What is NAD/NADH anyway?

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Nicotinamide Adenine Dinucleotide (NAD) is a dinucleotide that functions as one of the most important coenzymes in the cell.

The interconversion of NAD between the reduced (NADH) and oxidized (NAD+) forms is a common reaction in biological redox (oxidation-reduction) reactions. In cells, most oxidations are accomplished by the removal of hydrogen atoms. Each molecule of NAD⁺ can acquire two electrons; that is, be reduced by two electrons. However, only one proton accompanies the reduction. The other proton produced as two hydrogen atoms are removed from the molecule being oxidized is liberated into the surrounding medium. For NAD, the reaction is thus:

NAD⁺ + 2H -> NADH + H⁺

NAD participates in many redox reactions in cells, including:

The bottom line on glycolysis is that glucose is oxidized to 2 moles of pyruvic acid. The oxidizing agent is NAD+, which is reduced to NADH. The process is exergonic and the mechanism that has evolved allows the energy of reaction to be captured as two moles of ATP per glucose molecule:

2 NAD⁺ + glucose + 2 ADP ------> 2 pyruvate + 2 NADH + 2 ATP

For most tissues in higher organisms, the pyruvate is further oxidized all the way to CO₂ (in the citric acid cycle ). Here, too, the major oxidizing agent is NAD+, although other oxidizing agents are also needed. The citric acid cycle pathway consists of eight reactions that process incoming molecules of Acetyl-CoA. The carbon atoms leave the cycle in the form of molecules of carbon dioxide. The hydrogen atoms and electrons leave the cycle in the form of reduced coenzymes NADH and FADH2. The cycle is regulated by three allosteric enzymes in response to cellular levels of ATP. One Acetyl CoA molecule entering the citric acid cycle produces three molecules of NADH, one of FADH2, and one of GTP. Click here to see the citric acid cycle.

Nicotinamide adenine dinucleotide, NADH, plays a central role in oxidative metabolism . Through the mitochondrial electron transport chain and a series of intermediate redox reactions, NADH can transfer two electrons and a hydrogen ion to molecular oxygen, liberating 52.6 kcal/mole. This is enough energy to synthesize 7.2 ATPs from ADP and Pi. Some inefficiency, though, allows only 3 ATPs to be formed.

For those organisms or tissues that do not carry out aerobic (oxygen-dependent) metabolism, there is the problem of re-generating the oxidizing agent NAD+. For mammalian tissues such as muscle and red blood cells, and for some microorganisms such as lactic acid bacteria, the NADH is used to reduce pyruvate to lactate.

pyruvate + NADH ----> lactate + NAD⁺

For other microorganisms the pyruvate can be further oxidized to acetaldehyde which can then be reduced by NADH to a number of different products depending on the particular organism. Ethanol-producing yeast and bacteria, reduce acetaldehyde:

1. Pyruvate decarboxylase (thiamine pyrophosphate enzyme similar to pyruvate dehydrogenase):

pyruvate ----> acetaldehyde + CO₂

2. Alcohol dehydrogenase: acetaldehyde + NADH ----> ethanol + NAD⁺

For mammals, the acetaldehyde, which is very toxic, must be further oxidized to acetic acid.

Why is NAD+ a Hydrogen Acceptor?

NADH: Natures Most Powerful Energizer

Oxidation Reactions and Enzymes

Chemical Structure of Biologically Important Compounds

TCA Cycle, Respiration, and Oxidative Phosphorylation