Biological Oxidations and NAD.

Living organisms obtain energy by carrying out oxidation-reduction reactions. For animals this means burning food. The two major processes are glycolysis and the TCA cycle.

Glycolysis. The bottom line on glycolysis -- the point of all the complicated steps that you have studied in Biochemistry -- is that glucose is oxidized to 2 moles of pyruvic acid. The oxidizing agent is NAD+ which is, in turn reduced to NADH. NAD+ is a good oxidizing agent for this reaction and the process is exergonic and the mechanism which 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

Aerobic and anaerobic metabolism. For most tissues in higher organisms, the pyruvate is further oxidized all the way to CO2 (in the tricarboxylic acid cycle). Here, too, the major oxidizing agent is NAD+ although other oxidizing agents are also needed. The NADH and other reduced coenzymes that result from these oxidations are ultimately re-oxidized by molecular oxygen (through intermediate redox reactions in the electron transport chain). For this reason, this is referred to as aerobic metabolism. Because these processes depend on complex organelles (mitochondria) not every type of cell or organism can carry out aerobic respiration and must use the ATP obtained from glycolysis for energy.

Paths of anaerobic metabolism. For those organisms or tissues that do not carry out aerobic metabolism, there is the problem of re-generating the oxidizing agent NAD+. For mammalian tissues such as muscle and RBC, 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+

The second enzyme, is the same kind of enzyme that metabolizes the ethanol in mammalian liver (in the reverse direction, of course). For mammals, the acetaldehyde, which is very toxic, must be further oxidized to acetic acid.

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