a turbine that is powered by the flow of H⁺ ions across the inner membrane down a gradient and into the mitochondrial matrix. As the H⁺ ions traverse the complex, the shaft of the complex rotates. This rotation enables other portions of ATP synthase to use the energy from the proton gradient to create ATP from ADP and Pᵢ. In accounting for the total number of ATP produced per glucose molecule through aerobic respiration, it is important to remember the following points:

  • A net of two ATP is produced through glycolysis (four produced and two consumed during the energy-consuming stage). However, these two ATP are used for transporting the NADH produced during glycolysis from the cytoplasm into the mitochondria (except in red blood cells, which have no mitochondria). Therefore, the net production of ATP during glycolysis is zero.
  • In all phases after glycolysis, the number of ATP, NADH, and FADH₂ produced must be multiplied by two to reflect how each glucose molecule produces two pyruvate molecules.
  • In the ETC, about three ATP are produced for every oxidized NADH. However, only about two ATP are produced for every oxidized FADH₂. The electrons from FADH₂ produce less ATP because they start at a lower point in the ETC (Complex II) compared with the electrons from NADH (Complex I) (see the image above).
Therefore, for every glucose molecule that enters aerobic respiration, a net total of 36 ATPs is produced (see the image below).

Energy Produced by Carbohydrate Metabolism—Carbohydrate metabolism involves glycolysis, the citric acid cycle, and the electron transport chain.

think about it
You might notice that the number of ATP produced per molecule of glucose is cited in different sources as anywhere from between 28 and 38. How can this be, and what is the right answer?

A more detailed accounting of the complexities of cellular respiration has revealed that when losses from leaky membranes and costs for transporting ADP and pyruvate are included, the actual number is closer to 30 and may vary across species. The good news is that a precise number is not all that important. The key takeaway is that aerobic respiration produces far more ATP (~30 ATP/glucose) compared with anaerobic respiration (2 ATP/glucose).

terms to know
Electron Transport Chain (ETC)
The ATP production pathway in which electrons are passed through a series of oxidation-reduction reactions that forms water and produces a proton gradient.
Oxidative Phosphorylation
The process that converts high-energy NADH and FADH₂ into ATP.
ATP Synthase
The protein pore complex that creates ATP.


5. Gluconeogenesis

Gluconeogenesis is the synthesis of new glucose molecules from pyruvate, lactate, glycerol, or the amino acids alanine or glutamine. This process takes place primarily in the liver during periods of low glucose—that is, under conditions of fasting, starvation, and low carbohydrate diets. So, why would the body create something it has just spent a fair amount of effort to break down?

Certain key organs, including the brain, can use only glucose as an energy source. Therefore, it is essential that the body maintain a minimum blood glucose concentration. When the blood glucose concentration falls below that certain point, new glucose is synthesized by the liver to raise the blood concentration to normal.

Gluconeogenesis is not simply the reverse of glycolysis. There are some important differences. Pyruvate is a common starting material for gluconeogenesis. First, the pyruvate is converted into oxaloacetate. Oxaloacetate then serves as a substrate for the enzyme phosphoenolpyruvate carboxykinase (PEPCK), which transforms oxaloacetate into PEP. From this step, gluconeogenesis is nearly the reverse of glycolysis.

learn more
To read more about the steps of gluconeogenesis, please visit the supplemental document Biochemical Details of Carbohydrate Metabolism.pdf.

As will be discussed in a future lesson that addresses lipolysis, fats can be broken down into glycerol, which can be phosphorylated to form dihydroxyacetone phosphate, or DHAP. DHAP can either enter the glycolytic pathway or be used by the liver as a substrate for gluconeogenesis.

Gluconeogenesis—Gluconeogenesis is the synthesis of glucose from pyruvate, lactate, glycerol, alanine, or glutamate.

IN CONTEXT

Aging and the…
Body’s Metabolic Rate

The human body’s metabolic rate decreases nearly 2% per decade after age 30. Changes in body composition, including reduced lean muscle mass, are mostly responsible for this decrease. The most dramatic loss of muscle mass, and consequential decline in metabolic rate, occurs between 50 and 70 years of age. Loss of muscle mass is the equivalent of reduced strength, which tends to inhibit seniors from engaging in sufficient physical activity. This results in a positive-feedback system where the reduced physical activity leads to even more muscle loss, further reducing metabolism.

There are several things that can be done to help prevent general declines in metabolism and to fight back against the cyclic nature of these declines. These include eating breakfast, eating small meals frequently, consuming plenty of lean protein, drinking water to remain hydrated, exercising (including strength training), and getting enough sleep. These measures can help keep energy levels from dropping and curb the urge for increased calorie consumption from excessive snacking.

Although these strategies are not guaranteed to maintain metabolism, they do help prevent muscle loss and may increase energy levels. Some experts also suggest avoiding sugar, which can lead to excess fat storage. Spicy foods and green tea might also be beneficial. Because stress activates cortisol release, and cortisol slows metabolism, avoiding stress, or at least practicing relaxation techniques, can also help.

summary
In this lesson, you learned about how the body metabolizes carbohydrates. First, you reviewed the importance of carbohydrates, specifically carbohydrate metabolism and how complex sugars are broken down into simple sugars. Then, you explored how the body breaks down glucose into pyruvate and produces ATP by glycolysis and how this process differs under aerobic vs. anaerobic respiration. You then examined how the citric acid cycle converts pyruvate into CO₂ and high-energy molecules. Finally, you learned about how oxidative phosphorylation and the electron transport chain enable conversion of high-energy NADH and FADH₂ into ATP and about how gluconeogenesis synthesizes glucose from pyruvate or other molecules.

SOURCE: THIS TUTORIAL HAS BEEN ADAPTED FROM OPENSTAX “ANATOMY AND PHYSIOLOGY 2E”. ACCESS FOR FREE AT OPENSTAX.ORG/BOOKS/ANATOMY-AND-PHYSIOLOGY-2E/PAGES/1-INTRODUCTION. LICENSE: CREATIVE COMMONS ATTRIBUTION 4.0 INTERNATIONAL.

Terms to Know
ATP Synthase

The protein pore complex that creates ATP.

Acetyl Coenzyme A (Acetyl-CoA)

The starting molecule of the citric acid cycle.

Cellular Respiration

Production of ATP from glucose oxidation via glycolysis, the citric acid cycle, and oxidative phosphorylation.

Citric Acid Cycle

Also called the Krebs cycle or the tricarboxylic acid cycle (TCA); converts pyruvate into CO₂ and high-energy FADH₂, NADH, and ATP molecules.

Electron Transport Chain (ETC)

The ATP production pathway in which electrons are passed through a series of oxidation-reduction reactions that forms water and produces a proton gradient.

Fermentation

A process that occurs in the absence of oxygen in which pyruvate is converted into alcohol or lactic acid and some ATP is produced but without going through the citric acid cycle and the electron transport chain.

Glycolysis

The series of metabolic reactions that breaks down glucose into pyruvate and produces ATP.

Oxidative Phosphorylation

The process that converts high-energy NADH and FADH₂ into ATP.

Pyruvate

The three-carbon end product of glycolysis and starting material that is converted into acetyl-CoA that enters the citric acid cycle.

Terminal Electron Acceptor

Oxygen, the recipient of the free hydrogen at the end of the electron transport chain.