NADH dehydrogenase
Summary
NADH dehydrogenase (Complex I) is the first and largest enzyme complex of the electron transport chain, catalyzing the transfer of electrons from NADH to coenzyme Q while pumping protons across the inner mitochondrial membrane. Deficiencies cause mitochondrial myopathies and neurological disorders due to impaired ATP synthesis.
Detail
NADH dehydrogenase (NADH:ubiquinone oxidoreductase, Complex I) is a massive L-shaped enzyme complex embedded in the inner mitochondrial membrane, consisting of 45 subunits in mammals. It catalyzes the oxidation of NADH to NAD+ while reducing coenzyme Q (ubiquinone) to ubiquinol, transferring two electrons through a series of iron-sulfur clusters and flavin cofactors. This process is coupled to the pumping of 4 protons from the mitochondrial matrix to the intermembrane space, contributing to the proton-motive force essential for ATP synthesis. Complex I is the entry point for electrons from glycolysis, fatty acid oxidation, and the citric acid cycle. Dysfunction leads to decreased ATP production and increased reactive oxygen species (ROS) generation. Clinical manifestations of Complex I deficiency include Leber hereditary optic neuropathy (LHON), mitochondrial encephalomyopathy, exercise intolerance, and neurodegeneration. It's inhibited by rotenone and piericidin A, which are used as research tools and pesticides.
Sources
- Lehninger Principles of Biochemistry
- Harper's Illustrated Biochemistry
- First Aid for the USMLE Step 1
- Robbins Basic Pathology
- Nature Reviews Molecular Cell Biology
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