WELCOME TO DR. BILL'S INFORMATION SITE.                          LIVER FUNCTIONS

BIOTRANSFORMATION - is a concept where the original chemical form is changed into a new chemical form.

METABOLISM - is an older term that simply meant changing an active chemical form into an inactive form. However, we now know that some metabolic  changes result in the formation of active forms;  while others result in more toxic active forms. To cover this spectrum, it is best to use the term biotransformation rather than metabolism.

Chemicals can typically be classified as, either: - water soluble or - lipid soluble. If they are water soluble it is possible to excrete them through the kidneys. However, if they are lipid soluble - then kidney excretion is not feasible. The liver has the prime responsibility of altering chemical structure to allow excretion. Typically,  chemical altering activities in the liver occur in the cytochrome P450 system. There are two phases in biotransformation which can be identified.

The two phases are simply referred to as: phase I reactions and phase II reactions. In phase I reactions (referred to as nonsynthetic reaction),  the original chemical is modified to make it more water soluble - if it was water soluble to begin with - OR  - to make it water soluble - if it was originally lipid soluble. In phase II reactions, the modified chemical is usually combined with either: glucuronic acid, sulfate, acetyl or glutathione. This combination of chemical plus new group (referred to as synthetic reaction) allows the kidney to more readily excrete the complex. Some chemicals will undergo: phase I only phase II only phase I followed by phase II multiple metabolites are possible.

Examples of the above include: excretion of diazepam  (Valium) involves both phase I and phase II reactions excretion of lorazepam (Ativan) involves phase II only. Interestingly, both are benzodiazepines but are handled differently by the liver. excretion of cimetidine (Tagamet)(an antiulcer drug) involves only phase I (no phase II).

The importance of having properly functioning liver and kidneys cannot be overemphasized. To illustrate this point, let's consider the drug meperidine (Demerol). Meperidine is an effective analgesic (pain reliever) but it has a short duration of action in the body because the liver changes it  (by phase I reaction ) to normeperidine. Normeperidine has little if any analgesic action but can cause seisures if it builds up in the body. When would it accumulate? If the kidneys are not functioning properly, normeperidine starts building up. Keeping in mind that meperidine is being administered every 2 to 3 hours (to provide analgesic action), and keeping in mind that if the liver is functional - then the seisure side effect of normeperidine is enhanced.

liver anatomy and more