09.21 - COMPLEX I ✅.pdf

Structural Biology

A branch of molecular biology, biochemistry, and biophysics focused on the molecular structure of macromolecules and how their structures affect function.

Respiratory Chain

A series of reactions where complex metabolites are converted into monomeric units, oxidized to CO2, and reduced electron carriers are reoxidized to yield ATP.

Acetyl-CoA

A common intermediate in energy metabolism, formed from the transformation of monomeric units.

NAD+

An electron carrier that is reduced to NADH during the oxidation of substrates in cellular respiration.

FAD+

An electron carrier that is reduced to FADH2 during the oxidation of substrates in cellular respiration.

Oxidative Phosphorylation

The final stage of cellular respiration where reoxidation of NADH and FADH2 occurs by O2, yielding ATP and H2O.

Mitochondria

Organelles in eukaryotic cells where respiratory processes occur, particularly within the inner mitochondrial membrane.

Cristae

Invaginations of the inner mitochondrial membrane, increasing the surface area for oxidative phosphorylation.

Electrochemical Gradient

A gradient that comprises a chemical gradient (difference in concentration of protons) and an electrical gradient (differences in charge across a membrane).

Ubiquinone (Coenzyme Q)

An electron carrier in the electron transport chain, which accepts electrons from NADH and FADH2.

Cytochrome C

An electron carrier in the electron transport chain that transfers electrons between complexes.

Proton Pumping

The process of moving protons across the mitochondrial membrane to create an electrochemical gradient utilized for ATP synthesis.

ATP Synthase

An enzyme that uses proton flow down the electrochemical gradient to synthesize ATP from ADP and inorganic phosphate.

Complex I (NADH: Ubiquinone Oxidoreductase)

The first and largest complex in the electron transport chain, responsible for the oxidation of NADH and reduction of ubiquinone.

Hydrophilic Arm

The part of Complex I located in the mitochondrial matrix, containing subunits that interact with NADH.

Hydrophobic Arm

The part of Complex I embedded in the inner mitochondrial membrane, facilitating proton pumping.

Iron-Sulfur Clusters

Cofactors within the matrix arm of Complex I that transfer electrons one at a time.

Flavin Mononucleotide (FMN)

The first electron acceptor from NADH in Complex I, capable of carrying two electrons.

Quinone Binding Site

A cavity within Complex I where ubiquinone is reduced to ubiquinol.

Proton Translocation Activity

The action of pumping protons across a membrane, contributing to the electrochemical gradient.

Open Conformation

The inactive state of Complex I when NADH is not bound, allowing for a wider angle in the structure.

Closed Conformation

The active state of Complex I when NADH is bound, leading to a tighter structure.

State 1 of the Initial Hypothesis

The state where CoQ is not bound and CI is reduced with a loop in the Q cavity.

State 4 of the Initial Hypothesis

The state where quinol is quickly released into the lipid bilayer after electron transfer.

New Hypothesis of Electron and Proton Coupling

A proposed mechanism where protons exit from one main point rather than multiple, supported by structural changes and electrostatic interactions.

NDUFS2

A subunit in Complex I that contains the quinone binding site and undergoes conformational changes upon NADH binding.

NDUFV2

A subunit in Complex I involved in electron transfer and coordination of iron-sulfur clusters.

N1a

A structural subunit that provides antioxidant activity and is involved in reversing electron transfer when a cascade of electrons occurs.

NDUFS1

A subunit necessary for the coordination of electron transfer in Complex I.

NDUFS3

A structural subunit in Complex I not involved in catalysis but essential for maintaining overall structure.

ND1

A subunit in the membrane arm of Complex I that exhibits conformational changes based on NADH binding.

HL Helix

A long transmembrane helix in the ND5 subunit of Complex I, thought to be involved in stabilizing the complex.

Conformational Change

Structural adjustments within Complex I that occur during electron transfer and proton pumping.

Electrostatic Interactions

Forces between charged residues that contribute to signaling and coupling in the translocation of protons.

5 Iron-Sulfur Clusters

Cofactors typically found in Complex I that aid in the transfer of a single electron at a time.

Cryo-EM

A modern technique used in structural biology, allowing the study of macromolecules in multiple conformations.

Periplasm

The space between the inner and outer membranes of a bacterial cell where protons may be released during electron transport.

NADH Oxidation

The process where NADH donates electrons to Complex I, leading to its conversion back to NAD+.

Quinol

The reduced form of ubiquinone, produced in Complex I after accepting electrons.

Water Molecule Entrapment

A stage in the mechanism where water molecules interact with protons within the quinone binding site.

Supernumerary Subunits

Additional subunits in Complex I, concentrated at either side of the membrane domain, increasing size and complexity.