Physiology of Protein

Introduction
Proteins are biopolymeric structures composed of amino acids, of which there are 20
commonly found in biological chemistry. Proteins serve as structural support, biochemical
catalysts, hormones, enzymes, building blocks, and initiators of cellular death. Proteins can
be further defined by their four structural levels: primary, secondary, tertiary, and quaternary.
The first level is the primary structure because it is the most basic level of protein structure.
It is composed of the linear order of amino acid residues. All of the residues connect via
peptide bonds. These linkages have designated carbon atom positions of alpha, beta, and
gamma, which correspond to specific positions relative to the peptide linkage. This structure
also has the name of the protein backbone.
The second level of protein structure is the secondary structure, and it consists of the various
shapes formed via hydrogen bonding. These shapes include alpha helix, beta-pleated sheet,
and beta-turn. As previously stated, hydrogen bonds stabilize all of these shapes.
The third level of protein structure is the tertiary structure. It consists of the three-
dimensional shape that will form when the polypeptide chain "backbone" interacts with an
aqueous environment, which immediately begins to form when a newly synthesized
polypeptide chain exits the terminal end of the ribosomal subunit complex. The polypeptide
chain sequesters hydrophobic residues and exposes those that are hydrophilic; this is all to
achieve thermodynamic stability. This thermodynamic stability is further driven by a variety
of chemical interactions including hydrogen bonds, Vanderwall forces, and ionic bonding
(the term ionic bonding includes electrostatic interactions and salt bridges). The energy that
these interactions can produce ranges from 0.1 to 3 kilocalories per mole. The fourth and
final level of protein structure is called the quarternary structure. This level is when
complexes form from multiple polypeptide chains called subunits. An example of this is
hemoglobin and how its tetrameric structure forms when two alpha and two beta subunits are
held together by chemical interactions. Therefore, it is appropriate to say that quaternary
structure is the three-dimensional arrangement of two or more polypeptides in a protein, each
of which folds independently of the other. It is important to note that the term subunit is
interchangeable with protomer. An example of clinical significance is in sickle cell anemia,
whereby the hemoglobin protein possesses amino acids that are insoluble in an aqueous
environment, driving the defective hemoglobin to aggregate to hide newly formed
hydrophobic residues and achieve thermodynamic favorability. These altered hemoglobin
molecules then form polymers that manifest as long, inflexible rods. These macromolecules
continue to elongate until they eventually precipitate and distort the red blood cell plasma
membrane into the classic sickle shape seen in a sickle cell crisis.
Nucleic Acids to Amino Acids: DNA Specifies Protein
Once it was determined that messenger RNA (mRNA) serves as a copy of
chromosomal DNA and specifies the sequence of amino acids in proteins, the question of
how this process is carried out naturally followed. It had long been known that only 20 amino
acids occur in naturally derived proteins. It was also known that there are only four
nucleotides in mRNA: adenine (A), uracil (U), guanine (G), and cytosine (C). Thus, 20 amino
acids are coded by only four unique bases in mRNA, but just how is this coding achieved?
The Codon
The discordance between the number of nucleic acid bases and the number of amino acids
immediately eliminates the possibility of a code of one base per amino acid. Even two
nucleotides per amino acid (a doublet code) could not account for 20 amino acids (with four
bases and a doublet code, there would only be 16 possible combinations [42 = 16]). Thus, the
smallest combination of four bases that could encode all 20 amino acids would be a triplet
code. However, a triplet code produces 64 (43 = 64) possible combinations, or codons. Thus,
a triplet code introduces the problem of there being more than three times the number of
codons than amino acids. Either these "extra" codons produce redundancy, with multiple
codons encoding the same amino acid, or there must instead be numerous dead-end codons
that are not linked to any amino acid.
Preliminary evidence indicating that the genetic code was indeed a triplet code came from an
experiment by Francis Crick and Sydney Brenner (1961). This experiment examined the
effect of frameshift mutations on protein synthesis. Frameshift mutations are much more
disruptive to the genetic code than simple base substitutions, because they involve a
base insertion or deletion, thus changing the number of bases and their positions in a gene.
For example, the mutagen proflavine causes frameshift mutations by inserting itself between
DNA bases. The presence of proflavine in a DNA molecule thus interferes with the
molecule's replication such that the resultant DNA copy has a base inserted or deleted.
Crick and Brenner showed that proflavine-mutated bacteriophages (viruses that
infect bacteria) with single-base insertion or deletion mutations did not produce functional
copies of the protein encoded by the mutated gene. The production of defective proteins
under these circumstances can be attributed to misdirected translation. Mutant proteins with
two- or four-nucleotide insertions or deletions were also nonfunctional. However, some
mutant strains became functional again when they accumulated a total of three extra
nucleotides or when they were missing three nucleotides. This rescue effect provided
compelling evidence that the genetic code for one amino acid is indeed a three-base, or
triplet, code.
Degeneracy of the Amino Acid Code
Examination of the full table of codons enables one to immediately determine whether the
"extra" codons are associated with redundancy or dead-end codes (Figure 1). Note that both
possibilities occur in the code. There are only a few instances in which one codon codes for
one amino acid, such as the codon for tryptophan. Note also that the codon for the amino acid
methionine (AUG) acts as the start signal for protein synthesis in an mRNA. Moreover, the
genetic code also includes stop codons, which do not code for any amino acid. The stop
codons serve as termination signals for translation. When a ribosome reaches a stop codon,
translation stops, and the polypeptide is released.
 Figure 1. DNA Codons and Amino Acids

Cellular Level
Transportation
Proteins, produced on ribosomes in the rough endoplasmic reticulum, are transferred to the
smooth endoplasmic reticulum to be processed into vesicles for intracellular transport.
Proteins are also responsible for targeting the vesicles through a series of interactions, which
include receptor and substrate interactions. The Golgi apparatus is made up of the cis, medial,
trans, and trans-Golgi network. James Rothman proposed in the 1980s that proteins processed
by the Golgi apparatus are transported from one sac to the next in vesicles. This concept is
important because it was not well understood how proteins could stay and act as Golgi-
specific enzymes, especially since virtually all Golgi enzymes are membrane proteins. This
proposal led to three different theorized pathways by which proteins are processed and
transported.
The three pathways are:
 Secretory
 Lysosomal
 Regulated
Secretory Transport
Constitutive secretion is a continuous pathway that takes place in all cells. It is thought to be
how cells produce new plasma membranes. It's also how exocytosis occurs. Vesicles in the
cytosol fuse with the plasma membrane. Fluid membranes facilitate membrane fusion
because of the principle that "like dissolves like." This theory asserts that a signal and a
complement receptor (which is on the Golgi) are necessary for sorting in the Golgi. This
theory derives from the well-established concept that a signal and its complement receptor
are fundamental components of all intracellular vesicular sorting.
Lysosomal Transport
Defined as the constitutive lysosomal pathway, this theory asserts that transport vesicles
containing lysosomal enzymes form a lysosome when intracellular vesicles fuse vesicles
formed from the plasma membrane during endocytosis. The lysosome is the site within a cell
where macromolecules degrade into their respective monomers. (e.g., proteins,
polysaccharides, polynucleotides, and lipids. These are the basic building blocks: amino
acids, monosaccharides, and nucleotides. There is no single building block for lipids, but
fatty acids come closest. The cell reuses building blocks to make new macromolecules.
Regulated Transport
This regulated secretory pathway only takes place in cells specialized for secretion. (e.g., B
lymphocytes secrete antibodies). Vesicles containing specialized proteins for secretion bud
off of the trans-Golgi network region of the Golgi apparatus. The secretory vesicle then
remains in the cytosol. The ligand binds to a ligand-binding site on the extracellular matrix
facing transmembrane receptor protein. After binding to a ligand (e.g., neurotransmitter or
hormone), this causes the receptor to undergo a conformational change, thus activating the
signal transduction pathway. The signal transduction pathway could cause an increase in
intracellular calcium levels. The extracellular concentration of calcium is 1x10(^-3).
Intracellular calcium concentration is 1x10(^-7). Calcium influx activates the cell once
intracellular concentration reaches 5x10^ (-6) M. The cytosolic secretory vesicles then move
to the plasma membrane for exocytosis.
Peptide Bonds
Peptide bonds form when the carboxyl group of the amino acid on the left attacks the amino
group of the amino acid on the right. The amino terminal is always to the left. The carboxy-
terminal is always to the right. The polarity of each amino acid is due to its R-group. A
peptide bond has three features: plantar, restricted mobility, and trans configuration.
Restriction enzymes are often utilized in laboratory procedures to sequence specific proteins.
The history of protein sequencing is beyond the scope of this article.
Disulfide Bonds
These are also known as disulfide bridges; these bonds form by nearby cysteine residues
within the protein. The cysteine residue has a non-polar R group, more specifically, a
sulfhydryl group. This bond is approximately 60 kilocalories per mole of energy. These
strong covalent bonds result from chemical interaction associated with proteins that fold in
the rough endoplasmic reticulum - this is because reducing agents break disulfide bonds, and
the relatively high concentration of reducing agents in the cytosol break sulfur-sulfur bonds
as soon as the bonds form. The main reducing agent in the cytosol is a tripeptide called
glutathione. The classic Anfinsen experiment is the basis of this understanding. The
experiment utilized ribonuclease, a functional representation of a mature structure with
numerous disulfide bonds. The experiment treated ribonuclease with reducing agents that
denature the protein, specifically urea, which breaks all weak chemical bonds in the protein.
Beta-mercaptoethanol was another reducing agent utilized. The result was a protein with no
biological activity because it no longer had an active site. It is said to be a denatured form of
the ribonuclease protein. The protein was then placed in water with the denaturing agent and
a dialysis tubing. They replaced the external dialysis medium several times to remove as
many denaturing molecules as possible. After dialysis, they found that the ribonuclease
renatured into 100% functional status, which led to the conclusion that the primary structure
determines the tertiary structure.
Biochemical Reactions
The most important proteins in the body are those that help with reactions. These are called
enzymes, and their main job is to help the body generate energy. Reactions are always
possible but not favorable. Approximately 90% of the reactions that occur in the body would
not operate at the appropriate speed required for life. Enzymes, therefore, act as "catalysts."
Approximately 80% of reactions in the body would not occur if not for an enzyme being
present to catalyze the reaction. Enzymes make reactions more probable by making them
easier to occur. They bring substrates together in space and time. Enzymes lower the free
energy of activation, which translates to less energy needed for a reaction to occur. Enzymes
also stabilize the high-energy substrate intermediate within a reaction and are not consumed
in the reaction. An enzyme can be classified as globular if it's a highly folded polypeptide that
often exhibits a spherical shape and is stabilized by weak chemical interactions.
Sources
Protein is a vital part of the human diet and is present in various foods, like eggs, meats,
dairy, seafood legumes, nuts, and seeds. Irrespective of the source of the protein consumed, it
gets broken down in reformed into new proteins in our bodies. These proteins do everything
from fighting infections to helping cells divide. The L-isomer of each amino acid is usually
the more biologically relevant form as compared to the D isomer.
Classification of Amino Acids
While there are hundreds of amino acids in nature, humans use only 20 of them. One way to
further classify them is by defining which one's healthy body can and cannot make.
The three classes of proteins are:
 Non-Essential
 Conditionally Essential
 Essential
Non-Essential Amino Acids
There are five amino acids termed non-essential because they can be obtained from foods and
also generated within the body.
The non-essential amino acids are:
 Alanine
 Asparagine
 Aspartic acid
 Glutamic acid
 Serine
Conditionally-Essential Amino Acids
There are six amino acids termed conditionally essential because healthy bodies can
generate them under normal physiologic conditions. They become essential under certain
conditions like starvation or inborn errors of metabolism.
The conditionally essential amino acids are:
 Arginine
 Cysteine
 Glutamine
 Glycine
 Proline
 Tyrosine
Essential Amino Acids
There are nine amino acids termed essential because they cannot be generated within the
body. Dietary protein, therefore, provides these amino acids, which are needed to make
certain hormones and other important molecules.
The essential amino acids are:
 Histidine
 Isoleucine
 Leucine
 Lysine
 Methionine
 Phenylalanine
 Threonine
 Tryptophan
 Valine

Development
The four levels of protein structure are:
 Primary Structure
 Secondary Structure
 Tertiary Structure
 Quaternary Structure
Primary Structure
Foundationally, a protein is a chain of amino acids bound one to another via peptide bonds.
Similar to a string of beads, these strings can twist and fold into a final protein shape. When
someone eats protein, it will break down into its amino acids. These amino acids are
composed of a central carbon atom bonded to an "amino" or nitrogen-containing group and a
carboxylic "acid" group, hence the name "amino acid." The carbon also has a single hydrogen
atom and a side chain, or "R-group," which is unique to each amino acid. The exception to
this is Proline, which is a ring structure.
Secondary Structure
The secondary structure is the protein structure level at which two common confirmations
occur, alpha-helix and beta-pleated sheets. Biologically, this level can further subdivide into
three common structures. The third is a combination of alpha-helices and beta-plated sheets,
which can form some enzymes.
The first is alpha-helices, which can be present in proteins such as hemoglobin and
intermediate filaments. Alpha helixes are amino acids in a coiled or spiral confirmation,
allowing hydrogen bonding to form between nitrogen and hydrogen, otherwise known as
nitrate groups of one amino acid with the carboxyl group of another amino acid four residues
earlier. Some amino acids are more prone to form alpha helixes. Some examples are
methionine, glutamine, cysteine, histidine, and lysine.
The second is beta-pleated sheets, which appear in fatty acid transport proteins and
antibodies. Beta-pleated sheets are amino acids in a series of adjacent rows, allowing for
lateral hydrogen bonds to form between the amino acid group with the carboxyl group of
another amino acid. When there is a kink in the pattern, it indicates that there is a proline
amino acid located at that position. Some amino acids are more prone to form beta-pleated
sheets. Some examples are isoleucine, tyrosine, tryptophan, and valine.
Furthermore, there are two biological characteristics of secondary structure—those that are
functional and those that are acute phase reactants.
The bone marrow and liver are those classified as functional. The bone marrow produces
immunoglobulins. In the liver, albumin, fibrinogen, and alpha-1-antitrypsin are all produced.
The liver produces approximately 90% of the proteins that serve as the osmotic gradient
within the serum. An osmotic gradient is needed to pull fluid in and out of the capillaries.
The acute phase reactants are those proteins made during inflammation. They are non-
specific and used to monitor whether inflammation is occurring in the body.
Examples include transferrin and ceruloplasmin.
Tertiary Structure
The most critical factor that contributes to the tertiary structure is its hydrophobic and
hydrophilic interactions. The hydrophobic fat-soluble amino acids within a protein will fold
towards the protein's "inside" and away from contact with water. In contrast, hydrophilic
water-soluble amino acid residues will fold towards a protein's "outside," towards contact
with water. Also, tertiary is the level at which covalent bonds form. All of these
characteristics contribute to the three-dimensional shape that ultimately forms.
Quaternary Structure
Quaternary structure is the level at which two or more proteins interact with each other and is
termed cooperativity.
When cooperativity is applied to the composition of enzymes, it classifies as an allosteric
enzyme. Allosteric enzymes are usually rate-limiting enzymes. They are the proteins that
control a specific step within a pathway. The rate-limiting enzyme is therefore involved in the
step that is termed the" rate-limiting step." If the rate-limiting enzyme becomes slower, then
the downstream or subsequent steps also slow down. The vice versa is also true. If the rate-
limiting enzyme becomes more efficient, it will increase its speed of reaction because the
downstream steps ultimately occur sooner. So, by definition, the rate-limiting enzyme should
be the slowest catalyst within the reaction. It also bears mention that most genetic conditions
that are clinically significant affect the rate-limiting enzyme of a biochemical reaction.
The kinetic curve of an enzyme will be shaped in a specific way if the protein is allosteric.
The most likely confirmation is sigmoidal, which is significant in first-order elimination.
While the pharmacokinetic aspects are beyond the scope of this article, one must appreciate
that first-order elimination is associated with substrate concentration and Vmax. When
proteins have multiple active sites, their Vmax increases. Proteins are said to be saturated
when a substrate occupies all active sites. Clinically this is how protein channels and
transporters affect glomerular filtration rate.

Organ Systems Involved

Diet
In general, animal-based protein foods such as eggs, dairy, meat, and seafood provide all nine
of the essential amino acids in adequate amounts. Soy-based foods are unique because they
are tasteless and provide all nine essential amino in sufficient quantities. Most other plant
foods, including whole grains, nuts, legumes, and seeds, possess high levels of some amino
acids and low amounts of others. It would be wrong to assume that animal-based foods
provide more protein than plant-based ones. A cup of tofu contains the same number of
grams of protein as 3 ounces of steak, chicken, or fish. A half-cup of lentils has more grams
of protein than an egg. Not all plant foods are low in the same amino acids, so eating a
variety of plant-based foods can provide all nine of the essentials. For example, pairing
protein sources, like rice and beans or hummus and pita bread or oatmeal topped with almond
butter. However, in terms of volume, it may be necessary to eat more plant-based foods to get
a similar amount of protein and amino acid profile provided by animal-based proteins.
Digestion
When the food reaches the stomach, hydrochloric acid denatures the protein, unfolding it and
making the amino acid chain more accessible to enzymatic action. Then, pepsin, a protein
produced by gastric chief cells, cleaves any available protein into smaller oligopeptide chains,
which then move on into the duodenum. The second set of digestive enzymes, made by the
pancreas, further cleave oligopeptides into tripeptides, dipeptides, and individual amino acids.
These products can all be taken up by intestinal cells where dipeptides and tripeptides convert
into amino acids. Some amino acids are part of the process of synthesizing intestinal enzymes
and new cells. Most enter the bloodstream and are transported to other parts of the body.
Gross Anatomical Manifestation
Hair is a protein that contains a lot of twists and turns. Therefore, it is not surprising that hair
contains many disulfide bonds Heat denatures proteins; this is why individuals may steam
their hair to "relax" and straighten very curly hair. Organ systems in the body
possessing beta-pleated sheets require flat tissues such as flat bones and skin.
Function
Proteins serve crucial roles in human biochemistry. The major role is to provide the body's
building blocks. They are the precursors of several biologically relevant molecules.
Therefore, either the excess or deficiency of protein can lead to disease resulting in nervous
system defects, metabolic problems, organ failure, and even death.
Biochemical Functions
Enzymes proteins accelerate a reaction as a catalyst. Catalyzed reactions are one million or
more times faster. Enzymes usually have the suffix "-ase" in their name. Exceptions are
enzymes discovered before the start of the naming scheme. Each enzyme is regulated by
competitive and noncompetitive inhibitors and/or by allosteric molecules. Enzymes can
catalyze pathways to produce or break down biological molecules. Changes to enzymes can
lead to disease or treatment. Specific amino acids form an enzyme's substrate-binding site. A
substrate-binding site is the "active site." This serves in chemical reactions. Substrates can be
hydrophobic, hydrophilic, charged, uncharged, neutral, or a combination. Mutations that
change amino acids in the active site change the enzyme's activity. A substrate will join an
enzyme that is lined with compatible amino acids. If these amino acids change, a substrate
may not be able to join, therefore rendering an enzyme non-functional. How a substrate
interacts with an active site signifies the "affinity" of that enzyme. Greater affinity means
fewer substrate is needed to achieve a reaction. A mutation that changes the active site can
raise or lower the affinity.
Structural Functions
Proteins serve as the structural elements of cells and tissues—the proteins actin and tubulin
form actin filaments and microtubules. In muscles, actin provides the "scaffolding" against
which myosin can produce muscle contraction.
Kinetic Functions
Motor proteins transport molecules inside a cell, provide movement of certain parts of
individual cells involved in specialized function, generate larger-scale movements of fluids
and semisolids such as the circulation of blood and movement of food through the digestive
tract, and finally provide movement of the human body through their roles in skeletal
muscles. Myosin is a protein with a hydrophobic tail, a head group that can attach and detach
from actin filaments, and a "hinge" section, which moves the head group back and forth,
resulting in movement.
Channels
Channels are essential for the transportation of nutrients into and out of cells for nerve signals
and the selective filtration of molecules in the kidneys. This is exemplified in how the
mammalian cell has an intracellular potassium concentration of approximately 140
millimoles per cell and sodium of 5 to 15 millimoles. The extracellular environment has a
potassium concentration of 5 moles and a sodium concentration of 145 millimoles.
Potassium-specific channels are responsible for regulating these concentrations in their
respective compartments.
Mechanism
Translation
Protein synthesis is initiated by GTP, which causes ribosomal units to assemble and begin the
elongation process, which turns the primary transcript into the amino acid sequence forming
the fundamental structure of a protein. Eukaryotic ribosomal subunits are in the 40s and 60s,
whereas prokaryotic ribosomal subunits are 30s and 50s. The eukaryotic ribosomal subunit is
in the 80s. The prokaryotic ribosomal subunit is in the 70s. The s does not represent the size
of the subunits, so, therefore, one must not assume that the total for a subunit complex is the
sum of the two individual subunits. The” s” represents the sedimentation coefficient at which
each protein exhibits when subjected to centrifugation. The process of elongation is how the
primary structure of a protein is made, which is also known as translocation. A tRNA binds to
a specific position termed the site. The TRNA then translocates to the pea site, delivering the
amino acid to the end of a growing polypeptide chain. Finally, the tRNA moves to the e-site,
where it will exit.

Related Testing
Protein Sequencing
There are several laboratory methods used to determine the characteristics of a protein. These
are tests that determine the type, amount, and charge of the amino acids in a protein.
Acid Hydrolysis
 Used to determine the types of amino acids in a protein.
 This method cannot determine the sequence.
 Acid hydrolysis is performed by dipping a protein into acid, which denatures the
protein.

Gel Electrophoresis
 Uses agarose gel to separate proteins primarily by size.
 It can also separate them by charge if electrodes are added.
 Smaller proteins migrate further.
 Larger proteins stay closer to the start site.
 It does not sequence proteins.
  There is an electrophoretic pattern for any polypeptide; therefore, gel electrophoresis
can be used to detect it.

Ninhydrin Reaction
 It is a chemical reaction that reacts with an amino acid on the amino-terminal (left).
 Reacts with all amino acids creating a purple color.
 The proline reaction creates a yellow color.
 Used to count the number of prolines in a specific protein.

Pathophysiology
A dysfunctional protein can lead to a variety of medical conditions and, often, death.
Dysfunctional proteins can lead to childhood obesity, the breakdown of the retina leading to
blindness, hearing loss, and type 2 diabetes.
Take, for example, the protein cilia and how its dysfunction manifests.
  Inadequate cilia in flagella lead to sperm dysmotility.
 Defective cilia in the respiratory tract lead to chronic lung infections.
 Eustachian tube cilia dysfunction causes chronic ear infections and hearing loss.
 Dysfunctional cilia in the Fallopian tubes cause infertility.
Infectious
Many infective agents work by mimicking human accessory proteins and binding to
elongation factors. Although the bacteria inhibit proteins, viruses actually "hijack" and use
the host's protein synthesis machinery for reproduction and further infection. Infectious,
misfolded proteins called "prions," short for "proteinaceous and infectious virions," infect as
a normally folded protein and then replicate and misfold into β-sheets called an "amyloid
fold." These aggregate into amyloid plaques and create "holes" in tissue creating a
"spongiform" appearance. Prions affect nervous tissue leading to harmful and deadly
neurological symptoms.
Cartilaginous
Mutations that alter collagen's structure promote frequent fractures, easy bruising, weak
joints, and hearing loss due to abnormal inner ear bones.
Enzymatic
A genetic disease can cause a deficiency of the enzyme required to convert amino acids into
neurotransmitters and skin pigment. The disease does not result from the decrease in amino
acid levels, but rather from the high concentration of amino acids. This promotes activity in a
minor enzymatic pathway producing toxic products. The presence of these products is
screened for in the blood as part of standard neonatal testing. Patients usually express traits
of albinism, white-blond hair, pale blue eyes, and an odor from the toxic products in their
sweat, urine, skin, and hair. Treatment of this disease is with a diet low in specific amino
acids.
Muscular
Diseases in skeletal muscle proteins may cause a rapid breakdown, therefore resulting in
the inability to walk.
Osmotic
Misfolded proteins can cause numerous, clinically significant diseases. Most notable is cystic
fibrosis, an autosomal recessive disorder due to a defect in the chloride channel CFTR
protein, which regulates water, chloride movement, and mucus production. Normally this
protein is a channel for chloride to move out of cells to balance the tonicity of salt and water.
Sodium is an ion that moves in a counter-current fashion to balance the osmolality between
compartments. This is important in glandular tissues that secrete large concentrations of
sodium chloride. Mucus plugs, recurrent infections, infertility, and gastrointestinal
dysfunction are common manifestations.
Multifactorial
Acute phase reactants are caused mostly by IL-6 made by macrophages and also T-helper
cells. Too many acute-phase proteins can be deposited anywhere in the body. The non-
specific deposition is called amyloidosis. Deposition into the vasculature alters their integrity.
Compliance with blood vessel walls will decrease, leading to less distensibility; this makes
the blood vessel more likely to rupture if the pressure goes up—a massive intracerebral
hemorrhage in a young person with no prior history of hypertension or trauma. Diagnostic
confirmation is via congo red stain, which shows a characteristic apple-green birefringence.
Beta-amyloid or tau protein is present in both age-related and Down syndrome-related
Alzheimer's disease (beta-lipoprotein E4 is more specific for Alzheimer's disease). In the
general population, this protein gets oxidized, causing Alzheimer's disease. Neurofibrillary
tangles are the manifestation of the tau protein undergoing oxidation and aggregating. In
Down syndrome, the body cannot cleave the beta-lipoprotein from the amyloid precursor
protein. The result is the build-up of beta lipoprotein, which causes early-onset Alzheimer's
disease.
Lecture Activity: DECODING
DNA CODING
A sequence of DNA is transcribed into an RNA sequence. This RNA sequence reads 5′-
GCUUUCACGCAC-3′. Use the codon wheel provided to determine the sequence of amino
acids. [A] Arg, Ser, Thr, Pro [B] Ser, Leu, Ala, His [C] Ala, Phe, Thr, His [D] Ser, Leu, Ala,
Gln [E] Ala, Leu, Thr, Gln.

A sequence of DNA is transcribed into an RNA sequence. This RNA sequence reads from
five prime to three prime GCUUUCACGCAC. Use the codon wheel provided to determine
the sequence of amino acids. Arginine, serine, threonine, proline. Serine, leucine, alanine,
histidine. Alanine, phenylalanine, threonine, histidine. Serine, leucine, alanine, glutamine. Or
alanine, leucine, threonine, glutamine.

This question is asking us about how to translate a sequence of mRNA into the corresponding
amino acids. Before we can answer this, let’s clear the answer choices and review some key
points.

Let’s say our cell here needs to produce insulin. The gene for insulin is located here in pink in
the cell’s DNA. For this cell to produce insulin or any other protein, it must go through two
processes called transcription and translation. During transcription, the gene for the protein is
transcribed or copied to produce what’s called messenger RNA or mRNA. This messenger
RNA is a message for the cell that tells it that it needs to make the protein, or insulin in this
case.

Transcription is the process of converting a section of double-stranded DNA or our insulin

gene shown here in pink into a single-stranded mRNA molecule. Like DNA, the sequence for
mRNA is written in the five-prime to three-prime direction and contains four different
nucleotides or bases: adenine or A for short, guanine, and cytosine, but instead of thymine,
which is in DNA, RNA uses uracil or U for short.

After transcription, the sequence in the mRNA molecule can be translated into its
corresponding amino acids. This step is called translation, and it forms a polypeptide with
each of these colored circles representing a different amino acid. This polypeptide can then
fold to form its corresponding protein, or insulin in this example.
Now that we’ve covered transcription and translation, let’s turn our attention to this mRNA
sequence in question and describe how this specific sequence can be translated into amino
acids.

An mRNA sequence is translated into groups of three nucleotides called a codon. A codon is
a sequence of three nucleotides that code for an amino acid. Codons are always read in a way
that they do not overlap. So, in this sequence, this is the first codon, this is the second codon,
this is the third codon, and here’s the last codon. So, this mRNA sequence has four codons.

Now, to translate the sequence of nucleotides into its corresponding amino acid, we need to
use a codon wheel, like the one shown on the left. To use the codon wheel, we start from the
inside. This corresponds to the five-prime end of the codon. And we work our way outwards
to the three-prime end of the codon. So, for this codon, we’ll be working from the five-prime
to the three-prime end.

So, with the codon GCU, we start with G, then we move over to C, and finally, we land on U.
So, the codon GCU corresponds to the amino acid alanine. Then, for the next codon UUC, we
do the same thing. So, the first nucleotide is U, then U again, and then C. This corresponds to
the amino acid phenylalanine. Then, for the codon ACG, this corresponds to threonine. And
finally, the codon CAC corresponds to the amino acid histidine. Therefore, the corresponding
amino acid sequence for the given mRNA sequence is alanine, phenylalanine, threonine, and
histidine.
References:

1.
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