What is metabolism?
Metabolism is defined in the Shorter Oxford English Dictionary as “The sum of the chemical processes in a cell or organism, by which complex substances are synthesised and broken down, and growth and energy production sustained”. Every living cell, whether an individual single cell such as a bacterium or a cell that is part of large organisms such as a human being, has a metabolism. Countless thousands of interconnected chemical reactions result in the break down of products and the generation of new products in order to let the body or the cell function.
Does metabolism differ from organism to organism?
Yes, and luckily many viruses, bacteria and parasites have parts of their metabolism that differ from the metabolism of the human body. These differences have been, and are being, exploited to develop effective and accurate drugs.
Why is metabolism important in the development of new medicines?
Metabolism generates all the products needed by a cell or a body to be able to live. The drugs that we take in order to fight or prevent disease interact with the metabolism of cells or the body in order to stop or alter processes that are not desired. This might for example lead to the death of viruses, bacteria or parasites that have infected the body, or to the prevention of unwanted (auto-)immune responses in the case of autoimmune diseases or transplantation. The drugs are also often changed by the metabolism of the body, and this is often a deliberate part of the design of the drug.
Ideally drugs should only interfere with the metabolic process or processes in a cell or a body that are not wanted. For example a good antibiotic kills only bacteria and not the cells of the human taking the antibiotic. However it is usually not a simple question of yes or no, but more a question of degree. Often at one concentration a drug will be safe, and work as hoped, but at a higher concentration it may be lethal to humans. To be able to develop safe and effective drugs, to ensure that they work only against the desired metabolic processes, and to determine safe dosages it is vital that we understand the metabolism(s) involved.
How do we test whether new drugs are safe and effective?
Firstly we test whether they work on cells in culture. If they are effective in culture, new drugs can then be tested in small animals, such as mice and rats. However, there are very significant differences between the metabolisms of different animals. Although these differences may sometimes appear to be small, they can have an enormous impact on the effectiveness and safety of drugs. The same drug can often be inactivated much more rapidly by the metabolism of one animal when compared with another. To give one example, mice have much higher levels of a certain enzyme (called an esterase) in their blood than do monkeys and humans. Importantly, this enzyme degrades a number of drugs rapidly. When such a drug is tested in mice whose activity is interfered with by this enzyme, the outcome is quite different from that seen in humans. In contrast, there is a very close similarity between the metabolism of humans and monkeys. This means that experiments in monkeys can often play a vital role in evaluating new drugs.
As well as basic differences in metabolism, the pattern of disease that, for example, a mouse or a rat gets is quite different from that seen in humans. Where it is important to measure the effectiveness of a new drug against a disease, this often means that the drug must be tested in animals that respond much more like humans. Thus, in order to measure the effectiveness of a drug against a disease, experiments in monkeys can often be necessary.