Welcome to our in-depth article on Introduction to Metabolism and Oxidative Phosphorylation. This guide is specifically designed for healthcare professionals, including doctors, nurses, paramedics, and pharmacists, as well as biochemistry students, and nursing and nutrition students preparing for medical licensing exams such as MBBS, nursing, and paramedics. We cover everything you need to know about metabolism and oxidative phosphorylation, from the role of enzymes and the electron transport chain to the production of ATP (adenosine triphosphate), the primary energy currency of cells, and the impact of metabolic disorders on the body. Our article is written by experts in the field, ensuring that you're getting the most accurate and reliable information. Our goal is to help you understand how your body produces and uses energy, and how to maintain a healthy metabolism. If you're looking for a comprehensive guide to metabolism and oxidative phosphorylation, this is the right article for you.
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| Oxidative Phosphorylation and Production of ATP From Biochemistry Library of H.E.S (Health, Education, and Skills) |
What is Metabolism?
All the chemical processes (reactions) that occur within the tissues of the living organism in order to maintain life is called Tissue Metabolism or simply Metabolism.
As long as the food is in the gastrointestinal tract (GIT) it is digestion, not metabolism.
Metabolic processes include
- Breakdown of nutrients (catabolism) to release energy,
- Synthesis of molecules (anabolism) needed for growth, and
- Repair, and the elimination of waste products.
The rate of metabolism, also known as metabolic rate, can vary among individuals and is influenced by factors such as age, sex, body composition, and hormone levels. A high metabolic rate means that the body is burning more energy, while a low metabolic rate means that the body is burning less energy.
There are three main types of metabolism: Catabolism, Anabolism, and Amphibolism.
a. Catabolism:
It is the process of breaking down molecules to release energy, such as the breakdown of glucose to release ATP (adenosine triphosphate) which is the primary energy currency of cells.
- All catabolic reactions are Exergonic Reactions i.e. they produce energy.
- Glycolysis (Breakdown of Glucose), and Beta-Oxidation of Fatty acids are some examples of catabolism.
It is the process of using energy to build molecules, such as the synthesis of proteins and nucleic acids.
- All anabolic reactions are Endergonic Reactions i.e. they utilize energy.
c. Amphibolism:
It is a type of metabolism that involves both catabolic and anabolic processes.
- One example of this is the citric acid cycle, also known as the Krebs cycle or the Tricarboxylic acid (TCA) cycle.
- The citric acid cycle is a series of chemical reactions that occur in the mitochondria of cells, where it converts acetyl-CoA, obtained from the breakdown of carbohydrates, fats, and proteins, into carbon dioxide and water. It also generates energy in the form of ATP and produces intermediate compounds that can be used in other metabolic pathways. The citric acid cycle is considered amphibolic because it both breaks down and synthesizes molecules.
The term Energy as used in Metabolism
- Energy is the ability to do work, which can take different forms such as chemical energy stored in molecules or heat energy.
- This can take different forms, such as chemical energy stored in molecules, or heat energy in the form of thermal energy.
- The changes in enthalpy, entropy and free energy can be used to predict the direction of a metabolic reaction and the amount of energy that will be released or consumed by it.
I. Low Energy Phosphate Compounds in Biological Systems
- They are phosphate-containing compounds and have free energy of less than 4000 cal/mole.
- Examples include Glucose-6-Phosphate, Glycerol-3-Phosphate, and AMP (Adenine Mononucleotide Phosphate).
II. High Energy Phosphate Compounds in Biological Systems
- High-energy phosphate compounds refer to molecules that contain a high amount of potential energy stored in the form of a Phosphoanhydride bond.
A Phosphoanhydride bond is a type of chemical bond that is formed between two phosphorus atoms and two oxygen atoms. It is characterized by the presence of two phosphoryl (-PO3) groups and two Anhydride (-O-) groups.
- These molecules can transfer this energy to other molecules through the hydrolysis of the bond, releasing the stored energy in the process.
- The energy stored in the high-energy phosphate bond between the second and third phosphate groups of ATP is used to fuel metabolic reactions in cells.
- The most common high-energy phosphate compounds are Adenosine Triphosphate (ATP) and Guanosine Triphosphate (GTP), while others are Cytosine Triphosphate (CTP), and Uridine Triphosphate (UTP).
- Adenosine Triphosphate (ATP) is the primary energy currency of cells, it provides energy for a wide variety of cellular processes such as muscle contraction, protein synthesis, and active transport.
- Guanosine Triphosphate (GTP) is similar to ATP, but it is also involved in intracellular signaling pathways, it can act as a cofactor to enzymes that are involved in the regulation of gene expression, cell division, and cell signaling.
- Uridine Triphosphate (UTP) is involved in the process of protein synthesis, where it is used as a substrate in the formation of peptide bonds between amino acids. UTP forms a bond with the carboxyl group of an amino acid, creating a new molecule called an aminoacyl-tRNA. This molecule then delivers the amino acid to the ribosome, where it is incorporated into a growing polypeptide chain.
- Cytosine Triphosphate (CTP) is involved in the process of lipid metabolism, it is used as a substrate in the formation of Phosphatidylcholine, Phosphatidylethanolamine, and Sphingomyelin. These are all important phospholipids that are found in cell membranes and play important roles in maintaining membrane structure and function.
- These high-energy phosphate compounds are synthesized in a process called cellular respiration, in which glucose is broken down to release energy in the form of ATP and GTP. These molecules are then used to drive other cellular processes that require energy.
- High-energy phosphate compounds can produce energy greater than 8000 cal/mole
III. Very High Energy Phosphate Compounds in Biological Systems
- They are also Phosphate-containing compounds and have energy higher than ATP.
- They have free energy of hydrolysis greater than 10,000 cal/mole.
- Examples of very high-energy phosphate compounds are 1,3-bisphosphoglycerate, Phosphocreatine (or Creatine Phosphate), and Phosphoenolpyruvate.
Some Thermodynamic terms as used in Metabolism
a. Enthalpy is a measure of the total energy of a system, including both the internal energy and the energy associated with its position in a gravitational field.
- It is the measure of the changes in the heat of the reactants and products.
- Enthalpy changes can occur during chemical reactions, such as the breaking or forming of chemical bonds.
b. Entropy is a measure of the disorder or randomness of reactants and products.
- Generally, reactions that release energy tend to increase the entropy of a system.
c. Free energy is the energy that is available to do work in a system.
- It is the sum of the enthalpy and the product of the entropy and the absolute temperature of the system.
- It can be used to predict the direction in which a reaction proceeds spontaneously.
- Reactions that have a negative free energy change are thermodynamically favorable and tend to occur spontaneously.
For example, in the citric acid cycle, the conversion of acetyl-CoA to carbon dioxide and water releases energy in the form of heat and in the form of ATP. This reaction is exothermic and the entropy of the system increases because the number of possible energy states increases as CO2 and H2O are produced.
Chemical events taking place in energy production by ATP
- ATP consists of a molecule of Adenosine to which three phosphate groups are attached.
- Hydrolysis of ATP releases Phosphate, thus releasing energy.
- In the case of ATP, the energy-rich bond that is broken is the bond between the second and third phosphate groups (P-O-P).
- The chemical equation for the hydrolysis of ATP is:
- The energy released in this reaction is used to drive various cellular processes such as muscle contraction, active transport, and biosynthesis.
- ADP (High Energy Phosphate Compound) is produced when Phosphate is removed from ATP.
- AMP (Low Energy Phosphate Compound) is produced when two phosphates either one at a time or two together are removed from ATP.
- When two Phosphates are removed together, they are called Pyrophosphate.
- The standard free energy produced by the release of one phosphate at a time is approximately -7300 cal/mole for each of the two terminal Phosphate Groups.
- Interestingly if Pyrophosphate i.e. 2-Phosphates together are removed at the same time, the energy released will not double i.e. it will not be -14,600 cal/mole, it will only be -8600 cal/mole.
Oxidative Phosphorylation | Electron Transport Chain
- It is also called "Electron Transport Chain (ETC)" or "Respiratory Chain"
In simple words, Oxidative phosphorylation is a process that converts the energy from the food we eat into a form that our cells can use, called ATP, by creating a flow of electrons and protons.
- This process takes place in the cells of plants and animals, including humans, to generate energy.
- Think of it like a power station inside your cells.
- Just like a power station that burns fuel to create electricity, the cells in our body burn food to create energy.
- The food we eat is broken down into small molecules called glucose and fatty acids.
- These molecules are then transported into the cell's power station, called the mitochondria, where they are "burned" to release energy.
- During this burning process, electrons are removed from the glucose and fatty acids and passed along a chain of proteins in the mitochondria, creating a flow of electrons.
- This flow of electrons generates a small electrical current, just like how a hydroelectric power station generates electricity from the flow of water.
- The electrical current is used to pump protons (H+) across a membrane inside the mitochondria, creating a gradient of protons.
- This gradient is like a reservoir of energy that can be used to generate ATP, the main energy currency of the cell.
- Finally, the protons flow back across the membrane through a special protein called ATP synthase, which uses the energy of the flowing protons to generate ATP.
An overall biochemical mechanism of Oxidative Phosphorylation
- Oxidative Phosphorylation is a series of electron carriers, containing FAD, NAD, FMN, Coenzyme Q, and Cytochromes (b, c1, c, a+a3), collectively known as Electron Transport Chain (ETC).
- Electron Transport Chain passes on electrons from NADH2 or FADH2 to molecular Oxygen, forming a molecule of water and generating energy, which is captured in the form of ATP through the following steps
- The metabolic intermediate of glucose (Pyruvate and Acetyl-CoA) and fatty acids (Acetyl-CoA and Beta-Hydroxybutyrate) donates electrons to coenzymes i.e NAD and FAD and reduced them to NADH2 and FADH2.
- These reduced coenzymes then donate a pair of electrons to a specialized set of electron carriers i.e FAD, NAD, FMN, Coenzyme Q, and Cytochromes (b, c1, c, a+a3), and become oxidized thus reducing the next member of the ETC. Electron Transport Chain is therefore the best example of the Redox Phenomenon because reduction and oxidation is taking place side by side.
- As electrons passed down the ETC, they lose much of their free energy. Part of this energy is captured and stored in the form of ATP and the rest is released as heat. ATP is produced by the phosphorylation of ADP and Pi. This Phosphorylation is coupled with the oxidation and reduction of the members of ETC, therefore this whole process is also known as Oxidative Phosphorylation.
- Each carrier of the ETC can receive electrons from an electron donor and can subsequently donate electrons to the next carrier in the chain, ultimately combining with 1/2 Molecular O2 (Oxygen) and Protons to form water. This requirement of O2 makes the ETC, the Respiratory Chain, which accounts for the greatest portion of the body's utilization of Oxygen.
Site of ETC
- ETC is present The site for the electron transport chain is the inner membrane of the mitochondria in eukaryotic cells and the plasma membrane in prokaryotic cells.
- It is the common final pathway by which electrons, derived from different body fuels, flow to Oxygen.
- Electron Transport and ATP synthesis by Oxidative Phosphorylation proceed continuously in all cells of the body that contain mitochondria.
a. Regarding the Mitochondria
- The outer mitochondrial membrane is permeable to most ions and small molecules.
- The inner mitochondrial membrane is impermeable to most of the small ions including H+, Na+, and K+, and small molecules such as ATP, ADP, Pyruvate, etc.
- Specialized carriers or Transport Systems are required to move ions or molecules across the inner mitochondrial membrane.
b. ATP Synthase Complex
- These are protein complexes attached to the inner surface of the mitochondrial membrane.
- They appear as spheres protruding into the mitochondrial matrix.
- They catalyze ATP-Pi and ATP-ADP exchange reactions.
c. Matrix of mitochondria
- It is a gel-like solution in the interior of the mitochondria.
- It contains the enzymes responsible for the oxidation of Pyruvate, Amino Acids, Fatty Acids (Beta-Oxidation), and those of the Citric Acid Cycle.
- The synthesis of Urea and heme occur partially in the mitochondria.
- The mitochondrial matrix contains electron transport chain to produce ATP.
Arrangement of ETC
- The electron transport chain (ETC) present on the inner mitochondrial membrane is arranged in a sequence i.e. NAD and FAD, FMN, Coenzyme Q, and Cytochromes (b, c1, a+a3), and they are divided into five separate enzyme complexes.
- The complexes are I, II, III, IV, and V.
- Complexes I to IV each contain part of the ETC.
- Complex V catalyzes the ATP synthesis through ATP Synthase Complex.
- Complex I include NADH2, NAD, FMN, and FMNH2.
- Complex II includes FAD, FADH2, and substrate (e.g. Succinate, which reduces FAD to FADH2.)
- Complex III includes Cytochrome "b" (reduced and oxidized form).
- Complex IV includes cytochrome "a+a3" (reduced and oxidized form).
Steps of ETC
- A family of Oxidoreductases especially Dehydrogenases remove two Hydrogen atoms from the substrate.
- Both electrons, but only one proton i.e. a Hydrogen Ion (H+) are transferred to NAD forming NADH plus a free proton (H+) which is released into the mitochondrial matrix.
- The free proton plus the Hydride ion carried by NADH are next transferred to FMN. The NADH gets oxidized and becomes NAD.
- FMN accepts the two hydrogen atoms (2e- plus 2H+) and gets reduced to FMNH2.
- From FMNH2 the hydrogen atoms are transferred to the next member of the chain i.e. Coenzyme Q.
- Coenzyme, also known as Ubiquinone, accepts hydrogen atoms both from FMNH2 and FADH2, which is produced by Succinate Dehydrogenase, and Acyl CoA Dehydrogenase.
- Electrons are next passed from Coenzyme Q to the remaining members of the chain i.e. Cytochrome b, c1, c, a+a3. Each cytochrome contains a heme group made up of a Porphyrin ring containing an iron atom.
- The iron in cytochrome is reversibly converted from Ferric (Fe+++) to it Ferrous (Fe++) form as a part of normal function and as a reversible carrier of electrons.
- Cytochrome a+a3, also known as Cytochrome Oxidase, is the only electron carrier that can react directly with molecular Oxygen. At this site, the transported electrons, free protons, and half-molecular oxygen are brought together to form water.
Production of Free energy during the ETC process
- Free energy is produced as electrons are transferred from an electron donor (reductant or reducing agent) to an electron acceptor (oxidant or oxidizing agent).
- The electrons are transferred in different forms e.g. Hydride Ions (H-) to NAD, as Hydrogen atoms to FMN, FAD, Coenzyme Q, and as electrons (e-) to Cytochrome.
- Energy is released during every transfer of electrons from one electron carrier to another, but this energy is released as free energy. To capture this free energy in the form of ATP, a specific proton gradient is required to Phosphorylate 1 ADP with 1Pi to form 1 ATP.
- There are only three sites at which this required proton gradient is generated and ATPs are synthesized i.e. when electrons jump or transfer from
- NADH to FMN
- Cytochrome "b" to Cytochrome "c1"
- Cytochrome "a" to Cytochrome "a3"
- NADH produces 3ATPs from 3ADPs and 3Pi and FADH2 produces 2ATPs from 2ADPs and 2Pi.
Calculation of energy produced and captured
- The transported electrons from NADH to Oxygen through the electron transport chain produce 52580 Calories.
- 1 ATP produces 7300 Calories.
- 3 ATPs produce 7300 x 3 = 21900 Calories.
- Total Calories produced - Calories stored in the form of ATP (52580 - 21900) = 30680 Calories.
- 30680 Calories are released as heat and help in the thermodynamic control of the human body.
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