Goldfarb D. Biophysics DeMYSTiFied
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162 BiophysiCs D e mystifieD
two nucleotide strands are complementary. Two nucleotide strands are complemen-
tary if, in every place on one strand where there is an adenine, the other strand
contains thymine (or uracil) and vice versa. And in every place on one strand
where there is a guanine, the other strand contains cytosine (and vice versa).
Figure 7-21 shows hydrogen bonding between two strands of DNA.
Nucleic Acid Function
Nucleic acids serve a variety of functions in living things. Here we review only
the most major roles they play. We start with DNA, whose primary role is stor-
age, expression, and replication of genetic information.
We said that proteins are the worker bees of life; they play a major role in
pretty much all biological process. This includes everything from digestion, to
oxygen transport, to muscle contraction, sensory perception, eye color, hair
color, and the manufacture of biomolecules such as carbohydrates, lipids, nucleic
acids, and even proteins themselves, just to name some of the more major roles
proteins play. You also learned (in Chap. 2) that the specific shape and physical
Figure 7-20 • Hydrogen bonding between base pairs
in DNA.
Chapter 7 BiomoleCules 101 163
properties of a protein are intrinsically related to its function. Finally, you
learned a little earlier in this chapter that the specific shape and physical prop-
erties of a protein depend largely on two things: (1) its amino acid content
(which amino acids make up the protein) and (2) the specific order or sequence
of the amino acids in the polypeptide.
Given the major roles that proteins play, the enormous number of different
proteins, and the fundamental connection between a protein’s function and its
amino acid content and sequence, how does an organism know which amino acids
Figure 7-21 • Hydrogen bonding between two strands of DNA. (Adapted from Wikimedia Commons.)
164 BiophysiCs DemystifieD
to use for each different kind of protein and in what order to put those amino acids
together? This is where DNA comes in. The sequence of nucleotides in DNA is
actually a genetic code specifying the content and sequence of amino acids in each
protein. This is what is meant by storage of genetic information. Various sections of
the nucleotide sequence along a DNA polymer specify the amino acid sequence
for a particular protein. (Some sections of the nucleotide sequence, however, do
not appear to specify anything; possible reasons for this will be mentioned later, but
a complete discussion of these noncoding regions of DNA is more apt for an advanced
text.) Each such section of DNA that specifies the amino acids for a given protein
is called a gene. There is a concept in molecular biology of one gene, one protein.
The idea is that each gene contains the instructions for a particular protein, and
each different kind of protein is coded for by a particular gene.
In general one gene, one protein is true. But there is also a wide variety of excep-
tions to this rule. The actual situation is known to be quite complex. For example,
sometimes a gene codes for only a portion of a protein. And sometimes parts of an
amino acid sequence (although coded for by the gene) are removed by the organ-
ism before the polypeptide is finally assembled into a protein. Despite these com-
plexities, for our purpose of gaining a basic understanding the biophysics of these
molecules, the one gene, one protein rule will suffice. Figure 7-22 summarizes the
role of DNA as a storehouse of genetic information.
DNA nucleotide sequence
Amino acid sequence
Protein structure and function
Proteins involved in nearly all
biophysical processes
Figure 7-22 • DNA as a storehouse of genetic
information. Genetic information (physical
heredity) affects the entire organism through
proteins. In other words DNA contains the
blueprints for building proteins. Proteins, in
turn, are involved in all living functions,
including building all biomolecules. In this way,
DNA is effectively the blueprint for the entire
organism because it affects the entire organism
by specifying how to build each protein.
Chapter 7 BiomoleCules 101 165
One of the roles that DNA plays is expression of genetic information. By
expression we mean actually reading the instructions stored in DNA’s nucle-
otide sequence and starting the process of building a protein from them. To
explain how this happens, we first tell the short story, then tell it again but with
some details. Even so, what follows is just a basic description of gene expression;
we’ll leave the finer points for a text in molecular biology.
The short story is this: The DNA double helix unwinds to expose the nucle-
otide bases. A copy of the DNA nucleotide sequence is then made. This copy
is in the form of a single-stranded ribonucleic acid (RNA). The single-stranded
RNA molecule then moves to where protein synthesis will take place in the
cell. We call this type of RNA messenger RNA (mRNA) because, like a messen-
ger, it carries the blueprints from the DNA to the place where they are used to
build a protein. Next, a complex group of proteins and RNA molecules read
the nucleotide sequence in the mRNA and step by step link together the cor-
rect amino acids in the correct order (according to the instructions in the
mRNA) to make a protein.
That’s the short story; now a little more detail: When the DNA double helix
unwinds at the start of a gene (the beginning of a sequence that codes for a
particular protein), there are individual ribonucleotides floating around in solu-
tion. These ribonucleotides form hydrogen bonds with the deoxyribonucle-
otides on one of the exposed strands of the DNA. Keep in mind that hydrogen
bonding between nucleotide bases is pair specific. Then an enzyme called RNA
polymerase catalyzes the biochemical reaction to covalently link the ribonucle-
otides together. The result is the single-stranded mRNA molecule whose base
sequence is now complementary to the DNA sequence. Effectively the RNA
molecule is a copy or transcript of the base sequence in the gene. So the process
of synthesizing mRNA from DNA is called transcription. See Fig. 7-23.
When protein synthesis takes place, a number of enzymes and ribonucleic acids
get involved. One major player is a type of RNA called transfer RNA, (tRNA),
whose job it is to transfer each amino acid to the correct location in the growing
polypeptide chain. There are a number of different types of tRNA, one for each
amino acid. Each tRNA molecule has two specific binding sites. One part of the
tRNA molecule binds to a specific amino acid. The structure of this part of the
tRNA molecule and the structure of the amino acid are such that the tRNA
molecule binds specifically to that amino acid but not to others. The second bind-
ing site of the tRNA molecule has a specific nucleotide sequence, three nucle-
otides long, that can base-pair with the complementary sequence on the mRNA.
In this way the tRNA molecules translate the mRNA sequence into a sequence
of amino acids. Each three nucleotides in the mRNA are translated into a specific
166 BiophysiCs DemystifieD
amino acid. Figure 7-24 illustrates the process of translation, translating the
sequence of nucleotides in mRNA into a sequence of amino acids in a polypep-
tide chain.
Related to the idea of genetic expression is the concept of gene regulation, how
the organism decides when to express a particular gene versus when it’s time to
“turn the gene off” and stop building the particular protein. The organism uses a
wide variety of mechanisms for gene regulation. Without going into detail at this
time, it’s worth mentioning some general themes involved in gene regulation.
These include proteins binding to DNA (to encourage or discourage unwinding
of the double helix), various other molecules binding to the proteins involved in
gene expression, and conformational changes in proteins and/or DNA.
Now that we know where the sequence of amino acids in a protein comes
from, we could ask where the nucleotide sequence in DNA comes from. This
is where inheritance and DNA replication come in. One of the roles of DNA is
to replicate itself so that the nucleotide sequence can be passed on to the next
generation. The process of DNA replication has some similarities with transcrip-
tion. The double helix unwinds to expose the nucleotides, but now deoxyribo-
nucleotides in solution pair with the deoxyribonucleotides in the DNA strands.
The enzyme DNA polymerase then does the work of covalently connecting
together these nucleotides into a new DNA strand.
Figure 7-23 • Transcription of DNA to create an mRNA transcript, or copy, of the nucleotide sequence in a gene.
(Courtesy of National Human Genome Research Institute.)
Chapter 7 BiomoleCules 101 167
Amino acid
Growing
polypeptide
chain
3 nucleotide bases on tRNA base pair
with 3 nucleotide bases on mRNA
tRNA
mRNA
Figure 7-24 • Protein synthesis (building a protein from amino acids) involves
translation of an mRNA nucleotide sequence into an amino acid sequence by tRNA
molecules.
DNA replication, in contrast to transcription, uses both DNA strands as a
template to create a new nucleotide polymer. Figure 7-25 illustrates the process
of DNA replication. The newly formed DNA strands do not separate from the
original DNA. Instead, the replication results in two new DNA double helices,
where each new double helix is a combination of one strand from the original
DNA molecule and a newly synthesized complementary strand. Once the
DNA has been replicated, a copy of the DNA can be passed on to the next
generation through cellular division (one cell dividing into two).
Nucleotides as Energy Currency
One of the most important roles of nucleotides (outside of being the residues
that make up nucleic acids) is that of being energy currency for the cell. As we
mentioned, nucleotides sometimes contain two or even three phosphate groups
in a row. (See, e.g., Fig. 7-26.)
The covalent bonds between adjacent phosphate groups (pyrophosphate bonds)
contain a relatively large amount of energy. This energy is readily available by
breaking these bonds. Many enzymes couple simultaneous reactions that include
the breaking of a nucleotide pyrophosphate bond with a reaction that requires
energy. In this way the energy of the pyrophosphate bond is used to drive bio-
physical processes that would otherwise not be spontaneous. The nucleotide is
168 BiophysiCs DemystifieD
Figure 7-25 • DNA replication. Each new double helix consists of
one strand from the original DNA molecule, plus a newly synthesized
complementary strand. (Courtesy of Wikimedia Commons.)
Chapter 7 BiomoleCules 101 169
acting as energy currency, its only role in the process being to provide energy
where it is needed.
As an example, in the manufacture of proteins, attachment of an amino acid
to its tRNA requires converting one molecule of ATP (adenosine triphosphate)
to ADP (adenosine diphosophate). The energy released by breaking off the third
phosphate group (converting ATP to ADP) is used to form the chemical bond
between the amino acid and its tRNA. When the amino acid is then added to the
growing polypeptide chain, two GTP (guanosine triphosphate) molecules are
converted to GDP (guanosine diphosophate) to provide the energy needed to
form the peptide bond.
By far the most common nucleotide used as an energy currency is adenosine
triphosphate (ATP). We mentioned regarding lipids and carbohydrates that
among their roles is the role of storing energy. What’s the difference between
storing energy in lipids and carbohydrates versus the energy stored in the pyro-
phosphate bonds of ATP? The answer is that the energy in ATP is readily used in
many biophysical processes, whereas the energy in carbohydrates and lipids usu-
ally must first be put into pyrophosphate bonds before it can be used further to
drive biochemical reactions. You can think of the energy in carbohydrates and
lipids as money in the bank whereas ATP is like cash in your hand. When the
organism needs more energy, it breaks down the carbohydrates and lipids, using
the energy in these biomolecules to convert ADP back into ATP. The ATP then
can be used to drive other biophysical processes such as manufacture of proteins
and nucleic acids, pumping of ions across membranes, and so on.
(b)(a)
Figure 7-26 • Adenosine triphosphate (ATP) and adenosine diphosphate (ADP).
170 BiophysiCs DemystifieD
Quiz
Refer to the text in this chapter if necessary. Answers are in the back of the
book.
1. The process of converting the nucleotide sequence of an mRNA molecule into
an amino acid sequence in a polypeptide is called what?
A.
Transcription
B.
Translation
C. Transformation
D. Trans fat
2. Carbohydrates contain what three elements?
A.
Carbon, hydrogen, and rategen
B.
Nitrogen, oxygen, and carbon
C. Oxygen, carbon, and hydrogen
D. CHNOPS
3. A major role of lipids is what?
A.
Muscle contraction
B.
Phosphorylation of DNA
C. structure of phospholipids
D. structure of membranes
4. Carbon atoms usually form how many covalent bonds?
A. 2
B. 4
C. 6
D.
8
5. An amino acid is a molecule with what functional groups?
A. An amine and hydrochloric acid.
B. A hydroxyl and an amine.
C. A protein and a polypeptide.
D.
A carboxyl and an amine.
6. DNA and RNA are examples of
A. nucleic acids.
B. nucleotides.
C.
proteins.
D. lipids.
7. DNA is a
A. heteropolymer.
B. homopolymer.
Chapter 7 BiomoleCules 101 171
C. peptide polymer.
D. ribonucleotide polymer.
8. The helical shape of DNA is due primarily to
A. aromatic side chains.
B. base stacking.
C. hydrogen bonds.
D. van der Waals constant.
9. Proteins are involved in
A. DNA synthesis.
B. enzymatic processes.
C. lipid metabolism.
D.
all of the above
10. Which of the following is not true about proteins?
A. Proteins are polymers of amino acids.
B. polypeptide chains fold up into a specific shape necessary for the protein’s function.
C. Transfer RNAs carry amino acids to where they are needed for protein production.
D.
Peptide bonds hold base pairs together.