Almost all tissues contain an oxidative system, separate from the electron transport system, that is used for a number of important reactions. This system is usually part of the endoplasmic reticulum, although there is also a mitochondrial version. Experimentally, the ER system is isolated in the microsomal fraction of cell centrifugation and it is also known as the microsomal oxidizing system. These systems contain a number of different cytochromes known collectively as the cytochrome P450 system (historically, they were first identified by a strong absorption in the visible range at 450 nm). The reaction catalyzed by this system involves oxidations, usually from carbon atoms to the alcohol level. A number of different kinds of oxidations are catalyzed however and the term mixed-function oxygenase is frequently used. The oxidizing agent is molecular oxygen but only one atom of oxygen is used so this is frequently also referred t o as a monooxygenase. The other oxygen is reduced by NADPH:

substrate + NADPH + 02 --------> NADP+ + substrate -(OH) + H2O

The terms microsomal oxidizing system, cytochrome P450, monooxygenase, and mixed-function oxygenase are used more or less interchangeably.

The P450 system is important in a number of different physiologic prodesses:

• Steroid metabolism, being associated with most of the enzymes involved in the production of steroid hormones, including the complicated first step of conversion of cholesterol to pregnenolone.
• Detoxification system and many foreign substances that are highly hydrophobic become hydroxylated to the point that they are more soluble and can be acted upon by enzymes that will destroy them.
• Heme degradation is mediated by P450 oxidations. The process involves the two step oxidation of heme to biliverdin and bilirubin. As Stryer points out, you can follow these reactions by watching color changes in a bruise. Click here for an external site (NetBiochem) with information on heme degradation.
• The P450 system is also involved in the processing of ethanol, especially when there is a high dietary intake (greater than 10-20 % of calories). Because it is less efficient than the normal mitochondrial system (as a food source gives roughly 5 instead of 7 kilocalories), and because it will intefere with the processes described above, the activation of this system for alcohol oxidation, is considered one of the deleterious effects of alcoholism.