Explain how mutagens can cause genetic mutations in spite of your bodys DNA repair enzymes?

Answer 1

Primarily: "a lethal illness can be caused by the malfunction of just one type of enzyme out of the thousands of types present in our bodies."

A. Mutagens can over power the enzymes like cancer does with wild growth.
B. Mutagens infect a mutation that the body and its enzymes don't react to, it may be too subtle.
C. The enzymes themselves can cause genetic diseases if they are found in concentrations that are too high or too low.
D. The enzymes can be affected by temperature or other activities, like the pH value and the chemicals around it. In case of anemia or when the pH value is slightly off or under other circumstances the enzyme can be inhibited from acting.
E. Chemicals called inhibitors exist that can slow down or stop the action of enzymes, many of these are poisons.
F. The enzymes themselves can malfunction by a genetic mutation. This is just one way that cancer can attack the body.

According to Wikipedia: http://en.wikipedia.org/wiki/Enzymes
"Enzyme activity can be affected by other molecules. Inhibitors are molecules that decrease enzyme activity; activators are molecules that increase activity. Many drugs and poisons are enzyme inhibitors. Activity is also affected by temperature, chemical environment (e.g. pH), and the concentration of substrate. Some enzymes are used commercially, for example, in the synthesis of antibiotics. In addition, some household products use enzymes to speed up biochemical reactions (e.g., enzymes in biological washing powders break down protein or fat stains on clothes; enzymes in meat tenderizers break down proteins, making the meat easier to chew).

Since the tight control of enzyme activity is essential for homeostasis, any malfunction (mutation, overproduction, underproduction or deletion) of a single critical enzyme can lead to a genetic disease. The importance of enzymes is shown by the fact that.

One example is the most common type of phenylketonuria. A mutation of a single amino acid in the enzyme phenylalanine hydroxylase, which catalyzes the first step in the degradation of phenylalanine, results in build-up of phenylalanine and related products. This can lead to mental retardation if the disease is untreated.

Another example is when germline mutations in genes coding for DNA repair enzymes cause hereditary cancer syndromes such as xeroderma pigmentosum. Defects in these enzymes cause cancer since the body is less able to repair mutations in the genome. This causes a slow accumulation of mutations and results in the development of many types of cancer in the sufferer."

According to Wikipedia: http://en.wikipedia.org/wiki/Enzyme_inhibitor
"Enzyme inhibitors are molecules that bind to enzymes and decrease their activity. Since blocking an enzyme's activity can kill a pathogen or correct a metabolic imbalance, many drugs are enzyme inhibitors. They are also used as herbicides and pesticides. Not all molecules that bind to enzymes are inhibitors; enzyme activators bind to enzymes and increase their enzymatic activity."

Answer 2

Many times the normal DNA repair enzymes are the ones that introduce mutations. Different pathways such as nucleotide excision, mismatch repair actions directly result in nucleotide changes otherwise, mutations would only be because of a faulty enzyme and that is not true. Example: Somatic hypermutation (SHM) is a process that introduces point mutations in immunoglobulin receptor genes (part of a process known as affinity maturation) simply so antibodies can bind antigens better. In SHM an enzyme cytidine deaminase removes amino group from cytosine (deamination) which obviously makes the cytosine an uracil. Now, DNA repair systems identify this mismatch and another enzyme - uracil DNA glycosylase removes the uracil in attempt to repair this mismatch. I am not very clear on the mechanism downstream but creation of abasic site and so on results in nucleotide change in most cases. You might as well live in a bubble if you have a defective cytidine deaminase. Some of those bubble boy cases are related to this defect or equivalent genes.
Relation to mutagens: The enzymes repair DNA in similar manner whether the cause was endogenous or from environment. If cytosine deamination above was from a mutagen such as nitrous acid, then you might end up with a mutation as well. The point I am trying to make is that the enzyme doesn't have to be defective.

Answer 3

There are many possibilities. There could be a problem with the Repair enzyme it self which will allow all or some genetic problems to be ignored. Or there are some 'neutral mutations' that are ignored by the repair system and they can accumulate to a genetic drift.