This document discusses gene regulation in prokaryotes. It begins by introducing the concept of gene regulation and how only a fraction of genes are expressed at any given time. It then discusses several key examples of gene regulation in prokaryotes, including the lac, trp, and arabinose operons. The lac operon regulates lactose metabolism in E. coli in response to glucose and lactose availability. The trp operon regulates tryptophan synthesis using both repression and attenuation. The arabinose operon regulates arabinose metabolism using both positive and negative regulation by the AraC protein. The document also briefly discusses the SOS response, stringent response, and gene regulation in bacteriophage lambda.
Most bacteria are free-living organisms that grow by increasing
in mass and then divide by binary fission.
Growth and division are controlled by genes, the expression
of which must be regulated appropriately. Genes
whose activity is controlled in response to the needs of a
cell or organism are called regulated genes. All organisms
also have a large number of genes whose products
are essential to the normal functioning of a growing and
dividing cell, no matter what the conditions are. These
genes are always active in growing cells and are known as
constitutive genes or housekeeping genes; examples include
genes that code for the enzymes needed for protein
synthesis and glucose metabolism. Note that all genes are
regulated on some level. If normal cell function is impaired
for some reason, the expression of all genes, including
constitutive genes, is reduced by regulatory
mechanisms. Thus, the distinction between regulated
and constitutive genes is somewhat arbitrary.
Most bacteria are free-living organisms that grow by increasing
in mass and then divide by binary fission.
Growth and division are controlled by genes, the expression
of which must be regulated appropriately. Genes
whose activity is controlled in response to the needs of a
cell or organism are called regulated genes. All organisms
also have a large number of genes whose products
are essential to the normal functioning of a growing and
dividing cell, no matter what the conditions are. These
genes are always active in growing cells and are known as
constitutive genes or housekeeping genes; examples include
genes that code for the enzymes needed for protein
synthesis and glucose metabolism. Note that all genes are
regulated on some level. If normal cell function is impaired
for some reason, the expression of all genes, including
constitutive genes, is reduced by regulatory
mechanisms. Thus, the distinction between regulated
and constitutive genes is somewhat arbitrary.
REGULATION OF
GENE EXPRESSION
IN PROKARYOTES & EUKARYOTES .
This presentation is enriched with lots of information of gene expression with many pictures so that anyone can understand gene expression easily.
Gene expression is the process by which the information encoded in a gene is used to direct the assembly of a protein molecule.
Gene expression is explored through a study of protein structure and function, transcription and translation, differentiation and stem cells.
It is the process by which information from a gene is used in the synthesis of a functional gene product.
These products are often proteins, but in non-protein coding genes such as ribosomal RNA (rRNA), transfer RNA (tRNA) or small nuclear RNA (snRNA) genes, the product is a functional RNA.
The process of gene expression is used by all known life - eukaryotes (including multicellular organisms), prokaryotes (bacteria and archaea)
Regulation of gene expression:
Regulation of gene expression includes a wide range of mechanisms that are used by cells to increase or decrease the production of specific gene products (protein or RNA).
Gene regulation is essential for viruses, prokaryotes and eukaryotes as it increases the versatility and adaptability of an organism by allowing the cell to express protein when needed.
CLASSIFICATION OF GENE WITH RESPECT TO THEIR EXPRESSION:
Constitutive ( house keeping) genes:
Are expressed at a fixed rate, irrespective to the cell condition.
Their structure is simpler.
Controllable genes:
Are expressed only as needed. Their amount may increase or decrease with respect to their basal level in different condition.
Their structure is relatively complicated with some response elements.
TYPES OF REGULATION OF GENE:
positive & negative regulation.
Steps involving gene regulation of prokaryotes & eukaryotes.
Operon-structure,classification of mechanisms- lac operon,tryptophan operon ,
and many things related to gene expression.
This is a video slide so anyone can understand this topic easily by seeing pictures included in this slide.
Arabinose operon and their regulation and arac VijiMahesh1
arabinose operon and their detalied explanation about the operon conceptt and their regulation both positive and negative and the detailed explanation of the promoter ,operator,inducer,structural gene,arac protein
lac operon is a negatively controlled inducible operon.E.coli can use lactose as a source of carbon.
The enzymes required for the use of lactose as a source of carbon are synthesised only when the lactose is available as carbon source.
The lac operon is an example of nagatively controlled inducible operon.
Structure
The lac operon consists of 5 structural units.
Promoter
Operator
Structural genes
CAP binding sites
Regulatory gene
Gene regulation in eukaryotes in a nutshell covering all the important stages of gene regulation in eukaryotes at transcriptional level, translation level and post-translational level.
Introduction
Cre-lox recombination
Cre-lox system- Cre recombinase , loxP site
FLP-FRT recombination
FLP-FRT system- FLP recombinase , FRT site
Mechanism of Cre-lox and FLP-FRT recombination
Binding
Synapsis , cleavage and strand exchange
Three type of arrangement
Inversion
Translocation/ Insersion
Deletion
Application of Cre-lox and FLP-FRT recombination
Disadvantage of FLP-FRT
Advantage and disadvantage of Cre-lox
Conclusion
References
Imagine a situation when a cell starts producing enzymes required for metabolism and those required for cell death (apoptosis) at the same time. The cell will be in a confused state and will not know which function to perform first. The needs of the body keep changing with time and cell has to tune itself to perform the desired set of activities. Gene regulation helps a unicellular organism to adapt well to the environment.
REGULATION OF
GENE EXPRESSION
IN PROKARYOTES & EUKARYOTES .
This presentation is enriched with lots of information of gene expression with many pictures so that anyone can understand gene expression easily.
Gene expression is the process by which the information encoded in a gene is used to direct the assembly of a protein molecule.
Gene expression is explored through a study of protein structure and function, transcription and translation, differentiation and stem cells.
It is the process by which information from a gene is used in the synthesis of a functional gene product.
These products are often proteins, but in non-protein coding genes such as ribosomal RNA (rRNA), transfer RNA (tRNA) or small nuclear RNA (snRNA) genes, the product is a functional RNA.
The process of gene expression is used by all known life - eukaryotes (including multicellular organisms), prokaryotes (bacteria and archaea)
Regulation of gene expression:
Regulation of gene expression includes a wide range of mechanisms that are used by cells to increase or decrease the production of specific gene products (protein or RNA).
Gene regulation is essential for viruses, prokaryotes and eukaryotes as it increases the versatility and adaptability of an organism by allowing the cell to express protein when needed.
CLASSIFICATION OF GENE WITH RESPECT TO THEIR EXPRESSION:
Constitutive ( house keeping) genes:
Are expressed at a fixed rate, irrespective to the cell condition.
Their structure is simpler.
Controllable genes:
Are expressed only as needed. Their amount may increase or decrease with respect to their basal level in different condition.
Their structure is relatively complicated with some response elements.
TYPES OF REGULATION OF GENE:
positive & negative regulation.
Steps involving gene regulation of prokaryotes & eukaryotes.
Operon-structure,classification of mechanisms- lac operon,tryptophan operon ,
and many things related to gene expression.
This is a video slide so anyone can understand this topic easily by seeing pictures included in this slide.
Arabinose operon and their regulation and arac VijiMahesh1
arabinose operon and their detalied explanation about the operon conceptt and their regulation both positive and negative and the detailed explanation of the promoter ,operator,inducer,structural gene,arac protein
lac operon is a negatively controlled inducible operon.E.coli can use lactose as a source of carbon.
The enzymes required for the use of lactose as a source of carbon are synthesised only when the lactose is available as carbon source.
The lac operon is an example of nagatively controlled inducible operon.
Structure
The lac operon consists of 5 structural units.
Promoter
Operator
Structural genes
CAP binding sites
Regulatory gene
Gene regulation in eukaryotes in a nutshell covering all the important stages of gene regulation in eukaryotes at transcriptional level, translation level and post-translational level.
Introduction
Cre-lox recombination
Cre-lox system- Cre recombinase , loxP site
FLP-FRT recombination
FLP-FRT system- FLP recombinase , FRT site
Mechanism of Cre-lox and FLP-FRT recombination
Binding
Synapsis , cleavage and strand exchange
Three type of arrangement
Inversion
Translocation/ Insersion
Deletion
Application of Cre-lox and FLP-FRT recombination
Disadvantage of FLP-FRT
Advantage and disadvantage of Cre-lox
Conclusion
References
Imagine a situation when a cell starts producing enzymes required for metabolism and those required for cell death (apoptosis) at the same time. The cell will be in a confused state and will not know which function to perform first. The needs of the body keep changing with time and cell has to tune itself to perform the desired set of activities. Gene regulation helps a unicellular organism to adapt well to the environment.
The following topics are discussed
. Prokaryotic gene expression and regulation
Prokaryotic “gene structure”
The basic structure of Operon
Lactose Operon” regulation
Tryptophan Operon” regulation
2. Eukaryotic gene expression and regulation
Eukaryotic gene structure
Regulons
Regulation of gene expression in prokaryotes finalICHHA PURAK
The power point presentation explains about regulation of gene expression in prokaryotes by means of Inducible and repressible operons with the help of Lactose(lac) operon and Tryptophan (trp)
Transcription and the control of gene expression [Autosaved].pptxAbdullahAli647576
The first genetic maps, constructed in the organisms
such as the fruit fly, used genes as markers.
• The only genes that could be studied were those
specifying phenotypes that were distinguishable by
visual examination. Eg. Eye color, height.
• Some organisms have very few visual characteristics
so gene mapping with these organisms has to rely on
biochemical phenotypes
Gene regulation can be defined as any kind of alteration in the gene to give rise to a different expression which might result in a change in the synthesized amino acid sequence.”
Gene expression is basically the synthesis of the polypeptide chain encoded by a particular gene.
Therefore the expression of the gene can be quantified in terms of the amount of protein synthesised by the genes.
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New Directions in Targeted Therapeutic Approaches for Older Adults With Mantl...i3 Health
i3 Health is pleased to make the speaker slides from this activity available for use as a non-accredited self-study or teaching resource.
This slide deck presented by Dr. Kami Maddocks, Professor-Clinical in the Division of Hematology and
Associate Division Director for Ambulatory Operations
The Ohio State University Comprehensive Cancer Center, will provide insight into new directions in targeted therapeutic approaches for older adults with mantle cell lymphoma.
STATEMENT OF NEED
Mantle cell lymphoma (MCL) is a rare, aggressive B-cell non-Hodgkin lymphoma (NHL) accounting for 5% to 7% of all lymphomas. Its prognosis ranges from indolent disease that does not require treatment for years to very aggressive disease, which is associated with poor survival (Silkenstedt et al, 2021). Typically, MCL is diagnosed at advanced stage and in older patients who cannot tolerate intensive therapy (NCCN, 2022). Although recent advances have slightly increased remission rates, recurrence and relapse remain very common, leading to a median overall survival between 3 and 6 years (LLS, 2021). Though there are several effective options, progress is still needed towards establishing an accepted frontline approach for MCL (Castellino et al, 2022). Treatment selection and management of MCL are complicated by the heterogeneity of prognosis, advanced age and comorbidities of patients, and lack of an established standard approach for treatment, making it vital that clinicians be familiar with the latest research and advances in this area. In this activity chaired by Michael Wang, MD, Professor in the Department of Lymphoma & Myeloma at MD Anderson Cancer Center, expert faculty will discuss prognostic factors informing treatment, the promising results of recent trials in new therapeutic approaches, and the implications of treatment resistance in therapeutic selection for MCL.
Target Audience
Hematology/oncology fellows, attending faculty, and other health care professionals involved in the treatment of patients with mantle cell lymphoma (MCL).
Learning Objectives
1.) Identify clinical and biological prognostic factors that can guide treatment decision making for older adults with MCL
2.) Evaluate emerging data on targeted therapeutic approaches for treatment-naive and relapsed/refractory MCL and their applicability to older adults
3.) Assess mechanisms of resistance to targeted therapies for MCL and their implications for treatment selection
Prix Galien International 2024 Forum ProgramLevi Shapiro
June 20, 2024, Prix Galien International and Jerusalem Ethics Forum in ROME. Detailed agenda including panels:
- ADVANCES IN CARDIOLOGY: A NEW PARADIGM IS COMING
- WOMEN’S HEALTH: FERTILITY PRESERVATION
- WHAT’S NEW IN THE TREATMENT OF INFECTIOUS,
ONCOLOGICAL AND INFLAMMATORY SKIN DISEASES?
- ARTIFICIAL INTELLIGENCE AND ETHICS
- GENE THERAPY
- BEYOND BORDERS: GLOBAL INITIATIVES FOR DEMOCRATIZING LIFE SCIENCE TECHNOLOGIES AND PROMOTING ACCESS TO HEALTHCARE
- ETHICAL CHALLENGES IN LIFE SCIENCES
- Prix Galien International Awards Ceremony
Report Back from SGO 2024: What’s the Latest in Cervical Cancer?bkling
Are you curious about what’s new in cervical cancer research or unsure what the findings mean? Join Dr. Emily Ko, a gynecologic oncologist at Penn Medicine, to learn about the latest updates from the Society of Gynecologic Oncology (SGO) 2024 Annual Meeting on Women’s Cancer. Dr. Ko will discuss what the research presented at the conference means for you and answer your questions about the new developments.
MANAGEMENT OF ATRIOVENTRICULAR CONDUCTION BLOCK.pdfJim Jacob Roy
Cardiac conduction defects can occur due to various causes.
Atrioventricular conduction blocks ( AV blocks ) are classified into 3 types.
This document describes the acute management of AV block.
Title: Sense of Taste
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the structure and function of taste buds.
Describe the relationship between the taste threshold and taste index of common substances.
Explain the chemical basis and signal transduction of taste perception for each type of primary taste sensation.
Recognize different abnormalities of taste perception and their causes.
Key Topics:
Significance of Taste Sensation:
Differentiation between pleasant and harmful food
Influence on behavior
Selection of food based on metabolic needs
Receptors of Taste:
Taste buds on the tongue
Influence of sense of smell, texture of food, and pain stimulation (e.g., by pepper)
Primary and Secondary Taste Sensations:
Primary taste sensations: Sweet, Sour, Salty, Bitter, Umami
Chemical basis and signal transduction mechanisms for each taste
Taste Threshold and Index:
Taste threshold values for Sweet (sucrose), Salty (NaCl), Sour (HCl), and Bitter (Quinine)
Taste index relationship: Inversely proportional to taste threshold
Taste Blindness:
Inability to taste certain substances, particularly thiourea compounds
Example: Phenylthiocarbamide
Structure and Function of Taste Buds:
Composition: Epithelial cells, Sustentacular/Supporting cells, Taste cells, Basal cells
Features: Taste pores, Taste hairs/microvilli, and Taste nerve fibers
Location of Taste Buds:
Found in papillae of the tongue (Fungiform, Circumvallate, Foliate)
Also present on the palate, tonsillar pillars, epiglottis, and proximal esophagus
Mechanism of Taste Stimulation:
Interaction of taste substances with receptors on microvilli
Signal transduction pathways for Umami, Sweet, Bitter, Sour, and Salty tastes
Taste Sensitivity and Adaptation:
Decrease in sensitivity with age
Rapid adaptation of taste sensation
Role of Saliva in Taste:
Dissolution of tastants to reach receptors
Washing away the stimulus
Taste Preferences and Aversions:
Mechanisms behind taste preference and aversion
Influence of receptors and neural pathways
Impact of Sensory Nerve Damage:
Degeneration of taste buds if the sensory nerve fiber is cut
Abnormalities of Taste Detection:
Conditions: Ageusia, Hypogeusia, Dysgeusia (parageusia)
Causes: Nerve damage, neurological disorders, infections, poor oral hygiene, adverse drug effects, deficiencies, aging, tobacco use, altered neurotransmitter levels
Neurotransmitters and Taste Threshold:
Effects of serotonin (5-HT) and norepinephrine (NE) on taste sensitivity
Supertasters:
25% of the population with heightened sensitivity to taste, especially bitterness
Increased number of fungiform papillae
The prostate is an exocrine gland of the male mammalian reproductive system
It is a walnut-sized gland that forms part of the male reproductive system and is located in front of the rectum and just below the urinary bladder
Function is to store and secrete a clear, slightly alkaline fluid that constitutes 10-30% of the volume of the seminal fluid that along with the spermatozoa, constitutes semen
A healthy human prostate measures (4cm-vertical, by 3cm-horizontal, 2cm ant-post ).
It surrounds the urethra just below the urinary bladder. It has anterior, median, posterior and two lateral lobes
It’s work is regulated by androgens which are responsible for male sex characteristics
Generalised disease of the prostate due to hormonal derangement which leads to non malignant enlargement of the gland (increase in the number of epithelial cells and stromal tissue)to cause compression of the urethra leading to symptoms (LUTS
- Video recording of this lecture in English language: https://youtu.be/lK81BzxMqdo
- Video recording of this lecture in Arabic language: https://youtu.be/Ve4P0COk9OI
- Link to download the book free: https://nephrotube.blogspot.com/p/nephrotube-nephrology-books.html
- Link to NephroTube website: www.NephroTube.com
- Link to NephroTube social media accounts: https://nephrotube.blogspot.com/p/join-nephrotube-on-social-media.html
Lung Cancer: Artificial Intelligence, Synergetics, Complex System Analysis, S...Oleg Kshivets
RESULTS: Overall life span (LS) was 2252.1±1742.5 days and cumulative 5-year survival (5YS) reached 73.2%, 10 years – 64.8%, 20 years – 42.5%. 513 LCP lived more than 5 years (LS=3124.6±1525.6 days), 148 LCP – more than 10 years (LS=5054.4±1504.1 days).199 LCP died because of LC (LS=562.7±374.5 days). 5YS of LCP after bi/lobectomies was significantly superior in comparison with LCP after pneumonectomies (78.1% vs.63.7%, P=0.00001 by log-rank test). AT significantly improved 5YS (66.3% vs. 34.8%) (P=0.00000 by log-rank test) only for LCP with N1-2. Cox modeling displayed that 5YS of LCP significantly depended on: phase transition (PT) early-invasive LC in terms of synergetics, PT N0—N12, cell ratio factors (ratio between cancer cells- CC and blood cells subpopulations), G1-3, histology, glucose, AT, blood cell circuit, prothrombin index, heparin tolerance, recalcification time (P=0.000-0.038). Neural networks, genetic algorithm selection and bootstrap simulation revealed relationships between 5YS and PT early-invasive LC (rank=1), PT N0—N12 (rank=2), thrombocytes/CC (3), erythrocytes/CC (4), eosinophils/CC (5), healthy cells/CC (6), lymphocytes/CC (7), segmented neutrophils/CC (8), stick neutrophils/CC (9), monocytes/CC (10); leucocytes/CC (11). Correct prediction of 5YS was 100% by neural networks computing (area under ROC curve=1.0; error=0.0).
CONCLUSIONS: 5YS of LCP after radical procedures significantly depended on: 1) PT early-invasive cancer; 2) PT N0--N12; 3) cell ratio factors; 4) blood cell circuit; 5) biochemical factors; 6) hemostasis system; 7) AT; 8) LC characteristics; 9) LC cell dynamics; 10) surgery type: lobectomy/pneumonectomy; 11) anthropometric data. Optimal diagnosis and treatment strategies for LC are: 1) screening and early detection of LC; 2) availability of experienced thoracic surgeons because of complexity of radical procedures; 3) aggressive en block surgery and adequate lymph node dissection for completeness; 4) precise prediction; 5) adjuvant chemoimmunoradiotherapy for LCP with unfavorable prognosis.
1. Dr. Vasant C Gosai
1
GENE REGULATION-
PROKARYOTICS
Prokaryotic cell. In a cell lacking a nucleus, mRNA
produced by transcription is immediately translated
without additional processing.
(a)
TRANSLATION
TRANSCRIPTION
DNA
mRNA
Ribosome
Polypeptide
2. INTRODUCTION
2
The fundamental problem of chemical physiology
and of embryology is to understand why tissue cells
do not all express, all the time, all the potentialities
inherent in their genome.
—François Jacob and Jacques Monod..
Of the 4,000 or so genes in the typical bacterial
genome, or the perhaps 1,00,000 genes in the
human genome, only a fraction are expressed in a
cell at any given time.
3. Significance of gene Expression
3
Regulated expression of genes is required for
Adaptation,
Differentiation and
Development
4. 1)ADAPTATION
4
Organisms adapt to environmental changes by
altering gene expression.
a) Bacteria are highly versatile and responsive
organisms: the rate of synthesis of some
proteins in bacteria may vary more than a 1000-
fold in response to the supply of nutrients or to
environmental challenges.
b) Cells of multicellular organisms also respond to
varying conditions.
c) Such cells exposed to hormones and growth
factors change substantially in shape, growth
rate, and other characteristics.
5. differentiation and
development
5
The genetic information present in each somatic
cell of a metazoan organism is practically
identical.
The exceptions in the genetic information are
found in those few cells that have amplified or
rearranged genes in order to perform specialized
cellular functions.
As the high cost of protein synthesis, regulation of
gene expression is essential to making optimal
use of the energy.
6. PRINCIPLE OF GENE
REGULATION
6
HOUSEKEEPING GENES: Genes for products
that are required at all times.
Ex : enzymes of Glycolysis are synthesised by all
cells .
CONSTITUTIVE GENE EXPRESSION
:Unvarying expression of a gene.
REGULATED GENE EXPRESSION: For other
gene products, cellular levels rise and fall in
response to molecular signals.
7. 7
INDUCTION : Induction is turning “on”
the switch of the gene.
A phenomena of increased synthesis of
protein or enzyme in response to certain
signal.
Such enzymes are said to be Inducible.
Signals are called Inducers.
8. 8
REPRESSION is turning “off” the gene
expression.
In prokaryotes,the genes involved in a
metabolic pathway are often present in a
linear array called an operon eg, the
lac operon.
An operon can be regulated by a single
promoter or regulatory region.
9. 9
CISTRON : The smallest unit of genetic
expression
The cistron is the genetic unit coding for protein
molecule.
A single mRNA that encodes more than one type
of translated protein is referred to as a
polycistronic mRNA.
10. 10
For example, the polycistronic lac operon mRNA
is translated into three separate proteins.
Operons and polycistronic mRNAs are common
in bacteria but not in eukaryotes
Transcription is mediated and regulated by
protein-DNA interactions, especially those
involving the protein components of RNA
polymerase.
12. RNA POLYMARASE BINDS TO DNA AT
PROMOTERS
12
Promoter site: near points at RNA synthesis begins.
RNA polymerases bind to DNA and initiate transcription at promoters.
TRANSCRIPTION INITIATION IS REGULATED BY PROTEIN THAT
BIND TO OR NEAR PROMOTER
At least three type of protein regulate transcription initiation by RNA
polymerase.
1.SPECIFICITY FACTORS: alter specificity of RNA polymerase for given
promoter or to the set of promoter.
e.g. the σ subunit of the E.coli RNA Polymerase
2.REPRESSORS : impede access of RNA Polymerase to the promoter
3.ACTIVATORS : enhance the RNA polymerase-promoter interaction.
13. 13
Repressors bind to specific sites on the DNA. These
sites, called OPERATORS, are generally near a
promoter.
RNA polymerase movement is blocked when the
repressor is present.
Regulation by repressor protein that blocks
transcription is NEGATIVE REGULATION.
14. 14
Types of Gene Expression
There are mainly two types of gene expression and regulation:
a. Positive regulation
b. Negative regulation.
a. Positive regulation:
• When the expression of genetic information is quantitatively increased by
the presence of specific regulatory element, it is called as positive regulation.
• The element or molecule mediating positive regulation is called positive
regulator.
• Ex : Lac Operon
b. Negative regulation:
•When the expression of genetic information is decreased by the presence of
a specific regulatory element, it is called as negative regulation.
•The element or molecule mediating the negative regulation is called a negative
regulator.
•Ex : Tryptophan Operon
15. REGULATION IN
PROKARYOTES
15
1. LAC OPERON
2. TRYPTOPHAN OPERON BY ATTENUATION
3. ARABINOSE OPERON
4. SOS RESPONSE
5. RIBOSOMAL PROTEIN SYNTHESIS
COORDINATED WITH rRNA SYNTHESIS
(STRINGENT RESPONSE)
6. REGULATION IN VIRUS ( LAMDA PHAGE)
16. LAC OPERON MODEL
16
Jacob and Monod in 1961 described their Operon
model in a classic paper.
Their hypothesis was to a large extent based on
observations on the regulation of lactose
metabolism by the intestinal bacterium E coli.
17. 17
Bacteria such as E. coli usually rely on glucose as
their source of carbon and energy.
When glucose is scarce, E. coli can use lactose as
their carbon source .
An essential enzyme in the metabolism of lactose is
β-galactosidase, which hydrolyzes lactose into
galactose and glucose.
19. 19
The lactose (lac) operon codes for three proteins involved
in the catabolism of the disaccharide, lactose :
I. lacZ gene codes for β-galactosidase, which hydrolyzes
lactose to galactose and glucose
II. The lacY gene, which codes for a permease that
facilitates the movement of lactose into the cell.
III. lacA gene that codes for thiogalactoside
transacetylase whose exact physiologic function is
unknown.
All of these proteins are produced when lactose is
available to cell.
The regulatory portion of the operon is upstream of the
three structural genes, and consists of the promoter (P)
region where RNA polymerase binds, and two additional
sites, the operator (O) site and the CAP site, where
regulatory proteins bind
20. 20
The lacZ, lacY, and lacA genes are expressed
only when the O site is empty.
The CAP site is bound by a complex of cyclic
adenosine monophosphate and the catabolite
gene activator protein or CAP.
A regulatory gene, the lacI gene, codes for the
repressor protein that binds to the operator site.
22. 22
When glucose is the only sugar available: In this
case, the lac operon is repressed (turned off).
Binding of the repressor interferes with the progress
of RNA polymerase, and blocks transcription of the
structural genes. This is an example of negative
regulation .
23. 23
When only lactose is available: In this case, the
lac operon is induced (expressed or turned on).
A small amount of lactose is converted to an
isomer, allolactose.
This compound is an inducer that binds to the
repressor protein, changing its conformation so
that it can no longer bind to the operator.
24. 24
In the absence of glucose, adenylyl cyclase is
active, and sufficient quantities of cAMP are
made and bind to the CAP protein.
The cAMP–CAP complex binds to the CAP-
binding site, causing RNA polymerase to more
efficiently initiate transcription at the promoter site
.
This is an example of positive regulation.
25. 25
When both glucose and lactose are available: In this
case, transcription of the lac operon is negligible,
even if lactose is present at a high concentration.
Adenylyl cyclase is deactivated in the presence of
glucose—a process known as catabolite
repression.
So no cAMP–CAP complex forms and the CAP-
binding site remains empty.
RNA polymerase is, therefore, unable to effectively
initiate transcription, even though the repressor may
not be bound to the operator region.
26. TRYPTOPHAN OPERON
26
The tryptophan (trp) operon codes for five
proteins that are required for the synthesis of the
amino acid, tryptophan.
This operon contains five structural genes:
trp E,
trp D,
trp C,
trp B, and
trp A, which encodes tryptophan synthetase.
27. 27
E- D codes for Anthranilate synthase I
C -Codes for N 5’ Antharanilate Isomease
(Indole 3- glycerol phophate synthetase)
B-Codes for Tryptophan syntheatse (Beta
subunit)
A –Codes for Tryptophan syntheatse (Alpha
subunit)
29. Organization of the trp operon and regulation via the trp
repressor protein
Cannot bind to
the operator site
RNA pol can bind to
the promoter
29
30. Organization of the trp operon and regulation via the trp
repressor protein30
31. 31
Negative control includes trp itself binding to the
repressor protein and facilitating the binding of the
repressor to the operator.
Repression by trp is not always complete, however,
the trp operon is also regulated by a process known
as attenuation.
With attenuation, transcription is initiated but is
terminated well before completion.
32. 32
If trp is plentiful, transcription initiation that
escaped repression by trp is attenuated (stopped)
by the formation at the 5′-end of the mRNA of a
hairpin (stem-loop) structure like that seen in ρ-
independent termination
Transcription and translation are coupled
processes in prokaryotes , therefore attenuation
also results in the formation of a truncated,
nonfunctional peptide product that is rapidly
degraded.
33. Sequence of the trpL mRNA produced during attenuation
These two codons provide a
way to sense if there is
sufficient tryptophan for
translation
The 3-4 stem loop
is followed by a
sequence of Uracils
Region 2 is complementary to regions 1 and 3
Region 3 is complementary to regions 2 and 4
Therefore several stem-loops structures are possible
It acts as an intrinsic
(r-independent)
terminator
33
36. 36
The lack of trp causes ribosomes to stall at these
codons, covering regions of the mRNA required
for formation of the attenuation hairpin.
This prevents attenuation and thus allows
transcription to continue.
37. ARABINOSE OPERON
37
The three structural genes (araB, araA, araD)
encode for enzymes needed for the metabolism
of the sugar arabinose in bacterial cells.
araB,araA, and araD encode for the enzymes
kinase, isomerase, and epimerase.
Isomerase converts arabinose to ribulose.
Kinase converts ribulose to ribulose-5-phosphate.
38. 38
The arabinose operon also contains the arabinose C
gene which produce Ara c protein
The araC gene regulates the expression of the
structural genes and the araC protein.
Thus, the araC gene is auto regulated.
The presence of both arabinose and the araC gene
product activates the expression of the BAD genes.
39. The araC gene is adjacent to the ara operon
It has its own promoter, PC
It encodes a regulatory protein, AraC
AraC can bind to three different operator sites
Designated araI, araO1 and araO2
The AraC protein can act as either a
negative or positive regulator of
transcription
Depending on whether or not
arabinose is present
39
40. POSITIVE REGULATION
40
When arabinose is present, it binds to AraC protein
and changes AraC conformation.
An arabinose- AraC dimer complex binds
preferentially to AraI and NOT to araO2 which
causes ‘opening ‘ of the loop.
This allows RNA pol to bind to PBAD.
If glucose levels are low, cAMP-CAP complex binds
to Pc & active the transcription
41. NEGATIVE REGULATION
41
When arabinose is absent, the AraC protein acts as
a negative regulator.
AraC acts as a dimer and causes the DNA loop.
Looping brings the AraI and araO2 sites in proximity
to one another.
One AraC monomer binds to araI and a second
monomer binds to araO2 .
Binding of araC prevents RNA pol from binding to
the PBAD promoter.
Transcription not occur.
43. INDUCTION OF SOS
RESPONSE
43
Extensive DNA damage in the bacterial chromosome
triggers the induction of many distantly located
genes.
This response, called the SOS response.
When DNA is extensively damaged(such as by UV
Iight)DNA replication is halted and the number of
single-strand in the DNA increases.
RecA protein binds to this damaged single-
stranded DNA activating the protein's co protease
activity.
45. 45
While bound to DNA, the RecA protein facilitates
cleavage and inactivation of the LexA repressor
when the repressor is inactivated the SOS genes
including recA, are induced;
RecA levels increase 50 to 100 fold.
46. RIBOSOMAL PROTEIN WITH
rRNA SYNTHESIS
46
Protein synthesis is major consumer of energy in
bacteria.
Because the number of ribosomes is primary
determinants of level of translation and ribosome
synthesis itself is an enrgy-intensive process.
When cells are in a condition where there is an
insufficient supply of amino acids to sustain
protein, the stringent response is activated.
47. STRINGENT RESPONSE
47
Stringent response causes a 10-20 times
reduction in the synthesis of rRNA and tRNA.
This causes a reduction of about 10% of the
mRNA in the cell.
The stringent response is accompanied by the
increase of the alarmones ppGpp and pppGpp:
guanosine tetraphosphate with diphosphates
attached to the 5’ and 3’ ends of guanosin.
Also guanosine pentaphosphate with a 5’
triphosphate group and 3’ diphosphate.
48. Charged tRNA binds to the A-site in riboso
Amino acid starvation results in an
uncharged
tRNA
-deacylated tRNA will bind to the A-site em
An uncharged tRNA is a signal for RelA
binding to the ribosome and synthesizes
ppGpp guanosine 3’5’ bisphophate, also
pppGpp
ppGpp now interacs with
RNA polymerase at key
metabolic pathways48
50. 50
The ppGpp molecule binds to the site where the
polymerase would form the open complex.
The mechanism of ppGpp then is to prevent the
open complex formation of the transcription.
51. REGULATORY MECHANISM IN
VIRUS
(TRANSDUCTION)
51
BACTERIOPHASE LAMDA:
some bacterial viruses can either reside in a
dormant state within the host chromosomes or
can replicate within the bacterium and eventually
lead to lysis and killing of the bacterial host.
When lambda infects an organism of that species
it injects its 45,000-bp, double-stranded, linear
DNA genome into the cell.
52. 52
Depending upon the nutritional state of the cell,
the lambda DNA will either integrate into the host
genome (lysogenic pathway) and remain
dormant until activated , or it will commence
replicating until it has made about 100 copies
of complete, protein-packaged virus, at which
point it causes lysis of its host (lytic pathway).
53. Virulent phages only
undergo a lytic cycle
Temperate phages can
follow both cycles
Prophage can
exist in a dormant
state for a long
time
It will undergo
the lytic cycle
This process is
termed
induction
53
54. 54
Inside the viral head, phage l DNA is linear.
After injection into the bacterium, the
two ends attach covalently to each other
forming a circle.
The organization of the genes within this circular
structure reflects the two alternative life cycles of
the virus.
55. 55
The genes on the left side of the viral
genome encode proteins that are
responsible for the lysogenic infection.
The genes on the right side of the viral
genome encode proteins that are
responsible for the lytic infection.
57. The OR Region Provides a Genetic
Switch Between the Two Cycles
57
The OR region contains three operator sites,
designated OR1, OR2, and OR3 .
These operator sites control two promoters, PR
and PRM, which transcribe in opposite directions.
The l repressor protein or the cro protein can
bind to any or all of the three operator sites.
This binding governs the switch between the
lysogenic and the lytic cycles.
58. l repressor has the
highest affinity to OR1
then OR2 then OR3
l repressor is a dimer
cooperative interaction
via
This binding inhibits
transcription from PR
So the lytic cycle is switched off
l repressor falls off
OR3 first
Cro protein has the
highest affinity to OR3
and simiar affinity to OR2
then OR1
cro protein is a dimer
This binding blocks transcription from PRM
So the lysogenic cycle is switched off
PR is not
needed in
the later
stages of
the lytic
cycle
58
61. Reference
61
Lehninger text book of biochemistry 5th edition
Harper,book of biochemistry,29th edition
Dinesh puri,text book of medical biochemistry,3rd
edition.
Google images.