Preface: In Part 1, the first four of seven subtopics were assayed for their occurrence in the literature. They were
1. Macromolecular (e.g. enzymes) transit through the GI tract; 2. The absorption and functioning of macromolecules from the GI tract; 3. The general molecular-structure of genes; and 4. How genes function, in the production and regulation of enzymes.
5) How enzyme function can be lost by the accumulation of excessive mutations:
As mentioned, the DNA needs to be unwound for transcription to proceed. The higher the level of transcription required, the more time the DNA spends in an unwound state. In an unwound state the double helix is subject to a greater degree of attack from environmental factors such as the presence of intercalating agents.
Intercalating agents are compounds such as Ethidium bromide (mentioned above) which insert between the strands of DNA and alter the degree of supercoiling. These agents can and do result in base pair mismatches during both DNA replication and RNA synthesis.  The mutations can occur during both processes. The subsequent mutations, as they build up over time, result in not only altered DNA sequences, but also altered gene products. For the case of this study, the gene products would be enzymes.
6) How external supplementation with enzymes can compensate for lost enzyme production capacity due to mutation burdens carried by the genes.
It is clear there are a multitude of ways in which enzyme level can be altered. These range from mutations in the DNA to RNA splicing errors to inactivation by another enzyme. The main culprit, as argued above, is the gradual, natural accumulation of DNA mutations over time. The external supplementation with enzymes relieves the problems associated with decreased enzyme levels in several ways.
First, external supplementation with enzymes directly adds back the enzymes, which were lost. The replacement enzymes can then function as though they were native to the system.
Second, external supplementation with enzymes earlier in the aging process allows for a down regulation of endogenous enzyme production. There is resulting decreased transcription from the enzyme genes, which lowers the chances of mutations to the actively transcribed genes. As seen above, the higher the level of transcription from a gene, the higher the chances for mutations in that gene.
7) The down regulation of transcription, by feedback inhibition due to external supplementation of enzymes, from genes coding for enzymes results in a lower mutation-rate in those genes. The decreased mutation rate allows for a more prolonged period of productive (i.e. functional) enzyme production. In addition, the down regulation of transcription by feedback inhibition serves to save tremendous energy over the lifetime of an organism [54-57]
Negative regulation by feedback inhibition is a well-established phenomenon.  In this process, a product of a pathway acts on that same pathway in a way, which diminishes the product's manufacture. The net effect of feedback inhibition is that a gene product decreases its own production.
Feedback inhibition (or end product inhibition) is a mechanism for the inhibition of enzyme...
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