Metabolism/Energy Overview Glycolysis Citric Acid Cycle  Elmhurst College
Cell Structure Energy Storage - ATP FAD, CoQ, CoA  Chemistry Department
Energy Overview NAD+ Electron Transport  Virtual ChemBook


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NAD+ - Nicotinamide Adenine Dinucleotide

Introduction:

NAD - Nicotinamide Adenine Dinucleotide is nonprotein component of certain enzymes and is called the cofactor. If the cofactor is organic, then it is called a coenzyme. Coenzymes are relatively small molecules compared to the protein part of the enzyme. Many of the coenzymes are derived from vitamins.

The coenzymes make up a part of the active site, since without the coenzyme, the enzyme will not function.

In the graphic on the left is the structure for the coenzyme, NAD+, Nicotinamide Adenine Dinucleotide. Nicotinamide is from the niacin vitamin. The NAD+ coenzyme is involved with many types of oxidation reactions where alcohols are converted to ketones or aldehydes. It is also involved in the first enzyme complex 1 of the electron transport chain.

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Role of NAD+:

One role of NAD+ is to initiate the electron transport chain by the reaction with an organic metabolite (intermediate in metabolic reactions) . This is an oxidation reaction where 2 hydrogen atoms (or 2 hydrogen ions and 2 electrons) are removed from the organic metabolite. (The organic metabolites are usually from the citric acid cycle and the oxidation of fatty acids--details in following pages.) The reaction can be represented simply where M = any metabolite.

MH2 + NAD+ -----> NADH + H+ + M: + energy

One hydrogen is removed with 2 electrons as a hydride ion (H-) while the other is removed as the positive ion (H+). Usually the metabolite is some type of alcohol which is oxidized to a ketone.


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Alcohol Dehydrogenase

Active Site:

The NAD+ is represented as cyan in the graphic on the left. The alcohol is represented by the space filling red, gray, and white atoms.

The reaction is to convert the alcohol, ethanol, into ethanal, an aldehyde.

Reaction: CH3CH2OH + NAD+ ---> CH3CH=O + NADH + H+

This is an oxidation reaction and results in the removal of two hydrogen ions and two electrons which are added to the NAD+, converting it to NADH and H+. This is the first reaction in the metabolism of alcohol.

The active site of ADH has two binding regions. The coenzyme binding site, where NAD+ binds, and the substrate binding site, where the alcohol binds. Most of the binding site for the NAD+ is hydrophobic as represented in green.

Three key amino acids involved in the catalytic oxidation of alcohols to aldehydes and ketones. They are ser-48, phe 140, and phe 93.

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