Cell Metabolism - Bioprocess Engineering: Kinetics, Biosystems, Sustainability and Reactor Design - page 476

this information is translated into proteins. The proteins then perform a structural or enzymatic
role, mediating almost all the metabolic functions in the cell. The information content of the
DNAmolecule is static; changes occur very slowly through infrequent mutations or rearrange-
ments nearly by accidents. Which species of RNA that are present and in what amount varies
with time and with changes in culture conditions. Likewise, the proteins that are present will
change with time but on a different timescale than for RNA species. Some of the proteins
produced in the cell bind to DNA and regulate the transcriptional process to form RNAs.
The important feature of the central dogma is its universality from the simplest to most
complex organisms. One important, although relatively minor, deviation is that some RNA
tumor viruses (retroviruses) contain an enzyme called reverse transcriptase. The virus that
causes AIDS, the human immunodeficiency virus or HIV, is a retrovirus (one approach to
treatment is to selectively inhibit reverse transcriptase). In this case, the virus encodes infor-
mation on an RNA molecule. In the host cell, viral reverse transcriptase produces a viral
DNA molecule using the viral RNA as a template. Such viruses are clinically important
and the enzyme, reverse transcriptase, is an important tool in genetic engineering. Nonethe-
less, the process depicted in Fig. 10.1 is essentially applicable to any cell of importance.
In the case of HIV, reverse transcriptase is responsible for synthesizing a complementary
DNA (cDNA) strand to the viral RNA genome. An associated enzyme, ribonuclease H, digests
the RNA strand, and reverse transcriptase synthesizes a complementary strand of DNA to form
a double-helix DNA structure. This cDNA is integrated into the host cell's genome via another
enzyme (integrase) causing the host cell to generate viral proteins that reassemble into newviral
particles. Subsequently, the host cell undergoes programmed cell death, apoptosis.
Some eukaryotic cells contain an enzyme with reverse transcription activity called telome-
rase. Telomerase is a reverse transcriptase that lengthens the ends of linear chromosomes.
Telomerase carries an RNA template from which it synthesizes DNA repeating sequence,
or “nonsense” DNA. This repeated sequence of DNA is important because every time a linear
chromosome is duplicated it is shortened in length. With “nonsense” DNA at the ends of
chromosomes, the shortening eliminates some of the nonessential, repeated sequence rather
than the protein-encoding DNA sequence farther away from the chromosome end. Telome-
rase is often activated in cancer cells to enable cancer cells to duplicate their genomes indef-
initely without losing important protein-coding DNA sequence. Activation of telomerase
could be part of the process that allows cancer cells to become technically immortal.
For information storage and exchange to take place, there must be a “language.” As shown
in Table 2.5, there are 20 or 21 amino acids of general structure that make up the building blocks
for all the organisms. We need a minimum of 20 or 21 “words” for the language to be useful.
FromFig. 2.30, one can observe that there are four letters that can be assigned to all the building
blocks of DNA (A, T, G, C) and/or RNA (A, U, G, C). Therefore, we can conceive of all life as
using a four-letter alphabet made up of the nucleotides discussed in Chapter 2 (that is, A, T, G,
andC inDNA). To have the language capable of expressing 20 or 21 individual words, we need
to use three letter combinations from the four letters. All words are three letters long; such
words are called codons. With four letters and only three-letter words, we have a maximum
of 64 words, which is more than 20. There are then multiple expressions (words) to describe
one particular “meaning.” These words, when expressed, represent a particular amino acid
or “stop” (when it does not represent a particular amino acid) protein synthesis. This natural
“language” design is essential to DNA, RNA, and proteins.