Professional Documents
Culture Documents
Submitted by:
Submitted to:
May 7,2019
A. THE CENTRAL DOGMA
Two essential features of living creatures are the ability to reproduce their own genome
and manufacture their own energy. To accomplish these feats, an organism must be able to
make proteins using information encoded in its DNA. Proteins are essential for cellular
architecture, giving the cell a particular shape and structure. Proteins include enzymes that
catalyze reactions used to make energy. Proteins control cellular processes like replication.
Proteins provide channels in the membrane for cells to communicate with each other or share
metabolites. Making proteins is a key operation for all living organisms. The central dogma
of molecular biology states that information flows from DNA to RNA to protein. (Clark &
Pazdernik, 2016)
B. DNA REPLICATION
DNA Replication
DNA replication occurs as a prelude to cell division in both prokaryotes and
eukaryotes. This phase in the DNA replication is called the S phase or the synthesis phase.
The two daughter DNA molecules formed from replication eventually become chromosomes
in their own right in the daughter cells.
As with all phenomena that involve nucleic acids, the basic machinery of DNA
replication depends on complementarity of DNA molecules and on the ability of proteins to
form specific interactions with DNA of specific sequences.
Watson and Crick Model
The model of DNA replication proposed by Watson and Crick is based on the
hydrogen-bonded specificity of the base pairs. Complementary strands are shown in different
colors. The fact that new strands can grow only in the 5’(five prime)-to-3’(3 prime) direction
adds complexities to the detailed mechanism of replication.
If this model is correct, then each daughter molecule should contain one parental
nucleotide chain and one newly synthesized nucleotide chain. This prediction has been tested
in both prokaryotes and eukaryotes. A little thought shows that there are at least three
different ways in which a parental DNA molecule might be related to the daughter molecules.
These hypothetical modes are called semiconservative (the Watson-Crick model),
conservative, and dispersive
DNA Replication Patterns
In semiconservative replication, each daughter duplex contains one parental and one
newly synthesized strand. In conservative replication, on the other hand, one daughter duplex
consists of two newly synthesized strands, and the parent duplex is conserved. Dispersive
replication results in daughter duplexes that consist of strands containing only segments of
parental DNA and newly synthesized DNA.
THE TRANSCRIPTION
Transcription involves the synthesis of an RNA transcript complementary to one
strand of DNA of a gene. During replication entire genome is copied but in transcription
only the selected portion of genome is copied. During transcription, one strand of DNA of a
gene is used as a template to synthesize a complementary strand of RNA, called the gene
transcript. For example, in the figure below, the DNA strand containing the nucleotide
sequence AAA is used as a template to produce the complementary sequence UUU in the
RNA transcript.
The RNA molecules that are translated on ribosomes are called messenger RNAs
(mRNAs). In prokaryotes, the product of transcription, the primary transcript, usually is
equivalent to the mRNA molecule.
If the RNA molecule is an mRNA, it will specify amino acids in the protein gene
product. Therefore, mRNA molecules are coding strands of RNA. They are also called sense
strands of RNA because their nucleotide sequences “make sense” in that they specify
sequences of amino acids in the protein gene products. An RNA molecule that is
complementary to an mRNA is referred to as antisense RNA.
TRANSCRIPTION IN PROKARYOTES
INITIATION
Prokaryotic RNA Polymerase
Prokaryotes use the same RNA polymerase to transcribe all of their genes. In E. coli,
the polymerase is composed of five polypeptide subunits, two of which are identical. Four of
these subunits, denoted α, α, β, and β′ comprise the polymerase core enzyme. These subunits
assemble every time a gene is transcribed, and they disassemble once transcription is
complete. The polymerase comprised of all five subunits is called the holoenzyme.
The holoenzyme, has the composition α2ββ′σ.
The α subunits are involved in the assembly of the tetrameric core (α2ββ′) of RNA
polymerase.
The β subunit contains the ribonucleoside triphosphate binding site.
The β′ subunit harbors the DNA template-binding region.
The sigma (σ) factor is involved only in the initiation of transcription; it plays no role
in chain elongation.
After RNA chain initiation has occurred, the σ factor is released, and chain elongation is
catalyzed by the core enzyme (α2ββ′). The function of sigma (σ) is to recognize and bind
RNA polymerase to the transcription initiation or promoter sites in DNA.
INITIATION
Unlike their prokaryotic counterparts, eukaryotic RNA polymerases cannot initiate
transcription by themselves. All five eukaryotic RNA polymerases require the assistance of
protein transcription factors to start the synthesis of an RNA chain. These transcription
factors must bind to a promoter region in DNA and form an appropriate initiation complex
before RNA polymerase will bind and initiate transcription.
Different promoters and transcription factors are utilized by RNA polymerases. In this
report, we focus on the initiation of pre-mRNA synthesis by RNA polymerase II, which
transcribes the vast majority of eukaryotic genes.
The promoters recognized by RNA polymerase II consist of short conserved elements,
or modules, located upstream from the transcription startpoint. The conserved element closest
to the transcription start site (position +1) is called the TATA box; it has the consensus
sequence TATAAAA (reading 5′ to 3′ on the nontemplate strand) and is centered at about
position -30. The TATA box plays an important role in positioning the transcription
startpoint. The second conserved element is called the CAAT box; it usually occurs near
position -80 and has the consensus sequence GGCCAATCT.
Two other conserved elements, the GC box, consensus GGGCGG, and the octamer
box, consensus ATTTGCAT, often are present in RNA polymerase II promoters.
The initiation of transcription by RNA polymerase II requires the assistance of several
basal transcription factors. Basal transcription factors are necessary for RNA polymerase to
function at a site of transcription in eukaryotes. They are considered the most basic set of
proteins needed to activate gene transcription. Each basal transcription factor is denoted
TFIIX (Transcription Factor X for RNA polymerase II, where X is a letter identifying the
individual factor).
TFIID is the first basal transcription factor to interact with the promoter; it contains a
TATA-binding protein (TBP) and several small TBP-associated proteins.
TFIIE then joins the initiation complex, binding to the DNA downstream from the
transcription startpoint.
Two other factors, TFIIH and TFIIJ, join the complex after TFIIE, but their locations
in the complex are unknown.
ELONGATION OF RNA CHAIN
RNA polymerases catalyze RNA chain elongation by the same mechanism as the
RNA polymerases of prokaryotes. Early in the elongation process, the 5ends of eukaryotic
pre-mRNAs are modified by the addition of 7-methyl guanosine (7-MG) caps. These 7-MG
caps are added when the growing RNA chains are only about 30 nucleotides long. The 7-MG
cap contains an unusual 5′-5′ triphosphate linkage and two or more methyl groups. The 7-MG
caps are recognized by protein factors involved in the initiation of translation and also help
protect the growing RNA chains from degradation by nucleases.
For polynucleotide synthesis to occur, the transcription machinery needs to move
histones out of the way every time it encounters a nucleosome. This is accomplished by a
special protein dimer called FACT, which stands for “facilitates chromatin transcription.”
FACT partially disassembles the nucleosome immediately ahead (upstream) of a transcribing
RNA Polymerase II by removing two of the eight histones (a single dimer of H2A and H2B
histones is removed.) This presumably sufficiently loosens the DNA wrapped around that
nucleosome so that RNA Polymerase II can transcribe through it. FACT reassembles the
nucleosome behind the RNA Polymerase II by returning the missing histones to it. RNA
Polymerase II will continue to elongate the newly-synthesized RNA until transcription
terminates.
TERMINATION
In the case of protein-encoding genes, the cleavage site which determines the “end”
of the emerging pre-mRNA occurs between an upstream AAUAAA sequence and a
downstream GU-rich sequence separated by about 40-60 nucleotides in the emerging RNA.
Once both of these sequences have been transcribed, a protein called CPSF (cleavage and
polyadenylation factor) in humans binds the AAUAAA sequence and a protein called CstF
(cleavage stimulation factor) in humans binds the GU-rich sequence. These two proteins
form the base of a complicated protein complex that forms in this region before CPSF cleaves
the nascent pre-mRNA at a site 10-30 nucleotides downstream from the AAUAAA site.
Endonucleases are enzymes that cleave the phosphodiester bond within a polynucleotide
chain.
After cleavage, the enzyme poly(A) polymerase adds poly(A) tails, tracts of
adenosine monophosphate residues about 200 nucleotides long, to the 3′ ends of the
transcripts. (Simmons & Snustad, 2012)
D. METABOLIC REGULATION
In examining the various pathways for the catabolism and anabolism of the major
metabolic fuels and building blocks in mammals—carbohydrates, fatty acids, amino acids,
and nucleotides—we have seen that biosynthetic and degradative pathways differ for
thermodynamic reasons. These pathways are also regulated so that their simultaneous
operation does not waste resources.
Regulation by Compartmentation
Compartmentation makes possible the simultaneous, but separate, operation and
regulation of similar pathways. Furthermore, pathway activities can be coordinated through
regulation of the transport of metabolities and coenzymes between cell compartments.
Suppose two pathways in different cell compartments require NAD for activity. The
distribution of NAD between the two compartments will then determine the relative activity
of these competing pathways, and the pathway with access to the most NAD will be favored.
Metabolites Travel Between Organs
The body’s organs are connected to each other by the circulatory system so that
metabolites synthesized by one organ, such as glucose produced by the liver, can easily reach
other tissues. Amino acids released from various tissues travel to the liver or kidney for
disposal of their amino groups.
Some metabolic pathways are circuits that include inter-organ transport. For example,
the Cori cycle (named after Carl and Gerty Cori, who first described it) is a metabolic
pathway involving the muscles and liver. During periods of high activity, muscle glycogen is
broken down to glucose, which undergoes glycolysis to produce the ATP required for muscle
contraction. The rapid catabolism of muscle glucose exceeds the capacity of the mitochondria
to reoxidize the resulting NADH and so generates lactate as an end product.
A second inter-organ pathway, the glucose–alanine cycle, also links the muscles and
liver. During vigorous exercise, muscle proteins break down, and the resulting amino acids
undergo transamination to generate intermediates to boost the activity of the citric acid cycle.
E. HOW THE CELL SENSES ITS EXTRACELLULAR ENVIRONMENT
What is Extracellular Environment?
According to the gene ontology database, the extracellular is defined as: “That part of
a multicellular organism outside the cells proper, usually taken to be outside the plasma
membranes and occupied by fluid”. In cell biology, molecular biology and related fields, the
word extracellular means “outside the cell”. This is usually taken to be outside the plasma
membranes and occupied by fluid. The term is used in contrast to intracellular. “inside the
cell”.
Extracellular Environment is all constituents of the body located outside the cell.
Look at the picture above, we’ll have transmission of materials that goes from intracellular
fluid in tissue cells to body organs and so cells communicate with each other by secreting
different chemical regulators in the extracellular environment. Chemical regulators are
hormones produce by the cells. 67% of our water comes from intracellular and 33% is going
to come from extracellular fluid compartment. The 20% water of extracellular compartment
is found within the blood plasma but the remaining 80% of extracellular compartment comes
from interstitial fluid and/or commonly known as tissue fluid. This tissue fluid is what
connects the inner cellular with the blood and this where help waste products that are going to
exit out, cell will have ions coming in and out, water coming in and out, different nutrients
that are going to come in to the cells will have CO2, a waste product that are going to leave
the cells and oxygen which is going to enter into cell. Cell constantly receive cues from
extracellular environment and respond by changing cytoskeletal organization and cellular
functions as well as initiating transcriptional program, thereby maintaining homeostasis.
Homeostasis perform the dynamic balance of what’s coming in and out of the cell.
What are Cell Senses?
What we sense informs who we are. Humans have five (5) senses: touch, taste, smell,
sight and hearing. The senses are based on receptor cells or group of receptor cells called
sense organs. Receptor respond to stimuli and send nerve impulses along sensory neurons.
The brain interprets the nerve impulse and thus, perceive the impulse as one of our senses.
But how we experience our five major special senses? All boils down to one thing: sensory
cells translating chemical, electromagnetic, and mechanical stimuli into action potentials that
our nervous system can make sense of. This process is called transduction, and each sense
works in its own way.
Sight
Our vision functions with the help of photoreceptors, cells that detect light waves.
Touch and Hearing
Touch and hear as well with balance use mechanoreceptors that detect sound waves
and pressure on the skin and in the inner ear.
Taste and Smell
Taste or gustation and smell of olfaction are chemical senses. They call on
chemoreceptors in our taste buds and nasal passages to detect molecules in our food and the
air around us.
References
Clark, D. & Pazdernik, N. (2016). Biotechnology: applying the genetic revolution. Waltham,
MA: Elsevier Inc.
Discher DE, Janmey P, Wang YI (2005). Tissue cells feel and respond to the stiffness of their
substance. Science 310: 1139-1143.
Simmons, M. & Snustad, P. (2012). Principles of genetics, sixth edition. Hoboken, NJ: John
Wiley & Sons, Inc.,
http://leavingbio.net/senses/
https://www.nature.com/scitable/ebooks/essentials-of-cell-biology-14749010/how-do-cells-
sense-their-environment-14751787
http://oerpub.github.io/epubjs-demo-book/content/m46021.xhtml
https://www.slideshare.net/drimhotep/ivmsinteractions-between-cells-and-the-extracellular-
environment
http://saggymouse.tara.tsukuba.ac.jp/en/
http://anatomyandphysiologyi.com/body-fluids/