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Electron Transport Chain (ETC)

The electron transport chain (ETC) sends electrons through a series of proteins Proteins Linear polypeptides that are synthesized on ribosomes and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of amino acids determines the shape the polypeptide will take, during protein folding, and the function of the protein. Energy Homeostasis, which generate an electrochemical proton gradient that produces energy in the form of adenosine Adenosine A nucleoside that is composed of adenine and d-ribose. Adenosine or adenosine derivatives play many important biological roles in addition to being components of DNA and RNA. Adenosine itself is a neurotransmitter. Class 5 Antiarrhythmic Drugs triphosphate (ATP). Proteins Proteins Linear polypeptides that are synthesized on ribosomes and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of amino acids determines the shape the polypeptide will take, during protein folding, and the function of the protein. Energy Homeostasis generate energy through redox reactions that create the proton gradient. The complete aerobic catabolism of 1 molecule of glucose Glucose A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement. Lactose Intolerance yields between 36 and 38 ATPs, mostly through energy obtained as the reduced coenzymes Coenzymes Small molecules that are required for the catalytic function of enzymes. Many vitamins are coenzymes. Basics of Enzymes NADH and FADH2 are conveyed through the electron transport system. Three of the 4 respiratory complexes that make up the mitochondrial respiratory chain, as well as ATP synthase, are embedded in the inner mitochondrial membrane. Coenzyme Q and cytochrome c transfer electrons between complexes, which will ultimately meet oxygen and generate H2O.

Last updated: Jun 19, 2022

Editorial responsibility: Stanley Oiseth, Lindsay Jones, Evelin Maza

Structure of Mitochondria

  • Mitochondria Mitochondria Semiautonomous, self-reproducing organelles that occur in the cytoplasm of all cells of most, but not all, eukaryotes. Each mitochondrion is surrounded by a double limiting membrane. The inner membrane is highly invaginated, and its projections are called cristae. Mitochondria are the sites of the reactions of oxidative phosphorylation, which result in the formation of ATP. They contain distinctive ribosomes, transfer RNAs; amino Acyl tRNA synthetases; and elongation and termination factors. Mitochondria depend upon genes within the nucleus of the cells in which they reside for many essential messenger RNAs. Mitochondria are believed to have arisen from aerobic bacteria that established a symbiotic relationship with primitive protoeukaryotes. The Cell: Organelles
    • Double-membraned organelles Organelles A cell is a complex unit that performs several complex functions. An organelle is a specialized subunit within a cell that fulfills a specific role or function. Organelles are enclosed within their own lipid bilayers or are unbound by membranes. The Cell: Organelles 
    • Generate energy for the cell in the form of adenosine Adenosine A nucleoside that is composed of adenine and d-ribose. Adenosine or adenosine derivatives play many important biological roles in addition to being components of DNA and RNA. Adenosine itself is a neurotransmitter. Class 5 Antiarrhythmic Drugs triphosphate (ATP)
    • Provide important signals for the body and assist in cell differentiation and cell death Cell death Injurious stimuli trigger the process of cellular adaptation, whereby cells respond to withstand the harmful changes in their environment. Overwhelmed adaptive mechanisms lead to cell injury. Mild stimuli produce reversible injury. If the stimulus is severe or persistent, injury becomes irreversible. Apoptosis is programmed cell death, a mechanism with both physiologic and pathologic effects. Cell Injury and Death 
  • Inner and outer membranes surround mitochondria Mitochondria Semiautonomous, self-reproducing organelles that occur in the cytoplasm of all cells of most, but not all, eukaryotes. Each mitochondrion is surrounded by a double limiting membrane. The inner membrane is highly invaginated, and its projections are called cristae. Mitochondria are the sites of the reactions of oxidative phosphorylation, which result in the formation of ATP. They contain distinctive ribosomes, transfer RNAs; amino Acyl tRNA synthetases; and elongation and termination factors. Mitochondria depend upon genes within the nucleus of the cells in which they reside for many essential messenger RNAs. Mitochondria are believed to have arisen from aerobic bacteria that established a symbiotic relationship with primitive protoeukaryotes. The Cell: Organelles:
    • Made up of a phospholipid bilayer and protein
    • Inner membrane: 
      • Houses proteins Proteins Linear polypeptides that are synthesized on ribosomes and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of amino acids determines the shape the polypeptide will take, during protein folding, and the function of the protein. Energy Homeostasis that generate reactions necessary for the ETC (e.g., ATP synthase).
      • Possesses invaginations called cristae, which house respiratory complexes
      • Cristae are infoldings that increase the surface area of the inner membrane and effectively increase the respiratory capability of mitochondria Mitochondria Semiautonomous, self-reproducing organelles that occur in the cytoplasm of all cells of most, but not all, eukaryotes. Each mitochondrion is surrounded by a double limiting membrane. The inner membrane is highly invaginated, and its projections are called cristae. Mitochondria are the sites of the reactions of oxidative phosphorylation, which result in the formation of ATP. They contain distinctive ribosomes, transfer RNAs; amino Acyl tRNA synthetases; and elongation and termination factors. Mitochondria depend upon genes within the nucleus of the cells in which they reside for many essential messenger RNAs. Mitochondria are believed to have arisen from aerobic bacteria that established a symbiotic relationship with primitive protoeukaryotes. The Cell: Organelles.
      • The inner membrane is permeable to O2, CO2, and H2O only.
    • Matrix: space within the inner membrane
      • Home to important proteins Proteins Linear polypeptides that are synthesized on ribosomes and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of amino acids determines the shape the polypeptide will take, during protein folding, and the function of the protein. Energy Homeostasis: enzymes Enzymes Enzymes are complex protein biocatalysts that accelerate chemical reactions without being consumed by them. Due to the body’s constant metabolic needs, the absence of enzymes would make life unsustainable, as reactions would occur too slowly without these molecules. Basics of Enzymes and intermediates of the citric acid cycle Citric acid cycle The citric acid cycle, also known as the tricarboxylic acid (TCA) cycle or the Krebs cycle, is a cyclic set of reactions that occurs in the mitochondrial matrix. The TCA cycle is the continuation of any metabolic pathway that produces pyruvate, which is converted into its main substrate, acetyl-CoA. Citric Acid Cycle and oxidation of pyruvate Pyruvate Derivatives of pyruvic acid, including its salts and esters. Glycolysis
      • Contains the mitochondrial DNA DNA A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine). DNA Types and Structure genome Genome The complete genetic complement contained in the DNA of a set of chromosomes in a human. The length of the human genome is about 3 billion base pairs. Basic Terms of Genetics
      • ADP and inorganic phosphate Phosphate Inorganic salts of phosphoric acid. Electrolytes (Pi) are specifically transported into the matrix as newly synthesized ATP is transported out.
    • Outer membrane: contains porins that permit diffusion Diffusion The tendency of a gas or solute to pass from a point of higher pressure or concentration to a point of lower pressure or concentration and to distribute itself throughout the available space. Diffusion, especially facilitated diffusion, is a major mechanism of biological transport. Peritoneal Dialysis and Hemodialysis of ions and metabolites
      • Passage of metabolites, such as ATP, ADP, calcium Calcium A basic element found in nearly all tissues. It is a member of the alkaline earth family of metals with the atomic symbol ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. Electrolytes ion ( Ca CA Condylomata acuminata are a clinical manifestation of genital HPV infection. Condylomata acuminata are described as raised, pearly, flesh-colored, papular, cauliflower-like lesions seen in the anogenital region that may cause itching, pain, or bleeding. Condylomata Acuminata (Genital Warts)2+), and phosphate Phosphate Inorganic salts of phosphoric acid. Electrolytes is a process mediated by transport proteins Proteins Linear polypeptides that are synthesized on ribosomes and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of amino acids determines the shape the polypeptide will take, during protein folding, and the function of the protein. Energy Homeostasis:
        • Stores voltage-dependent anion channels Channels The Cell: Cell Membrane, which allow for the transit of nucleotides Nucleotides The monomeric units from which DNA or RNA polymers are constructed. They consist of a purine or pyrimidine base, a pentose sugar, and a phosphate group. Nucleic Acids and ions
        • Permits the generation of ion gradients
      • Specific transporters carry pyruvate Pyruvate Derivatives of pyruvic acid, including its salts and esters. Glycolysis, fatty acids Acids Chemical compounds which yield hydrogen ions or protons when dissolved in water, whose hydrogen can be replaced by metals or basic radicals, or which react with bases to form salts and water (neutralization). An extension of the term includes substances dissolved in media other than water. Acid-Base Balance, and amino acids Amino acids Organic compounds that generally contain an amino (-NH2) and a carboxyl (-COOH) group. Twenty alpha-amino acids are the subunits which are polymerized to form proteins. Basics of Amino Acids or their alpha-keto derivatives into the matrix for access to the machinery of the citric acid cycle Citric acid cycle The citric acid cycle, also known as the tricarboxylic acid (TCA) cycle or the Krebs cycle, is a cyclic set of reactions that occurs in the mitochondrial matrix. The TCA cycle is the continuation of any metabolic pathway that produces pyruvate, which is converted into its main substrate, acetyl-CoA. Citric Acid Cycle.
    • Intermembrane space: between the outer and inner membranes
      • Contains the same small molecules that are present in the cytosol Cytosol A cell’s cytoskeleton is a network of intracellular protein fibers that provides structural support, anchors organelles, and aids intra- and extracellular movement. The Cell: Cytosol and Cytoskeleton
      • Controlled region with different larger proteins Proteins Linear polypeptides that are synthesized on ribosomes and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of amino acids determines the shape the polypeptide will take, during protein folding, and the function of the protein. Energy Homeostasis that are regulated by the outer membrane
Anatomy of mitochondrion

Anatomy of the mitochondrion:
The important structures of the mitochondrion include the outer membrane, intermembrane space, inner membrane, and matrix.

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Complexes of the ETC

Complex I

  • NADH: ubiquinone oxidoreductase
  • The enzyme complex moves 2 electrons from NADH to a carrier Carrier Vaccination (ubiquinone) through a redox reaction that translocates 4 protons.
  • The protons are pumped from the matrix to the intermembrane space.

Complex II

  • Succinate dehydrogenase Succinate dehydrogenase A flavoprotein containing oxidoreductase that catalyzes the dehydrogenation of succinate to fumarate. In most eukaryotic organisms this enzyme is a component of mitochondrial electron transport complex II. Citric Acid Cycle
  • Delivers electrons for the quinone Quinone A lipid cofactor that is required for normal blood clotting. Several forms of vitamin K have been identified: vitamin K 1 (phytomenadione) derived from plants, vitamin K 2 (menaquinone) from bacteria, and synthetic naphthoquinone provitamins, vitamin K 3 (menadione). Vitamin k 3 provitamins, after being alkylated in vivo, exhibit the antifibrinolytic activity of vitamin k. Green leafy vegetables, liver, cheese, butter, and egg yolk are good sources of vitamin k. Fat-soluble Vitamins and their Deficiencies pool
  • Transfers FAD to quinone Quinone A lipid cofactor that is required for normal blood clotting. Several forms of vitamin K have been identified: vitamin K 1 (phytomenadione) derived from plants, vitamin K 2 (menaquinone) from bacteria, and synthetic naphthoquinone provitamins, vitamin K 3 (menadione). Vitamin k 3 provitamins, after being alkylated in vivo, exhibit the antifibrinolytic activity of vitamin k. Green leafy vegetables, liver, cheese, butter, and egg yolk are good sources of vitamin k. Fat-soluble Vitamins and their Deficiencies

Complex III

  • Coenzyme Q-cytochrome c reductase
  • 4 protons translocated to the intermembrane space
  • Complex inhibited by dimercaprol Dimercaprol An anti-gas warfare agent that is effective against lewisite (dichloro(2-chlorovinyl)arsine) and formerly known as british anti-lewisite or bal. It acts as a chelating agent and is used in the treatment of arsenic, gold, and other heavy metal poisoning. Metal Poisoning (Lead, Arsenic, Iron)

Complex IV Complex IV Cyanide Poisoning

  • Cytochrome c oxidase Oxidase Neisseria
  • 4 electrons transfer to O2 and produce 2 molecules of H2O.
  • 8 protons added to the proton gradient 

Electron Transport

  • Inner mitochondrial membrane:
    • Mostly impermeable to molecules and ions such as hydrogen ions (H+)
    • Separates the intermediates and enzymes Enzymes Enzymes are complex protein biocatalysts that accelerate chemical reactions without being consumed by them. Due to the body’s constant metabolic needs, the absence of enzymes would make life unsustainable, as reactions would occur too slowly without these molecules. Basics of Enzymes of metabolic pathways of those in the cytosol Cytosol A cell’s cytoskeleton is a network of intracellular protein fibers that provides structural support, anchors organelles, and aids intra- and extracellular movement. The Cell: Cytosol and Cytoskeleton from those occurring in the mitochondrial matrix
    • Plays host to cofactors that were reduced throughout catabolic pathways occurring in different cellular compartments
    • Bears the compartment of the respiratory chain and ATP synthase
  • Mitochondrial matrix:
    • Contains the pyruvate Pyruvate Derivatives of pyruvic acid, including its salts and esters. Glycolysis dehydrogenase complex enzymes Enzymes Enzymes are complex protein biocatalysts that accelerate chemical reactions without being consumed by them. Due to the body’s constant metabolic needs, the absence of enzymes would make life unsustainable, as reactions would occur too slowly without these molecules. Basics of Enzymes 
    • Also contains the citric acid cycle Citric acid cycle The citric acid cycle, also known as the tricarboxylic acid (TCA) cycle or the Krebs cycle, is a cyclic set of reactions that occurs in the mitochondrial matrix. The TCA cycle is the continuation of any metabolic pathway that produces pyruvate, which is converted into its main substrate, acetyl-CoA. Citric Acid Cycle enzymes Enzymes Enzymes are complex protein biocatalysts that accelerate chemical reactions without being consumed by them. Due to the body’s constant metabolic needs, the absence of enzymes would make life unsustainable, as reactions would occur too slowly without these molecules. Basics of Enzymes, the fatty acid beta-oxidation pathway, and other pathways involved in amino acid Amino acid Amino acids (AAs) are composed of a central carbon atom attached to a carboxyl group, an amino group, a hydrogen atom, and a side chain (R group). Basics of Amino Acids oxidation
  • Here, the conveying of electrons through 3 respiratory complexes is coupled to the outward pumping of protons.
Mitochondrial membranes

Mitochondrial membranes:
Key proteins Proteins Linear polypeptides that are synthesized on ribosomes and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of amino acids determines the shape the polypeptide will take, during protein folding, and the function of the protein. Energy Homeostasis are shown within the inner membrane. The citric acid cycle Citric acid cycle The citric acid cycle, also known as the tricarboxylic acid (TCA) cycle or the Krebs cycle, is a cyclic set of reactions that occurs in the mitochondrial matrix. The TCA cycle is the continuation of any metabolic pathway that produces pyruvate, which is converted into its main substrate, acetyl-CoA. Citric Acid Cycle is crucial to the process, as it provides NADH for the electron transport chain (ETC).

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Oxidative Phosphorylation

  • The ETC is linked to oxidative phosphorylation Phosphorylation The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety. Post-translational Protein Processing through the proton gradient.
  • ATP synthase harnesses the proton gradient through oxidative phosphorylation Phosphorylation The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety. Post-translational Protein Processing to generate ATP:
    • ATP synthase functions as an ion channel for protons to return to the mitochondrial matrix.
    • Energy is generated by the flow Flow Blood flows through the heart, arteries, capillaries, and veins in a closed, continuous circuit. Flow is the movement of volume per unit of time. Flow is affected by the pressure gradient and the resistance fluid encounters between 2 points. Vascular resistance is the opposition to flow, which is caused primarily by blood friction against vessel walls. Vascular Resistance, Flow, and Mean Arterial Pressure of protons, which is used for ATP synthesis Synthesis Polymerase Chain Reaction (PCR).
  • There are numerous ways to generate ATP: 
    • Glycolysis Glycolysis Glycolysis is a central metabolic pathway responsible for the breakdown of glucose and plays a vital role in generating free energy for the cell and metabolites for further oxidative degradation. Glucose primarily becomes available in the blood as a result of glycogen breakdown or from its synthesis from noncarbohydrate precursors (gluconeogenesis) and is imported into cells by specific transport proteins. Glycolysis:
      • 2 ATP are produced during glycolysis Glycolysis Glycolysis is a central metabolic pathway responsible for the breakdown of glucose and plays a vital role in generating free energy for the cell and metabolites for further oxidative degradation. Glucose primarily becomes available in the blood as a result of glycogen breakdown or from its synthesis from noncarbohydrate precursors (gluconeogenesis) and is imported into cells by specific transport proteins. Glycolysis.
      • 2 NAD NAD+ A coenzyme composed of ribosylnicotinamide 5′-diphosphate coupled to adenosine 5′-phosphate by pyrophosphate linkage. It is found widely in nature and is involved in numerous enzymatic reactions in which it serves as an electron carrier by being alternately oxidized (NAD+) and reduced (NADH). Pentose Phosphate Pathway+ are reduced to NADH.
      • 2 pyruvate Pyruvate Derivatives of pyruvic acid, including its salts and esters. Glycolysis molecules are then used to produce 2 Acetyl-CoA Acetyl-CoA Acetyl CoA participates in the biosynthesis of fatty acids and sterols, in the oxidation of fatty acids and in the metabolism of many amino acids. It also acts as a biological acetylating agent. Citric Acid Cycle molecules by pyruvate Pyruvate Derivatives of pyruvic acid, including its salts and esters. Glycolysis dehydrogenase, which produces 1 NADH each.
      • 2 Acetyl-CoA Acetyl-CoA Acetyl CoA participates in the biosynthesis of fatty acids and sterols, in the oxidation of fatty acids and in the metabolism of many amino acids. It also acts as a biological acetylating agent. Citric Acid Cycle molecules enter the citric acid cycle Citric acid cycle The citric acid cycle, also known as the tricarboxylic acid (TCA) cycle or the Krebs cycle, is a cyclic set of reactions that occurs in the mitochondrial matrix. The TCA cycle is the continuation of any metabolic pathway that produces pyruvate, which is converted into its main substrate, acetyl-CoA. Citric Acid Cycle, where they condense with oxaloacetate Oxaloacetate Derivatives of oxaloacetic acid. Included under this heading are a broad variety of acid forms, salts, esters, and amides that include a 2-keto-1, 4-carboxy aliphatic structure. Citric Acid Cycle and generate:
        • 2 guanosine triphosphates (GTP), which are converted to 2 ATPs
        • 6 NADH
        • 2 FADH2
  • The ETC is crucial for setting up the proton gradient:
    • Each NADH enters the electron transport chain at complex I, where it is reoxidized and passes its electrons to CoQ.
    • Electrons flow Flow Blood flows through the heart, arteries, capillaries, and veins in a closed, continuous circuit. Flow is the movement of volume per unit of time. Flow is affected by the pressure gradient and the resistance fluid encounters between 2 points. Vascular resistance is the opposition to flow, which is caused primarily by blood friction against vessel walls. Vascular Resistance, Flow, and Mean Arterial Pressure from CoQ to complex III, which relays them through cytochrome c to complex IV Complex IV Cyanide Poisoning.
    • Here, they are accepted by O2.
    • Both complex I and complex III convey 4 protons each into the intermembrane space, whereas complex IV Complex IV Cyanide Poisoning pumps 2 into the intermembrane space per pair of electrons.
    • 6 NADH produced during the citric acid cycle Citric acid cycle The citric acid cycle, also known as the tricarboxylic acid (TCA) cycle or the Krebs cycle, is a cyclic set of reactions that occurs in the mitochondrial matrix. The TCA cycle is the continuation of any metabolic pathway that produces pyruvate, which is converted into its main substrate, acetyl-CoA. Citric Acid Cycle yield 60 protons in the intermembrane space.
  • 2 ATP generated during glycolysis Glycolysis Glycolysis is a central metabolic pathway responsible for the breakdown of glucose and plays a vital role in generating free energy for the cell and metabolites for further oxidative degradation. Glucose primarily becomes available in the blood as a result of glycogen breakdown or from its synthesis from noncarbohydrate precursors (gluconeogenesis) and is imported into cells by specific transport proteins. Glycolysis and 2 produced in the citric acid cycle Citric acid cycle The citric acid cycle, also known as the tricarboxylic acid (TCA) cycle or the Krebs cycle, is a cyclic set of reactions that occurs in the mitochondrial matrix. The TCA cycle is the continuation of any metabolic pathway that produces pyruvate, which is converted into its main substrate, acetyl-CoA. Citric Acid Cycle
Table: Protons conveyed into the intermembrane space as a result of oxidation of 1 molecule of palmitoyl-CoA to CO2 and H2
Enzyme catalyzing oxidation step Number of NADH or FADH2 formed Number of protons ultimately translocated into intermembrane space
Acyl-CoA dehydrogenase Acyl-CoA dehydrogenase A flavoprotein oxidoreductase that has specificity for medium-chain fatty acids. It forms a complex with electron transferring flavoproteins and conveys reducing equivalents to ubiquinone. Fatty Acid Metabolism 7 FADH2 42
Beta-hydroxyacyl-CoA dehydrogenase 7 NADH 70
Isocitrate dehydrogenase Isocitrate dehydrogenase An enzyme of the oxidoreductase class that catalyzes the conversion of isocitrate and NAD+ to yield 2-ketoglutarate, carbon dioxide, and nadh. It occurs in cell mitochondria. The enzyme requires mg2+, mn2+; it is activated by adp, citrate, and Ca2+, and inhibited by nadh, NADPH, and ATP. The reaction is the key rate-limiting step of the citric acid (tricarboxylic) cycle. Citric Acid Cycle 8 NADH 80
Alpha-ketoglutarate dehydrogenase 8 NADH 80
Succinate dehydrogenase Succinate dehydrogenase A flavoprotein containing oxidoreductase that catalyzes the dehydrogenation of succinate to fumarate. In most eukaryotic organisms this enzyme is a component of mitochondrial electron transport complex II. Citric Acid Cycle 8 FADH2 48
Malate dehydrogenase 8 NADH 80
Total 400

Control of Oxidative Phosphorylation

  • Important regulation mechanisms exist to control the rate of glycolysis Glycolysis Glycolysis is a central metabolic pathway responsible for the breakdown of glucose and plays a vital role in generating free energy for the cell and metabolites for further oxidative degradation. Glucose primarily becomes available in the blood as a result of glycogen breakdown or from its synthesis from noncarbohydrate precursors (gluconeogenesis) and is imported into cells by specific transport proteins. Glycolysis, the citric acid cycle Citric acid cycle The citric acid cycle, also known as the tricarboxylic acid (TCA) cycle or the Krebs cycle, is a cyclic set of reactions that occurs in the mitochondrial matrix. The TCA cycle is the continuation of any metabolic pathway that produces pyruvate, which is converted into its main substrate, acetyl-CoA. Citric Acid Cycle, pyruvate Pyruvate Derivatives of pyruvic acid, including its salts and esters. Glycolysis oxidation, and oxidative phosphorylation Phosphorylation The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety. Post-translational Protein Processing by the relative concentrations: 
    • ATP
    • ADP
    • AMP
    • NADH
  • Glycolysis Glycolysis Glycolysis is a central metabolic pathway responsible for the breakdown of glucose and plays a vital role in generating free energy for the cell and metabolites for further oxidative degradation. Glucose primarily becomes available in the blood as a result of glycogen breakdown or from its synthesis from noncarbohydrate precursors (gluconeogenesis) and is imported into cells by specific transport proteins. Glycolysis, fatty acid degradation, and the citric acid cycle Citric acid cycle The citric acid cycle, also known as the tricarboxylic acid (TCA) cycle or the Krebs cycle, is a cyclic set of reactions that occurs in the mitochondrial matrix. The TCA cycle is the continuation of any metabolic pathway that produces pyruvate, which is converted into its main substrate, acetyl-CoA. Citric Acid Cycle provide the primary sources of electrons that enter the mitochondrial ETC.
  • Control of glycolysis Glycolysis Glycolysis is a central metabolic pathway responsible for the breakdown of glucose and plays a vital role in generating free energy for the cell and metabolites for further oxidative degradation. Glucose primarily becomes available in the blood as a result of glycogen breakdown or from its synthesis from noncarbohydrate precursors (gluconeogenesis) and is imported into cells by specific transport proteins. Glycolysis and the citric acid cycle Citric acid cycle The citric acid cycle, also known as the tricarboxylic acid (TCA) cycle or the Krebs cycle, is a cyclic set of reactions that occurs in the mitochondrial matrix. The TCA cycle is the continuation of any metabolic pathway that produces pyruvate, which is converted into its main substrate, acetyl-CoA. Citric Acid Cycle is coordinated with the demand for oxidative phosphorylation Phosphorylation The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety. Post-translational Protein Processing.
  • Oxidative phosphorylation Phosphorylation The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety. Post-translational Protein Processing is maintained by cellular energy requirements:
    • Intracellular ADP and the ATP are measures of a cell’s energy status.
    • An adequate supply of electrons to feed the electron transport chain is provided by regulation of the control points of glycolysis Glycolysis Glycolysis is a central metabolic pathway responsible for the breakdown of glucose and plays a vital role in generating free energy for the cell and metabolites for further oxidative degradation. Glucose primarily becomes available in the blood as a result of glycogen breakdown or from its synthesis from noncarbohydrate precursors (gluconeogenesis) and is imported into cells by specific transport proteins. Glycolysis and the citric acid cycle Citric acid cycle The citric acid cycle, also known as the tricarboxylic acid (TCA) cycle or the Krebs cycle, is a cyclic set of reactions that occurs in the mitochondrial matrix. The TCA cycle is the continuation of any metabolic pathway that produces pyruvate, which is converted into its main substrate, acetyl-CoA. Citric Acid Cycle by NADH and metabolites:
      • Phosphofructokinase (PFK)
      • Pyruvate Pyruvate Derivatives of pyruvic acid, including its salts and esters. Glycolysis dehydrogenase
      • Citrate synthase Citrate synthase Enzyme that catalyzes the first step of the tricarboxylic acid cycle (citric acid cycle). It catalyzes the reaction of oxaloacetate and acetyl CoA to form citrate and coenzyme a. Citric Acid Cycle
      • Isocitrate dehydrogenase Isocitrate dehydrogenase An enzyme of the oxidoreductase class that catalyzes the conversion of isocitrate and NAD+ to yield 2-ketoglutarate, carbon dioxide, and nadh. It occurs in cell mitochondria. The enzyme requires mg2+, mn2+; it is activated by adp, citrate, and Ca2+, and inhibited by nadh, NADPH, and ATP. The reaction is the key rate-limiting step of the citric acid (tricarboxylic) cycle. Citric Acid Cycle (IDH)
      • Alpha-ketoglutarate dehydrogenase
  • Interlocking of the citric acid cycle Citric acid cycle The citric acid cycle, also known as the tricarboxylic acid (TCA) cycle or the Krebs cycle, is a cyclic set of reactions that occurs in the mitochondrial matrix. The TCA cycle is the continuation of any metabolic pathway that produces pyruvate, which is converted into its main substrate, acetyl-CoA. Citric Acid Cycle and glycolysis Glycolysis Glycolysis is a central metabolic pathway responsible for the breakdown of glucose and plays a vital role in generating free energy for the cell and metabolites for further oxidative degradation. Glucose primarily becomes available in the blood as a result of glycogen breakdown or from its synthesis from noncarbohydrate precursors (gluconeogenesis) and is imported into cells by specific transport proteins. Glycolysis by citrate, which hinders glycolysis Glycolysis Glycolysis is a central metabolic pathway responsible for the breakdown of glucose and plays a vital role in generating free energy for the cell and metabolites for further oxidative degradation. Glucose primarily becomes available in the blood as a result of glycogen breakdown or from its synthesis from noncarbohydrate precursors (gluconeogenesis) and is imported into cells by specific transport proteins. Glycolysis, facilitates the mode of action of the adenine Adenine A purine base and a fundamental unit of adenine nucleotides. Nucleic Acids nucleotide system:
    • Increased levels of NADH and acetyl-CoA Acetyl-CoA Acetyl CoA participates in the biosynthesis of fatty acids and sterols, in the oxidation of fatty acids and in the metabolism of many amino acids. It also acts as a biological acetylating agent. Citric Acid Cycle hinders the oxidation of pyruvate Pyruvate Derivatives of pyruvic acid, including its salts and esters. Glycolysis to acetyl-CoA Acetyl-CoA Acetyl CoA participates in the biosynthesis of fatty acids and sterols, in the oxidation of fatty acids and in the metabolism of many amino acids. It also acts as a biological acetylating agent. Citric Acid Cycle.
    • A high NADH/ NAD NAD+ A coenzyme composed of ribosylnicotinamide 5′-diphosphate coupled to adenosine 5′-phosphate by pyrophosphate linkage. It is found widely in nature and is involved in numerous enzymatic reactions in which it serves as an electron carrier by being alternately oxidized (NAD+) and reduced (NADH). Pentose Phosphate Pathway+ ratio hinders the dehydrogenase reactions of the citric acid cycle Citric acid cycle The citric acid cycle, also known as the tricarboxylic acid (TCA) cycle or the Krebs cycle, is a cyclic set of reactions that occurs in the mitochondrial matrix. The TCA cycle is the continuation of any metabolic pathway that produces pyruvate, which is converted into its main substrate, acetyl-CoA. Citric Acid Cycle.
  • Another important regulatory effect is the inhibition of PFK by citrate:
    • When the demand for ATP decreases, ATP increases and ADP decreases.
    • Because ADP activates IDH and ATP inhibits alpha-ketoglutarate dehydrogenase, the citric acid cycle Citric acid cycle The citric acid cycle, also known as the tricarboxylic acid (TCA) cycle or the Krebs cycle, is a cyclic set of reactions that occurs in the mitochondrial matrix. The TCA cycle is the continuation of any metabolic pathway that produces pyruvate, which is converted into its main substrate, acetyl-CoA. Citric Acid Cycle slows down.
    • The slow-down causes the citrate concentration to build up.
    • Citrate leaves the mitochondria Mitochondria Semiautonomous, self-reproducing organelles that occur in the cytoplasm of all cells of most, but not all, eukaryotes. Each mitochondrion is surrounded by a double limiting membrane. The inner membrane is highly invaginated, and its projections are called cristae. Mitochondria are the sites of the reactions of oxidative phosphorylation, which result in the formation of ATP. They contain distinctive ribosomes, transfer RNAs; amino Acyl tRNA synthetases; and elongation and termination factors. Mitochondria depend upon genes within the nucleus of the cells in which they reside for many essential messenger RNAs. Mitochondria are believed to have arisen from aerobic bacteria that established a symbiotic relationship with primitive protoeukaryotes. The Cell: Organelles via a specific transport system and, once in the cytosol Cytosol A cell’s cytoskeleton is a network of intracellular protein fibers that provides structural support, anchors organelles, and aids intra- and extracellular movement. The Cell: Cytosol and Cytoskeleton, acts to restrain carbohydrate breakdown by inhibiting PFK.

References

  1. Ahmad, M, Woiberg, A, Kahwaji, CI. (2020). Biochemistry, electron transport chain. StatPearls. Retrieved May 26, 2021, from https://www.ncbi.nlm.nih.gov/books/NBK526105/
  2. Cooper, GM. (2000). The mechanism of oxidative phosphorylation. The Cell: A Molecular Approach. 2nd edition. Sunderland (MA): Sinauer Associates. https://www.ncbi.nlm.nih.gov/books/NBK9885/
  3. Alberts, B, Johnson, A, Lewis, J, et al. (2002). Electron-transport chains and their proton pumps. Molecular Biology of the Cell. 4th edition. New York: Garland Science. https://www.ncbi.nlm.nih.gov/books/NBK26904/

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