The document summarizes dihydrofolate reductase (DHFR) enzyme. DHFR catalyzes the reduction of dihydrofolate to tetrahydrofolate using NADPH as a cofactor. It is found in both prokaryotic and eukaryotic cells and is essential for purine and thymidylate synthesis required for cell growth. The structure of DHFR contains beta sheets and alpha helices that form two subdomains containing the active site. Several inhibitors target DHFR including trimethoprim, methotrexate, and pyrimethamine. These inhibitors mimic the structure of dihydrofolate and bind tightly in the active site to inhibit the enzyme.
MOLECULAR DOCKING AND DRUG RECEPTOR INTERACTION AGENT ACTING.pptxMO.SHAHANAWAZ
Point to point M.pharm CADD presentation on MOLECULAR DOCKING AND DRUG RECEPTOR INTERACTION AGENT ACTING, Dihydro Folate reductase Inhibiter (Methotrexate)
CHEMISTRY OF PEPTIDES [M.PHARM, M.SC, BSC, B.PHARM]Shikha Popali
THE CHEMISTRY OF PEPTIDES THE DIFFICULT TO COLLECT DATA FOR READERS , THREFORE HERE WE HAVE COLLECTED ALL THE DATA AT A PLACE AND PROVIDED EASIER TO CHEMISTRIANS.
This Powerpoint describes what is Flow chemistry, what are its advantages over batch method, Continuous flow reactor and Applications of Continuous flow chemistry.
SIDE REACTION OCCUR IN PEPTIDE YNTJESIS ARE DISCUSSED HERE WITH ITTATED PROTON, PROTONATIONS RACEMIZATION, INITIATED ACTIVITY, ACYLATION, ALKYLATION, OVERACTIVATION
What is QSAR?, introduction to 3D QSAR, CoMFA, CoMSIA, Case Study on CoMFA contour maps analysis and CoMSIA interactive forces between ligand and receptor, various Statistical techniques involved in QSAR
MOLECULAR DOCKING AND DRUG RECEPTOR INTERACTION AGENT ACTING.pptxMO.SHAHANAWAZ
Point to point M.pharm CADD presentation on MOLECULAR DOCKING AND DRUG RECEPTOR INTERACTION AGENT ACTING, Dihydro Folate reductase Inhibiter (Methotrexate)
CHEMISTRY OF PEPTIDES [M.PHARM, M.SC, BSC, B.PHARM]Shikha Popali
THE CHEMISTRY OF PEPTIDES THE DIFFICULT TO COLLECT DATA FOR READERS , THREFORE HERE WE HAVE COLLECTED ALL THE DATA AT A PLACE AND PROVIDED EASIER TO CHEMISTRIANS.
This Powerpoint describes what is Flow chemistry, what are its advantages over batch method, Continuous flow reactor and Applications of Continuous flow chemistry.
SIDE REACTION OCCUR IN PEPTIDE YNTJESIS ARE DISCUSSED HERE WITH ITTATED PROTON, PROTONATIONS RACEMIZATION, INITIATED ACTIVITY, ACYLATION, ALKYLATION, OVERACTIVATION
What is QSAR?, introduction to 3D QSAR, CoMFA, CoMSIA, Case Study on CoMFA contour maps analysis and CoMSIA interactive forces between ligand and receptor, various Statistical techniques involved in QSAR
Stages of scale up process mparm 1st year pharmaceutical process chemistryDhanashreeSarwan
Define Scale up process, need of Scale up technique, Stages of scale up process Bench\lab scale, pilot plant, large scale up technique, validation of large scale up process
Process chemistry AS PER PCI SYLLABUS FOR M.PHARMShikha Popali
pharmaceutical process chemistry is process WHERE FROM THE RESEARCH TO FINISH PRODUCT INCLUDING THE PRODUCT DEVELOPMENT AT LABORATORY LEVEL THAN PILOT PLANT WHERE THE PRODUCT IS MANUFACTURED IN 10X THAN FINAL AT 100X THAT IS SCALE UP PLANT.
Stages of scale up process mparm 1st year pharmaceutical process chemistryDhanashreeSarwan
Define Scale up process, need of Scale up technique, Stages of scale up process Bench\lab scale, pilot plant, large scale up technique, validation of large scale up process
Process chemistry AS PER PCI SYLLABUS FOR M.PHARMShikha Popali
pharmaceutical process chemistry is process WHERE FROM THE RESEARCH TO FINISH PRODUCT INCLUDING THE PRODUCT DEVELOPMENT AT LABORATORY LEVEL THAN PILOT PLANT WHERE THE PRODUCT IS MANUFACTURED IN 10X THAN FINAL AT 100X THAT IS SCALE UP PLANT.
Metabolism of 5-FU, deoxyuridine, and dUTP in Brain Mitochondria:kathleenmccann
5-FU (5-flourouracil) is currently in clinical trials for treatment of gliomas.1 In neoplastic cells, this drug is metabolized by two pathways. 5-FU is converted to
5-dUMP by thymidine phosphorylase and thymidine kinase. 5-FdUMP then competitively inhibits the conversion of dUMP to TMP by thymidylate synthase. This increases dUTP and depletes the TTP needed for DNA synthesis and repair, leading to apoptosis. 5-FdUMP is further phosphorylated to 5-FdUTP and is incorporated into DNA. In the second pathway, 5-FU is phosphorylated by actions of uridine phosphorylase and uridine kinase to 5-FUMP and then further phosphorylated to 5-FUTP and incorporated into RNA. However, the metabolism of 5-FU is as yet undefined in brain. 5-FU neurotoxicity may present as leukoencephalopathy, cerebellar signs, or acute demyelination. The use of thymidine infusions to reverse symptoms strongly suggested that the neurotoxicity is caused by dNTP pool imbalance. It is necessary to understand the underlying mechanisms to minimize neurotoxicity and judiciously use therapeutic thymidine.
Deoxyuridine metabolism in the brain mitochondria is not fully understood. While a small amount is needed for RNA synthesis, incorporation of dUTP into mitochondrial DNA (mtDNA) can lead to mutagenesis and apoptosis, especially as base excision repair is known to be inefficient in brain mtDNA.
These investigations aim to establish the activity of the enzymes necessary for regulation of dUTP pools in brain mitochondria: dUTPase, thymidine phosphorylase, and thymidine synthase. We also investigate the metabolism of 5-flourouricil (5-FU), the metabolite of which, 5-FdUMP, functions as a dUMP analogue.
Photophosphorylation/Photosynthesis/Light reactionM. Adnan Qadar
This ppt contain an easy understanding guide for teachers and students. All the contents are reviewed and edited by senior professors.
References
1. Taiz & Zeiger
2. Salisbury author
This ppt contain an easy understanding guide for teachers and students. All the contents are reviewed and edited by senior professors. This ppt contain an easy understanding guide for teachers and students. All the contents are reviewed and edited by senior professors. This ppt contain an easy understanding guide for teachers and students. All the contents are reviewed and edited by senior professors. This ppt contain an easy understanding guide for teachers and students. All the contents are reviewed and edited by senior professors. This ppt contain an easy understanding guide for teachers and students. All the contents are reviewed and edited by senior professors. This ppt contain an easy understanding guide for teachers and students. All the contents are reviewed and edited by senior professors. This ppt contain an easy understanding guide for teachers and students. All the contents are reviewed and edited by senior professors. This ppt contain an easy understanding guide for teachers and students. All the contents are reviewed and edited by senior professors. This ppt contain an easy understanding guide for teachers and students. All the contents are reviewed and edited by senior professors. This ppt contain an easy understanding guide for teachers and students. All the contents are reviewed and edited by senior professors. This ppt contain an easy understanding guide for teachers and students. All the contents are reviewed and edited by senior professors. This ppt contain an easy understanding guide for teachers and students. All the contents are reviewed and edited by senior professors. This ppt contain an easy understanding guide for teachers and students. All the contents are reviewed and edited by senior professors. This ppt contain an easy understanding guide for teachers and students. All the contents are reviewed and edited by senior professors. This ppt contain an easy understanding guide for teachers and students. All the contents are reviewed and edited by senior professors. This ppt contain an easy understanding guide for teachers and students. All the contents are reviewed and edited by senior professors. This ppt contain an easy understanding guide for teachers and students. All the contents are reviewed and edited by senior professors. This ppt contain an easy understanding guide for teachers and students. All the contents are reviewed and edited by senior professors.
The all the content in this profile is completed by the teachers, students as well as other health care peoples.
thank you, all the respected peoples, for giving the information to complete this presentation.
this information is free to use by anyone.
N-terminal tails of histones are the most accessible regions for modifications. These post-translational modification (PTM) of histones is a crucial step in epigenetic regulation of a gene.
What are terpenes ?
Terpenes are secondary metabolites which are produced by Plants for their defense mechanism or required as per their metabolism. They are unsaturated and conjugated compounds may be aromatic or alliphatic
Flu Vaccine Alert in Bangalore Karnatakaaddon Scans
As flu season approaches, health officials in Bangalore, Karnataka, are urging residents to get their flu vaccinations. The seasonal flu, while common, can lead to severe health complications, particularly for vulnerable populations such as young children, the elderly, and those with underlying health conditions.
Dr. Vidisha Kumari, a leading epidemiologist in Bangalore, emphasizes the importance of getting vaccinated. "The flu vaccine is our best defense against the influenza virus. It not only protects individuals but also helps prevent the spread of the virus in our communities," he says.
This year, the flu season is expected to coincide with a potential increase in other respiratory illnesses. The Karnataka Health Department has launched an awareness campaign highlighting the significance of flu vaccinations. They have set up multiple vaccination centers across Bangalore, making it convenient for residents to receive their shots.
To encourage widespread vaccination, the government is also collaborating with local schools, workplaces, and community centers to facilitate vaccination drives. Special attention is being given to ensuring that the vaccine is accessible to all, including marginalized communities who may have limited access to healthcare.
Residents are reminded that the flu vaccine is safe and effective. Common side effects are mild and may include soreness at the injection site, mild fever, or muscle aches. These side effects are generally short-lived and far less severe than the flu itself.
Healthcare providers are also stressing the importance of continuing COVID-19 precautions. Wearing masks, practicing good hand hygiene, and maintaining social distancing are still crucial, especially in crowded places.
Protect yourself and your loved ones by getting vaccinated. Together, we can help keep Bangalore healthy and safe this flu season. For more information on vaccination centers and schedules, residents can visit the Karnataka Health Department’s official website or follow their social media pages.
Stay informed, stay safe, and get your flu shot today!
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
New Drug Discovery and Development .....NEHA GUPTA
The "New Drug Discovery and Development" process involves the identification, design, testing, and manufacturing of novel pharmaceutical compounds with the aim of introducing new and improved treatments for various medical conditions. This comprehensive endeavor encompasses various stages, including target identification, preclinical studies, clinical trials, regulatory approval, and post-market surveillance. It involves multidisciplinary collaboration among scientists, researchers, clinicians, regulatory experts, and pharmaceutical companies to bring innovative therapies to market and address unmet medical needs.
Ozempic: Preoperative Management of Patients on GLP-1 Receptor Agonists Saeid Safari
Preoperative Management of Patients on GLP-1 Receptor Agonists like Ozempic and Semiglutide
ASA GUIDELINE
NYSORA Guideline
2 Case Reports of Gastric Ultrasound
- 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
Acute scrotum is a general term referring to an emergency condition affecting the contents or the wall of the scrotum.
There are a number of conditions that present acutely, predominantly with pain and/or swelling
A careful and detailed history and examination, and in some cases, investigations allow differentiation between these diagnoses. A prompt diagnosis is essential as the patient may require urgent surgical intervention
Testicular torsion refers to twisting of the spermatic cord, causing ischaemia of the testicle.
Testicular torsion results from inadequate fixation of the testis to the tunica vaginalis producing ischemia from reduced arterial inflow and venous outflow obstruction.
The prevalence of testicular torsion in adult patients hospitalized with acute scrotal pain is approximately 25 to 50 percent
These lecture slides, by Dr Sidra Arshad, offer a quick overview of physiological basis of a normal electrocardiogram.
Learning objectives:
1. Define an electrocardiogram (ECG) and electrocardiography
2. Describe how dipoles generated by the heart produce the waveforms of the ECG
3. Describe the components of a normal electrocardiogram of a typical bipolar leads (limb II)
4. Differentiate between intervals and segments
5. Enlist some common indications for obtaining an ECG
Study Resources:
1. Chapter 11, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 9, Human Physiology - From Cells to Systems, Lauralee Sherwood, 9th edition
3. Chapter 29, Ganong’s Review of Medical Physiology, 26th edition
4. Electrocardiogram, StatPearls - https://www.ncbi.nlm.nih.gov/books/NBK549803/
5. ECG in Medical Practice by ABM Abdullah, 4th edition
6. ECG Basics, http://www.nataliescasebook.com/tag/e-c-g-basics
These simplified slides by Dr. Sidra Arshad present an overview of the non-respiratory functions of the respiratory tract.
Learning objectives:
1. Enlist the non-respiratory functions of the respiratory tract
2. Briefly explain how these functions are carried out
3. Discuss the significance of dead space
4. Differentiate between minute ventilation and alveolar ventilation
5. Describe the cough and sneeze reflexes
Study Resources:
1. Chapter 39, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 34, Ganong’s Review of Medical Physiology, 26th edition
3. Chapter 17, Human Physiology by Lauralee Sherwood, 9th edition
4. Non-respiratory functions of the lungs https://academic.oup.com/bjaed/article/13/3/98/278874
Explore natural remedies for syphilis treatment in Singapore. Discover alternative therapies, herbal remedies, and lifestyle changes that may complement conventional treatments. Learn about holistic approaches to managing syphilis symptoms and supporting overall health.
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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
2. DIHYDROFOLATE REDUCTASE (DHFR)
• It is the reductase enzyme which catalyzes the
reduction of 7,8 Dihydrofolate through a
stereospecific hydride transfer from
NADPH(reduced form)cofactor to produced
5,6,7,8 Tetrahydrofolate product.
• It is found ubiquitously in all dividing cells of
prokaryotes and eukaryotes.
• MECHANISM OF ACTION:
• Tetrahydrofolate(FH4),which is produced from
the vitamin folate (B9) is primary one carbon
carrier in the body .
• While one carbons units are attached to FH4 at
N5 OR N10 Or form bridge between N5 and
N10 by donation of amino acids (majorly serine),
(histidine etc.) they can be oxidized or reduced
depends upon the requirement by biochemical
reaction .
3. • One of the major acceptor of this is deoxy-
uridine monophosphate which accepts
N5,N10 –methylene from FH4 to yield deoxy -
thymidine monophosphate(dTMP), purine
precursor.
• This is essential for purine and thymidylate
synthesis ,which are important for cell growth
and cell proliferation .
DHFR STRUCTURE:
• It is a cytosolic protein(186 amino
acids) of 21.3 kDa and uses NADPH
as cofactor.
• The DHFR sequence in humans
is 30% similar to that of E.coli and
70% similar to Other mammalian.
DHFR.
• The standard source of this enzyme is mammalian and
avian liver.
• In humans this enzyme is encoded by DHFR gene . It is
found in the q11-q22 region of chromosome 5.
• Four alpha helix connects successive beta strands.
• A central eight standard beta-pleated sheet makes up
the main feature of the polypeptide backbone folding of
DHFR.
.
4. • Seven of these strands are parallel and the eighth is antiparallel.
• The protein is divided into two subdomains , the adenosine
binding sub – domain and the loop domain .
• The adenosine binding sub -domain is larger of two and binds
adenoside moiety of NADPH .
• The loop subdomains consist of three loops, the Met-20 loop, the
F-G (phenylalanine –glycine) loop, and the G-H (glycine –
histidine)loop.
• Between these two loops there is active site .
• The active site is situated in N-terminal half of the sequence,which
includes a conserved Pro-trp dipeptide; the tryptophan has been
shown to be involved in the binding of substrate by the enzyme.
• The size of the active site is regulated by movements of the two
subdomains.
• E.COLI (ESCHERICHIA COLI) dihydrofolate reductase is an
important target of antibacterial medications .
• E.coli DHFR is small (18kb) protein with an α/ ꞵ structure consist
of a central eight stranded ꞵ -sheet and four flanking α-helices.
• The active site cleft of divides the protein into two structural
domains: 1).adenosine binding subdomain (light blue) and 2.)the
major subdomain : MET20(green),dark blue(F-G),and red (G-
H).
• The ternary complex of folate and NADP + illustrates the substrate
and cofactor binding site .
5. • There are five hydrogen bonds between folate
and DHFR active site :
1) Two H-bonds between ARG 70 and folate (
carboxylate group of glutamate )
2) Two H-bonds between GLU 30 and folate( NH2
and NH moiety of pyrimidine ring of pteridine ring)
• The GLU 30 is responsible for the protonation of
substrate and holds the substrate during the
catalytic activity of enzyme.
3) the other residues which interact with the folate
are:
1) One H- bond between ASN 64 and folate( C=O
of p-amino benzoic acid)
2) PHE 34 (through pi –pi interaction ) with folate (
phenyl ring of p-amino benzoic acid
FOLLOWING PICTURE
ILLUSTRATES HOW THE
COMPLEX OF DHFR AND
FOLATE FORM :
6. LIST OF VARIOUS INHIBITORS ACT ON THIS DHFR
ENZYME :
1. TRIMETHOPRIM –BLOCKS BACTERIAL
ENZYME
2. PYRIMETHAMINE ---PROTOZOAL
ENZYME
3. METHOTRAXATE ---MAMMALIAN
ENZYME
1.TRIMETHOPRIM : 5-(3,4,5-
TRIMETHOXYBENZYL) -2,4-PYRIMIDINE
-DIAMINE is a anti – bacterial drug used to treat
various infections like urinary tract infections,
respiratory tract infections and g.i.t. tract
infections.
• It is 50,000 TIMES more active against bacterial
DHFR enzyme than mammalian DHFR so, no
harm to human folate metabolism .
• It is used with sulphamethoxazole due to their
complementarity and synergistic action together
to achieve bactericidal action .
7. • 1.FIG. DEPICTING THE INTERACTION OF
TRIMETHOPRIM WITH THE DHFR AND
NADPH( DHRF OF LACTOBACILLUS CASEI)
• 2. FIG. : H-BOND
• INTERACTION B/W
• DHFR OF E.COLI
• AND TRIMETHOPRIM
• LIKE THE NATURAL SUBSTRATE , TRIMETHOPRIM
BINDS TO THE ENZYME ALONG THE NADPH IN A
TERNARY COMPLEX, IN WHICH THE REDUCING END
OF THE CO-FACTOR IS SITED NEAR TO PYRIMIDINE
RING OF TRIMETHOPRIM .
• TRIMETHOPRIM ,METHOTRAXATE ,PYRIMETHAMINE
HAVE 2,4-AMINOPYRIMIDINE RING WHICH
RESEMBLES THE PTERIDINE NUCLEUS OF
DIHYDROFOLATE.
• BY NMR AND X-RAY IT IS FOUND THAT N1 OF
TRIMETHOPRIM IS PROTONATED IN BOUND STATE .
• AND X-RAY CRYSTALLOGRAPHYALSO SHOWS THAT
TRIMETHOPRIM LOCATE IN A DEEP CLEFT OF THE
PROTEIN , WITH FAVOURABLE NON-COVALENT
INTERACTIONS HELPING TO MAINTAIN ITS POSSITION
.
• THIS BINDING MODE ENABLES IONIC INTERACTIONS
BETWEEN THE PROTONATED N1 AND CARBOXYLATE
GROUP OF THE CONSERVED AMINO ACID RESIDUE,
AND HYDROGEN BONDING INTERATIONS AS SHOWN
IN THE PICTURE.
• THESE COMPLEX INTERACTIONS HOLDING THE
TRIMETHOPRIM AND DHFR TOGETHER , RESULTS IN
POTENT INHIBITORY EFFECT OF TRIMETHOPRIM UPON
BACTERIAL DHFR.
8. METHOTRAXATE :
• IT is a dihydrofolate reductase
inhibitor that is used in the
treatment of autoimmune
inflammatory disease such as
rheumatid arithritis and also as a
antineoplastic drug .
10. Pyrimethamine :
• It is a directly acting inhibitor of plasdmodial
DHFRase.
• It gradually reduces the schizogony of
malarial parasite in blood .
• It is slowly acting erythrocytic schizontocide.
• STRUCTURE:
Moa:
Interactions between DHFR and Pyrimethamine: