Biology Question #995

Yossi Truzman, a 22 year old male from Ra`anana asks on October 27, 2002,

In our breathing system we have two coenzymes NADH and FADH2. Why do we have two coenzymes? And why is the NADH more efficient than FADH2, since FADH has two H+ connected to it, while NADH has one.

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The answer

Erika Plettner answered on November 4, 2002

We have both coenzymes (NADH and FADH2) not only in the breathing system (lungs and nasal epithelia), but in all tissues because the two cofactors serve different functions. NADH is a two-electron donor, while FADH2 can donate its two electrons one at a time or it can donate both simultaneously. Similarly, NAD+ accepts two electrons simultaneously (and one H+), while FAD can accept one electron to give a semiquinone, followed by another electron (and one H+) or FAD can also accept two electrons simultaneously. Some enzymes (such as dehydrogenases) require a two-electron redox partner (i. e. the NAD/NADH pair) while other enzymes require a partner capable of one-electron chemistry. In addition, reduced flavins such as FADH2 exhibit other very interesting and important chemistry, such as the reaction with dioxygen from air. FADH2 can form a hydroperoxide adduct, which in turn can do chemistry very similar to peracids commonly used in the laboratory for peroxidation and ester formation from ketones. For example, the enzyme that forms squalene epoxide from squalene (one important step towards the synthesis of cholesterol in our body) is a FADH2-containing enzyme. Finally, NADH is more reducing than FADH2, so often there is an electron-transfer chain, where two electrons from NADH (or its 3'-phosphorylated analog, NADPH) are used to reduce FAD to FADH2 and this, in turn, reduces a one-electron acceptor (such as Fe3+ in an iron-containing enzyme).

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