Chapter 18- Electron Transport Chain Flashcards
Electron transport chain
In oxidative phosphorylation, electrons flow from NADH and FADH2 to oxygen. This electron flow takes place in 4 large protein complexes that are embedded in the inner mitochondrial membrane. The reactions take place on the matrix side of the membrane. The complexes are called the electron transport chain or the respiratory chain. There is a combined, sequential set of redox reactions that occur in the protein complexes
Overall reaction mechanism of the ETC
The overall reaction is exergonic. 3 of the complexes of the ETC use the energy released by the electron flow to pump protons out of the mitochondrial matrix. Energy is transformed in this reaction. The resulting unequal distribution of protons generates a proton-motive force.
Proton-motive force
The energy-rich unequal distribution of protons. Generated by the unequal distribution of protons across the inner mitochondrial membrane. This proton gradient is used for ATP synthesis- ATP is synthesized when protons flow back to the mitochondrial matrix through an enzyme complex (chemiosmosis)
Oxidative phosphorylation
The pathway that recycles ATP. The oxidation of fuels and the phosphorylation of ADP are coupled by a proton gradient across the inner mitochondrial membrane
Chemiosmotic hypothesis
The idea that electron transport and ATP synthesis are coupled by a proton gradient across the inner mitochondrial membrane. The transfer of electrons through the respiratory chain leads to the pumping of protons from the matrix to the intermembrane space. The hydrogen ion (H+) concentration becomes lower in the matrix, and an electric charge with the matrix side being negative is negative is generated. Then, protons flow back into the matrix to equalize this distribution. This flow of protons drives the synthesis of ATP by ATP synthase
2 components of the proton motive force
A chemical gradient and a charge gradient. The chemical gradient is represented as a pH gradient. The charge gradient is created by the positive charge on the unequally distributed protons forming the chemical gradient. Both of these components power the synthesis of ATP.
Chemiosmosis
The movement of protons down the concentration gradient- from high H+ concentration to low H+ concentration. This movement of protons synthesizes ATP. The proton gradient is established across the inner mitochondrial membrane
Flow of protons across the inner mitochondrial membrane
Proton gradient is initiated by outward pumping of H+ from the mitochondrial matrix by three large protein complexes. The inward flow of H+ through the membrane-bound ATP
synthase protein accomplishes ATP synthesis.
Which redox reactions occur in the electron transport chain?
NADH is oxidized to form NAD+. Oxygen is also reduced to form water
What is the driving force of oxidative phosphorylation?
The electron transfer potential of NADH or FADH2 relative to that of oxygen. Electrons are transferred from NADH to oxygen through the ETC protein complexes
Proteins of the ETC (4)
- NADH-Q oxidoreductase (complex 1)
- Q-cytochrome c oxidoreductase (complex 3)
- Cytochrome c oxidase (complex 4)
- Succinate-Q reductase (complex 2)
Function of complexes 1, 3, and 4
Electron flow in these complexes is highly exergonic and powers the transport of protons across the inner mitochondrial membrane. These complexes are associated in a supramolecular complex, which facilitates the rapid transfer of substrate and prevents the release of reaction intermediates
Succinate-Q reductase (complex 2)
Contains the succinate dehydrogenase that generates FADH2 in the citric acid cycle. Electrons from this FADH2 enter the ETC at complex 3. Succinate-Q reductase is different from the other complexes because it does not pump protons
Coenzyme Q (Q)
An electron carrier- also called ubiquinone because it’s a ubiquitous quinone in biological systems. It is a hydrophobic quinone that diffuses rapidly within the inner mitochondrial membrane. Electrons are carried from complex 1 to complex 3 by the reduced form of Q. 2 electrons from the FADH2 generated by the citric acid cycle are transferred first to Q and then to complex 3. Q is also an entry point for 2 electrons from fatty acid oxidation and glycerol-3-phosphate dehydrogenase
F1F0 ATPase (ATP synthase)
Also called complex 5- it is a molecular assembly in the inner mitochondrial membrane that carries out the synthesis of ATP. The oxidation of NADH is coupled to the phosphorylation of ADP through a proton gradient across the inner mitochondrial membrane
Proton circuit
There is a circuit of protons across the inner mitochondrial membrane. Protons pass through ATP synthase to get to the outer space of the mitochondria and make ATP. They enter the intermembrane space from the outer membrane by passing through the ETC. The ETC acts like the “battery” for the circuit. The “capacitor” (energy storage) is the proton gradient. The resistor is ATP synthase- regulates the flow of current
Uncoupling of oxidative phosphorylation
Uncoupling means that ATP synthesis no longer occurs. Uncoupling causes proton “leakage” and production of heat. In animals, the uncoupling is in brown adipose tissue, which is specialized tissue for the process of nonshivering thermogenesis
Brown adipose tissue
Very rich in mitochondria- the tissue appears brown from the combination of the greenish-colored cytochromes in the numerous mitochondria and the red hemoglobin present in the extensive blood supply. There are smaller fat droplets that leave more space for mitochondria. This helps to carry heat through the body. The inner mitochondrial membrane of these mitochondria contain a large amount of uncoupling protein (UCP-1).
Uncoupling protein (thermogenin)
Located in the inner mitochondrial membranes of the mitochondria in brown adipose tissue. UCP-1 transports protons from the intermembrane space to the matrix with the assistance of fatty acids. UCP-1 generates heat by “short circuiting” the mitochondrial proton battery. The energy of the proton gradient is normally captured as ATP, but in this case it is released as heat as the protons flow through UCP-1. The heat is generated (thermogenesis) since ATP production is reduced. This dissipative proton pathway is activated when the core body temperature begins to fall.
2,4-dinitrophenol (DNP)
The uncoupling of the ETC and phosphorylation in the mitochondria can be accomplished by DNP. This inhibits oxidative phosphorylation. In the presence of uncouplers, electron transport from NADH to oxygen proceeds in a normal fashion, but ATP is not formed by mitochondrial ATP synthase. This is because the proton motive force across the inner mitochondrial membrane is continuously dissipated
Consequences of uncoupling
The loss of respiratory control leads to increased oxygen consumption and oxidation of NADH. Energy is not captured as ATP- it is released as heat. The effects of oligomycin further illustrate that electron transport and ATP synthesis are tightly coupled under normal conditions
Oligomycin
An antibiotic used as an antifungal agent. It prevents the influx of protons through ATP synthase by binding to the carboxylate group of the c subunits required for proton binding. If respiring mitochondria are exposed to an inhibitor of ATP synthase, the ETC stops operating and ATP synthesis is prevented
Structure of the mitochondria
The mitochondria contains an outer membrane and an inner membrane. The inner membrane forms folds called cristae. The space between the 2 membranes is called the intermembrane space. The mitochondrial matrix is the space within the inner membrane
Complexes 1-4 structure
Complexes I–IV contain transmembrane regions that are
embedded in the inner mitochondrial membrane as well as functional domains that face toward the mitochondrial matrix
Complex 1
Where NADH oxidation occurs, and coenzyme Q is reduced. Complex 1 is the largest complex and its protein is NADH-Q oxidoreductase. Its prosthetic group is flavin mononucleotide (FMN), which it is covalently bonded to flavin mononucleotide (FMN). Complex 1 is a proton pump that is encoded by genes in the mitochondria and the nucleus
Electron transport system inhibitors (4)
- Rotenone
- Hydrogen cyanide
- Carbon monoxide
- Antimycin A
Inhibition of the ETC also inhibited ATP synthesis since the proton motive force can’t be generated
Rotenone
An ETC inhibitor. It is used as a fish and insect poison. It blocks electron transfer in complex 1 and therefore prevent the use of NADH as a substrate. It may play a role in the development of Parkinson’s disease. In the presence of rotenone, electron flow resulting from the oxidation of succinate is not impaired, because these electrons enter through QH2, beyond the block
Antimycin A
An ETC inhibitor. It interferes with electron flow from cytochrome bH in complex 3.
Cyanide
An ETC inhibitor, blocks electron flow in complex 4. It reacts with the ferric form of heme a3
Carbon monoxide
An ETC inhibitor, blocks electron flow in complex 4. It inhibits the ferrous form of heme a3
Reduction potential/redox potential
The expression for the electron-transfer potential. The electron transfer potential of NADH or FADH2 is converted into the phosphoryl transfer potential of ATP in oxidative phosphorylation. E’0 represents the reduction potential. The free energy change of an oxidation-reduction reaction can be calculated from the reduction potentials of the reactants
Positive and negative reduction potential
A negative reduction potential means that the oxidized form of a substance has lower affinity for electrons than does H2. A positive reduction potential means that the oxidized form of a substance has higher affinity for electrons than does H2. A strong reducing agent like NADH is poised to donate electrons and has a negative reduction potential. A strong oxidizing agent like oxygen is ready to accept electrons and has a positive reduction potential
Q cycle
The mechanism for the coupling of electron transfer from coenzyme Q (source of electrons) to cytochrome c to transmembrane protein transport. The cycle takes place in complex 3. Qh2 passes 2 electrons to complex 3- however, cytochrome c is the acceptor of electrons in complex 3, and it can only accept one electron. The cell must switch from the 2 electron carrier ubiquinol to the one electron carrier, cytochrome c. Ultimately, it converts the 2e– transport system (complexes I and II) to the 2 1e– transport systems in cytochrome c (complex III). Cytochrome c is reduced in this process
Mechanism of the Q cycle
In the first half of the cycle, two electrons of a bound QH2 are transferred, one to cytochrome c and the other to a bound Q in a second binding site. This forms the semiquinone radical anion Q-. The newly formed Q dissociates and enters the Q pool. In the second half of the cycle, a second Qh2 also gives up its electrons to complex 3- one goes to a second molecule of cytochrome c, and the other reduces the Q radical anion to Qh2. The second electron transfer results in the uptake of two protons from the matrix
Redox loops
Separation of protons and electrons on opposite sides of the membrane. The Q cycle in complex 3 is an example. Electrons are transferred from the outside to the inside of the membrane and then co-transported back across the membrane with protons?
Proton pumps
Membrane proteins that have the ability to create and maintain an electrochemical proton gradient by transferring protons from one side of the membrane to the other. They are dependent on protein complex conformational changes. This includes complexes 1, 3, and 4. Complex 2 does not pump protons
Q pool
Ubiquinone (coenzyme Q) is soluble in the membrane, so a pool of Q and Qh2 is thought to exist in the inner mitochondrial membrane
Cytochrome c
A second electron carrier. It is a small soluble protein that shuttles electrons from complex 3 to complex 4- this is the final component in the chain and the one that catalyzes the reduction of oxygen
2 electron carriers that transport electrons between complexes
- Coenzyme Q (Q)
- Cytochrome c
Complex 1 reaction
The initial step is the binding of NADH and the transfer of its two high potential electrons to the flavin mononucleotide (FMN) prosthetic group. This yields the reduced form, FMNH2. Electrons are then transferred from FMNH2 to a series of iron-sulfur clusters, the second type of prosthetic group in complex 1. The reaction uses NADH, Q, 5H+ from the matrix to make NAD+, QH2, and 4 H+ in the intermembrane space
Complex 1 structure
Complex 1 is a large enzyme that consists of 45 polypeptide chains organized into 14 core subunits. It is L shaped, with a horizontal arm lying in the membrane and a vertical arm that projects into the matrix
Flavin mononucleotide reactions
- NADH transfers 2 electrons to FMN
- 2 electrons are transferred from carrier to carrier
- 2 electrons and 2 H+ bind to Q, forming QH2
Occurs in complex 1
Semiquinone
Oxidized flavin mononucleotide (FMN) can be reduced one electron at a time to form a semiquinone intermediate and reduced flavin mononucleotide (FMNH2)
What does coenzyme Q act as an entry point for?
For 2- from the citric acid cycle, fatty acid oxidation, and glycerol-3-phosphate dehydrogenase
Coenzyme Q reduction
Ubiquinone (Q) is reduced to ubiquinol (QH2). 4H+ are translocated from the matrix side of the membrane to the
intermembrane space
Ubiquinol function
Ubiquinol (QH2) is the entry point for electrons from FADH2 of flavoproteins. FADH2 enters the ETC at the second protein complex of the chain, when succinate is oxidized to make fumarate. Succinate dehydrogenase is part of complex 2, and FADH2 does not leave the complex. Its electrons are transferred to Fe-S centers and then finally to Q to form QH2. QH2 is then ready to transfer electrons down the ETC. Once ubiquinol is generated by complexes 1 and 2, the electrons from QH2 are passed to cytochrome c by complex 3.
Complex 2
Succinate-Q reductase complex- its protein is succinate dehydrogenase. It catalyzes the oxidation-reduction of succinate to fumarate (using the succinate dehydrogenase enzyme). It performs coupled redox reaction using FAD- FADH2 transfers its electrons to Q to reduce coenzyme Q to QH2. Then, the electrons from QH2 are passed to cytochrome c by complex 3
Complex 3
Q-cytochrome c oxidoreductase- its protein is ubiquinone-cytochrome c oxidoreductase. The flow of a pair of electrons through this complex leads to the effective net transport of 2H+ to the intermembrane space. This is half the yield obtained with NADH-Q reductase because of a smaller thermodynamic driving force. The Q cycle takes place here- it is a docking site for QH2 and cytochrome c, which electrons are transferred to. Electrons are transferred through an iron-sulfur cluster center. Contains binding sites for ubiquinone (QP and QN)
Cytochrome
An electron-transferring protein that contains a heme prosthetic group
Cytochromes of complex 3
Complex 3 contains 2 types of cytochromes (b and c1). The heme prosthetic group in cytochromes b, c1, and c is iron-protoporphyrin 9, the same heme present in myoglobin and hemoglobin. The iron ion of a cytochrome alternates between a reduced ferrous (+2) state and an oxidized ferric (+3) state during electron transport. The two cytochrome subunits of complex 3 contain a total of 3 hemes- there are 2 hemes within cytochrome b (heme bL- low affinity and heme bH- high affinity). There is also one heme within cytochrome c1. These identical hemes have different electron affinities because they are in different polypeptide environments.
2 hemes of cytochrome b
Heme bL (low affinity) is located in a cluster of helices near the intermembrane face of the membrane, and has a lower affinity for electrons. Heme bH has a higher electron affinity and is located near the matrix side
Structure of complex 3
The enzyme is a homodimer with each monomer consisting of 11 different polypeptide chains. The major prosthetic groups (3 hemes and a 2Fe-2S cluster) are located either near the edge of the complex bordering the intermembrane space or in the region embedded in the membrane. They are well positioned to mediate the electron transfer reactions between quinones in the membrane and cytochrome c in the intermembrane space
Heme A
Part of complex 4 of the electron transport system. Contains a hydrophobic tail
Heme B
Most common type of hemoglobin, present in hemoglobin and myoglobin
Heme C
Present in cytochrome c
proteins and links via cysteines
Complex 4
Cytochrome c oxidase- it catalyzes the transfer of electrons from the reduced form of cytochrome c to molecular oxygen, which is the final acceptor. Cytochrome c is oxidized, while oxygen is reduced to water. The requirement of oxygen for this reaction is what makes aerobic organisms aerobic
Complex 4 reaction
4 electrons are accepted total, one at a time. They are funneled to O2 to completely reduce it to water. Simultaneously, protons are pumped from the matrix into the intermembrane space. 2H+ are translocated across
the membrane. This reaction is thermodynamically favorable. Free energy from the reaction is captured in the form of a proton gradient for subsequent use in ATP synthesis.
Structure of complex 4
Consists of 13 subunits, 3 of which are encoded by the mitochondrial genome. Cytochrome c oxidase contains 2 heme A groups and 3 copper ions. There are arranged as two copper centers, designated A and B. One center, CuA/CuA,
contains two copper ions linked by two bridging cysteine residues. This center initially accepts electrons from reduced cytochrome c. The remaining copper ion, CuB, is bonded to three histidine residues,
one of which is modified by covalent linkage to a tyrosine residue. The centers alternate between the cuprous (reduced Cu+) and the cupric (oxidized Cu 2+) form as they accept and donate electrons
ATP synthase structural components (2)
- F1 – encodes the catalytic activity. Ball shaped, protrudes into the mitochondrial matrix
- F0 – acts as a proton channel crossing the inner mitochondrial
membrane. Stick shaped, embedded in the inner mitochondrial membrane
ATP synthase complex components (3)
- Rotor – 𝛾, 𝛿, and 𝜀 subunits
- Headpiece – catalytic piece – 𝛼3𝛽3 unit
- Stator – stabilizing arm (immobile)
F1 ATP synthase structure
Consists of 5 types of polypeptide chains- a3, b3, 𝛾, 𝛿, and 𝜀. The a and B subunits make up the bulk of F1 and are arranged alternately in a hexameric ring. Both bind nucleotides, but only the B subunits are catalytically active. Below these subunits, there is a central stalk consisting of the 𝛾 and 𝜀 proteins. The 𝛾 subunit breaks the symmetry of the a3B3 hexamer- each of the B subunits is differentiated by its interaction with a different face of 𝛾. Distinguishing the three B subunits is crucial for the mechanism of ATP synthesis
F0 ATP synthase
A hydrophobic segment that spans the inner mitochondrial membrane. F0 contains the proton channel of the complex. This channel consists of a ring comprising from 8 to 14 c subunits that are embedded in the membrane. The F0 and F1 subunits are connected in
two ways: by the central γ ɛ stalk and by an exterior column. The
exterior column consists of one a subunit, two b subunits, and the δ subunit.
Conformational changes in ATP synthase
Proteins flow through F0 component and the F1 subunit undergoes a conformational change from L (loose), T
(tight), and O (open). ADP and Pi bind to form ATP, and ATP is only released in the open position. The 𝛾 subunit rotates in 120 degree increments, in a counterclockwise direction as viewed from the matrix side. Each increment corresponds to the hydrolysis of a single ATP molecule. The enzyme appears to operate near 100% efficiency- essentially all of the energy released by ATP hydrolysis is converted into rotational motion. The dissipation of the proton gradient is what releases ATP.
Binding changes in ATP synthase
The O form of the subunit can bind or release nucleotides. The rotation of the γ subunit drives the interconversion of these
three forms (L, T, and O). ADP and Pi bound in the subunit in the T form are transiently combining to form ATP. If the γ subunit is rotated, the rotation converts the T-form site into an O-form site with the nucleotide bound as ATP. Simultaneously, the L-form site is converted into a T-form site, enabling the transformation of an
additional ADP and Pi into ATP. The ATP in the O-form site can now depart from the enzyme to be replaced by ADP and Pi. An additional120-degree rotation converts this O-form site into an L-form site, trapping these substrates. Each subunit progresses from the T to the O to the L form with no two subunits ever present in the same conformational form.
Experiment showing ATP synthase is a molecular motor
Beta subunits were attached to a surface, which is on the same side as the mitochondrial matrix. An actin filament is on the same side as the membrane. The γ subunit was linked to a fluorescently labeled actin filament to provide a long segment that could be observed under a fluorescence microscope. Remarkably, the addition of ATP caused the actin filament to rotate in a counterclockwise direction. The γ subunit was rotating, driven by the hydrolysis of ATP. Therefore, the catalytic activity of an individual molecule could be observed. The counterclockwise rotation is consistent with the predicted mechanism for hydrolysis
Why are transport systems in mitochondria necessary?
Biomolecules required for the electron transport system and
oxidative phosphorylation must be shuttled back and forth across the membrane. The inner mitochondrial membrane must be impermeable to most molecules, but exchange still has to take place between the cytoplasm and the mitochondria. The shuttles transfer 2e– from cytosolic NADH to carrier molecules
2 transport shuttles in mitochondria
- Malate–aspartate shuttle (liver)
- Glycerol-3-phosphate (muscle)
Glycerol 3-phosphate shuttle (3 steps)
- A pair of electrons from NADH can enter the ETC by being used to reduce dihydroxyacetone phosphate and form glycerol 3-phosphate
- Glycerol 3-phosphate is reoxidized by electron transfer to a FAD prosthetic group a membrane-bound glycerol 3-phosphate dehydrogenase.
- Subsequent electron transfer to Q to form QH2 allows these electrons to enter the ETC.
Glyceraldehyde 3-phosphate dehydrogenase
Catalyzes the reaction where electrons are transferred from NADH to dihydroxyacetone phosphate (an intermediate) to form glycerol 3-phosphate. Catalyzes the reaction when it occurs in the cytoplasm. The shuttle uses two isozymes of this enzyme
Importance of the glycerol 3-phosphate shuttle
The use of FAD enables electrons from cytoplasmic NADH to be transported into the mitochondria against an NADH concentration gradient. Electrons from NADH go into electron transport system through coenzyme Q. The price of this transport is one molecule of ATP per two electrons. This glycerol 3-phosphate shuttle is especially prominent in muscle and enables it to sustain a very high rate of oxidative phosphorylation
Malate-aspartate shuttle
Brings electrons from cytoplasmic NADH in the heart and liver. It is mediated by two membrane carriers and 4 enzymes. All reactions are reversible. This shuttle maintains the supply of NAD+
Malate-aspartate shuttle reaction (6 steps)
- Electrons are transferred from NADH in the cytoplasm to oxaloacetate, forming malate
- Malate traverses the inner mitochondrial membrane in exchange for alpha ketoglutarate
- Malate is then reoxidized by NAD+ in the matrix to form NADH in a reaction catalyzed by malate dehydrogenase
- The resulting oxaloacetate does not readily cross the inner mitochondrial membrane- a transamination reaction is needed to form aspartate. Aspartate can be transported to the cytoplasmic side in exchange for glutamate
- Glutamate donates an amino group to oxaloacetate, forming aspartate and alpha-ketoglutarate
- In the cytoplasm, aspartate is then deaminated to form oxaloacetate and the cycle is restarted
ATP-ADP translocase
Enables ATP and ADP to cross the permeability barrier of the inner mitochondrial membrane. The translocase acts as an antiporter. The flows of ATP and ADP are coupled- ADP enters the mitochondrial matrix only if ATP exits, and vice versa. It exports one ATP for every ADP imported
Why do ADP and ATP need assistance to cross the mitochondrial membrane?
ATP and ADP are unable to diffuse freely across the inner mitochondrial membrane. They are highly charged molecules that require a translocase protein to help them cross the membrane
Phosphate translocase
Translocates one Pi and one H+ into the matrix, due to the transport of one OH- out of the matrix. H2PO4 is exchanged for OH-. It works in concert with the ATP-ADP translocase. The translocase is similar to a channel and can be a symporter or an antiporter. Facilitates electrically neutral translocation
ATP synthasome
The ATP-ADP and phosphate translocase proteins work together to provide ATP synthase with its substrates. They are associated with the synthase to form a large complex called the ATP synthasome
Mechanism of ATP-ADP translocase (4 steps)
The translocase catalyzes the coupled entry of ADP into the matrix and the exit of ATP from it
1. The binding of ADP from the cytoplasm favors the turning inside out of the transporter
2. The transporter releases ADP into the matrix
3. Subsequent binding of ATP from the matrix to everted form favors eversion back to the original conformation
4. This causes ATP to be released into the cytoplasm
Regulation of oxidative phosphorylation
ADP and ATP control aerobic respiration. The ratio of NADH/NAD+ in the mitochondrial matrix controls
multiple steps in the citrate cycle.
The complete oxidation of glucose yields how many ATP?
About 30 molecules of ATP are formed when glucose is completely oxidized to carbon dioxide. 26 of the 30 molecules formed are generated by oxidative phosphorylation
Hereditary optic neuropathy
Cell death in optic nerve neurons causes subacute and lateral vision loss in teens/young adults. 90% of patients are male. Vision loss is usually permanent. It is a mitochondrial disease that is a result of mutations in complex 1
Respiratory control/acceptor control
The regulation of the rate of oxidative phosphorylation by the ADP level. Electron transport is tightly coupled to phosphorylation. Electrons don’t usually flow through the electron transport chain to oxygen unless ADP is simultaneously phosphorylated to ATP. When ADP concentration rises, like in active muscle, the rate of oxidative phosphorylation increases to meet the ATP needs of the muscle
How does the level of ADP affect the rate of the citric acid cycle?
At low concentrations of ADP, like in resting muscle, NADH and FADH2 are not consumed by the ETC. The citric acid cycle slows down because there is less NAD+ and FAD to feed the cycle. As the ADP level rises and oxidative phosphorylation speeds up, NADH and FADH2 are oxidized, and the citric acid cycle becomes more active. Electrons don’t flow from fuel molecules to oxygen unless ATP needs to be synthesized
Brown vs white adipose tissue
Differ in the size of lipid droplets inside the cell and the number
of mitochondria. Brown adipose tissue also has high levels of UCP1. Brown adipose tissue contains smaller fat droplets, which leave more space for mitochondria. In white adipose tissue, a large fat droplet fills the cytosolic space in each cell. The fat droplets are white, giving white adipose tissue its name
Mitochondrial diseases
Mutations in complex 1 are the most frequent cause of mitochondrial diseases. Some of these mutations impair NADH utilization, whereas others block electron transfer to Q. These diseases result in decreased ATP production. Most originate in neurons or in skeletal muscle cells.
Pellagra
A disease caused by low levels of niacin (vitamin B-3). It’s marked by dementia, diarrhea, and dermatitis
