cytochrome p450 is an super family of enzyme that contains a heme as co factor that function as monooxygenase. This enzyme has been identified in all kingdoms of life, like fungi, Protista, bacteria, and as well as in virus.
DOWNLOAD THE POWERPOINT FILE HERE:
https://www.dropbox.com/s/3izi11rbc7axri3/CHE-109.pptx?dl=0
A presentation slide on Peptides and Proteins. Presented in the Course CHE-109 in East West University.
Content :-
What is porphyrin?
Biosynthesis of porphyrin (heme)
Site
Reactions
Regulation
Degradation of heme
Site
Reactions
Reference
What is Porphyrin?
Porphyrins are cyclic compound formed by the linkage of four pyrrole rings through methyne(=HC-)bridges.
Structure of hemoglobin & chlorophyll
Examples of some important humanand animal hemoproteins.
Biosynthesis of heme
Site of biosynthesis:-
-Liver (hepatocyte) & Bone Marrow
( erythryoid producing cells )
2) ALA dehydratase :-
The substrates are two molecules of ALA.
The product is porphobilinogen, the first pyrrole.
ALA dehydratase is a -SH containing enzyme.
It is very susceptible to inhibition by lead.
3) Uroporphyrinogen I synthase and uroporphyrinogen IIIcosynthase
Production of uroporphyrinogen III requires two enzymes.The substrates are four molecules of porphobilinogen.
4) Uroporphyrinogen decarboxylase:-
Decarboxylates the acetic acid groups, converting them to methyl groups.
5) Coproporphyrinogen III oxidase:-
Catalyzes the conversion of two propionic acid groups to vinyl groups
6) Protoporphyrinogen IX oxidase:-
Protoporphyrinogen IX oxidase converts the methylene bridges between the pyrrole rings to methenyl bridges.
7) Ferrochelatase:-
Ferrochelatase adds Fe++ to protoporphyrin IX, forming heme.
• The enzyme requires Fe++, ascorbic acid and cysteine (reducing agents).
• Ferrochelatase is inhibited by lead.
Regulation of heme synthesis
Feedback regulation:- heme is a feedback inhibitor of ALA synthase. ALA synthase occurs in both hepatic (ALAS 1) and erythroid (ALAS 2) forms.
Effects of drugs and steroids:- Certain drugs and steroids can increase heme synthesis via increased production of the ratelimiting enzyme, ALA synthase
Substrate availability:- Fe++ must be available for ferrochelatase.
Degradation of heme
Site of Degradation :-
- cells of the reticulo endothelial system in spleen, liver and bone marrow
Heme Degradation
Most of the heme which is degraded comes from hemoglobin in red blood cells, which have a life span of about 120 days.
There is thus a turnover of about 6 g/day of hemoglobin.
Normally , senescent red blood cells and heme from other sources are engulfed by cells of the reticuloendothelial system.
The globin is recycled or converted into amino acids, which in turn are recycled or catabolized as required.
Heme is oxidized.
Microsomal heme oxygenase system
Transport of bilirubin in Plasma
Bilirubin on release from macrophages circulates as unconjugated bilirubin in plasma tightly bound to albumin.
HARPER’S ILLUSTRATED BIOCHEMISTRY (28TH EDITION) by robert murray,david A.bender,peter j kennekky,victor w rodwell,p.antony weil.(page No-271)
Biochemistry Lippincott’s Illustrated Reviews by Richard Harvey& Denise Ferrier
Macromolecules of life (Nucleic acids & Proteins)Amany Elsayed
Macromolecules of life (Nucleic acids & Proteins)
The Fibrous Proteins
The Collagens
The Globular Proteins
Structure and Function of Myoglobin
Minor Hemoglobin’s
Biological value of proteins
Nitrogen Balance
Protein Deficiency
This chapter will cover the important aspects related to the Biotransformation. it is a brief summary and concise form for students. if there is any mistake, please help me to correct it.
Thanks
Amjad Anwar Pharmacist
DOWNLOAD THE POWERPOINT FILE HERE:
https://www.dropbox.com/s/3izi11rbc7axri3/CHE-109.pptx?dl=0
A presentation slide on Peptides and Proteins. Presented in the Course CHE-109 in East West University.
Content :-
What is porphyrin?
Biosynthesis of porphyrin (heme)
Site
Reactions
Regulation
Degradation of heme
Site
Reactions
Reference
What is Porphyrin?
Porphyrins are cyclic compound formed by the linkage of four pyrrole rings through methyne(=HC-)bridges.
Structure of hemoglobin & chlorophyll
Examples of some important humanand animal hemoproteins.
Biosynthesis of heme
Site of biosynthesis:-
-Liver (hepatocyte) & Bone Marrow
( erythryoid producing cells )
2) ALA dehydratase :-
The substrates are two molecules of ALA.
The product is porphobilinogen, the first pyrrole.
ALA dehydratase is a -SH containing enzyme.
It is very susceptible to inhibition by lead.
3) Uroporphyrinogen I synthase and uroporphyrinogen IIIcosynthase
Production of uroporphyrinogen III requires two enzymes.The substrates are four molecules of porphobilinogen.
4) Uroporphyrinogen decarboxylase:-
Decarboxylates the acetic acid groups, converting them to methyl groups.
5) Coproporphyrinogen III oxidase:-
Catalyzes the conversion of two propionic acid groups to vinyl groups
6) Protoporphyrinogen IX oxidase:-
Protoporphyrinogen IX oxidase converts the methylene bridges between the pyrrole rings to methenyl bridges.
7) Ferrochelatase:-
Ferrochelatase adds Fe++ to protoporphyrin IX, forming heme.
• The enzyme requires Fe++, ascorbic acid and cysteine (reducing agents).
• Ferrochelatase is inhibited by lead.
Regulation of heme synthesis
Feedback regulation:- heme is a feedback inhibitor of ALA synthase. ALA synthase occurs in both hepatic (ALAS 1) and erythroid (ALAS 2) forms.
Effects of drugs and steroids:- Certain drugs and steroids can increase heme synthesis via increased production of the ratelimiting enzyme, ALA synthase
Substrate availability:- Fe++ must be available for ferrochelatase.
Degradation of heme
Site of Degradation :-
- cells of the reticulo endothelial system in spleen, liver and bone marrow
Heme Degradation
Most of the heme which is degraded comes from hemoglobin in red blood cells, which have a life span of about 120 days.
There is thus a turnover of about 6 g/day of hemoglobin.
Normally , senescent red blood cells and heme from other sources are engulfed by cells of the reticuloendothelial system.
The globin is recycled or converted into amino acids, which in turn are recycled or catabolized as required.
Heme is oxidized.
Microsomal heme oxygenase system
Transport of bilirubin in Plasma
Bilirubin on release from macrophages circulates as unconjugated bilirubin in plasma tightly bound to albumin.
HARPER’S ILLUSTRATED BIOCHEMISTRY (28TH EDITION) by robert murray,david A.bender,peter j kennekky,victor w rodwell,p.antony weil.(page No-271)
Biochemistry Lippincott’s Illustrated Reviews by Richard Harvey& Denise Ferrier
Macromolecules of life (Nucleic acids & Proteins)Amany Elsayed
Macromolecules of life (Nucleic acids & Proteins)
The Fibrous Proteins
The Collagens
The Globular Proteins
Structure and Function of Myoglobin
Minor Hemoglobin’s
Biological value of proteins
Nitrogen Balance
Protein Deficiency
This chapter will cover the important aspects related to the Biotransformation. it is a brief summary and concise form for students. if there is any mistake, please help me to correct it.
Thanks
Amjad Anwar Pharmacist
Pharmacokinetics involves absorption, distribution, metabolism and excretion. Metabolism involves a huge range of chemical reactions which occur at body temperature with the help of enzymes
metabolism of xenobiotis, drugs, medicine, carcinogen generation by enzymes like cyt p450 mono oxigenases, prostaglandin synthase ect. alcohol metabolism, toxin metabolism, definition of genobiotics, biotransformation, detoxification. effects on health
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
Couples presenting to the infertility clinic- Do they really have infertility...Sujoy Dasgupta
Dr Sujoy Dasgupta presented the study on "Couples presenting to the infertility clinic- Do they really have infertility? – The unexplored stories of non-consummation" in the 13th Congress of the Asia Pacific Initiative on Reproduction (ASPIRE 2024) at Manila on 24 May, 2024.
Knee anatomy and clinical tests 2024.pdfvimalpl1234
This includes all relevant anatomy and clinical tests compiled from standard textbooks, Campbell,netter etc..It is comprehensive and best suited for orthopaedicians and orthopaedic residents.
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!
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
263778731218 Abortion Clinic /Pills In Harare ,sisternakatoto
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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
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
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Ve...kevinkariuki227
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Ve...
Cytochrome p450
1. Cytochrome p450
Sandeep Jana
Department of Bachelor of Pharmaceutical Technology (3nd year)
BCDA College of Pharmacy & Technology, Hridaypur, 24 parganas (N), West
Bengal, India
Abstract:
Cytochromes P450 (CYPs) are a superfamily of enzymes containing heme as a cofactor that
function as monooxygenases. CYP enzymes have been identified in all kingdoms of
life: animals, plants, fungi, protista, bacteria, and as well as in viruses. More than 50,000
distinct CYP proteins are known. In mammals, these proteins oxidize steroids, fatty acids,
and xenobiotics, and are important for the clearance of various compounds, as well as for
hormone synthesis and breakdown. In plants, these proteins are important for the biosynthesis
of defensive compounds, fatty acids, and hormones.
Key words: cytochrome P450, cofactor, monooxygenases etc.
Introduction:
Cytochromes P450 (CYPs) are a superfamily of enzymes containing heme as a cofactor that
function as monooxygenases. In mammals, these proteins oxidize steroids, fatty acids,
and xenobiotics, and are important for the clearance of various compounds, as well as for
hormone synthesis and breakdown. In plants, these proteins are important for the biosynthesis
of defensive compounds, fatty acids, and hormones.
CYP enzymes have been identified in all kingdoms of life
animals, plants, fungi, protists, bacteria, and archaea, as well as in viruses. More than 50,000
distinct CYP proteins are known.
CYPs are, in general, the terminal oxidase enzymes in electron transfer chains, broadly
categorized as P450-containing systems. The term "P450" is derived from
the spectrophotometric peak at the wavelength of the absorption maximum of the enzyme
(450 nm) when it is in the reduced state and complexed with carbon monoxide. Most CYPs
require a protein partner to deliver one or more electrons to reduce the iron (and eventually
molecular oxygen).
Classification: Based on the nature of the electron transfer proteins, CYPs can be classified
into several groups
• Microsomal P450 systems
In which electrons are transferred from NADPH via cytochrome P450
reductase (variously CPR, POR, or CYPOR). Cytochrome b5 (cyb5) can also
contribute reducing power to this system after being reduced by cytochrome
b5 reductase (CYB5R).
2. • Mitochondrial P450 systems
Which employ adrenodoxin reductase and adrenodoxin to transfer electrons from
NADPH to P450.
• Bacterial P450 systems
Which employ a ferredoxin reductase and a ferredoxin to transfer electrons to P450.
Catalytic cycle:
1. Substrate binds in proximity to the heme group, on the side opposite to the axial
thiolate. Substrate binding induces a change in the conformation of the active site,
often displacing a water molecule from the distal axial coordination position of the
heme iron, and changing the state of the heme iron from low-spin to high-spin.
2. Substrate binding induces electron transfer from NAD(P)H via cytochrome P450
reductase or another associated reductase.
3. Molecular oxygen binds to the resulting ferrous heme center at the distal axial
coordination position, initially giving a dioxygen adduct not unlike oxy-myoglobin.
4. A second electron is transferred, from either cytochrome P450 reductase, ferredoxins,
or cytochrome b5, reducing the Fe-O2 adduct to give a short-lived peroxo state.
5. The peroxo group formed in step 4 is rapidly protonated twice, releasing one molecule
of water and forming the highly reactive species referred to as P450 Compound 1 (or
just Compound I). This highly reactive intermediate was isolated in 2010, P450
Compound 1 is an iron(IV) oxo (or ferryl) species with an additional oxidizing
equivalent delocalized over the porphyrin and thiolate ligands. Evidence for the
alternative perferryl iron(V)-oxo is lacking.
6. Depending on the substrate and enzyme involved, P450 enzymes can catalyze any of
a wide variety of reactions. A hypothetical hydroxylation is shown in this illustration.
After the product has been released from the active site, the enzyme returns to its
original state, with a water molecule returning to occupy the distal coordination
position of the iron nucleus.
Cytochrome P450 in Human:
Human CYPs are primarily membrane-associated proteins located either in the inner
membrane of mitochondria or in the endoplasmic reticulum of cells. CYPs metabolize
thousands of endogenous and exogenous chemicals. Some CYPs metabolize only one (or a
very few) substrates, such as CYP19 (aromatase), while others may metabolize
multiple substrates. Both of these characteristics account for their central importance
in medicine. Cytochrome P450 enzymes are present in most tissues of the body, and play
important roles in hormone synthesis and breakdown
(including estrogen and testosterone synthesis and metabolism), cholesterol synthesis,
and vitamin D metabolism. Cytochrome P450 enzymes also function to metabolize
potentially toxic compounds, including drugs and products of endogenous metabolism such
as bilirubin, principally in the liver.
3. Drug metabolism
CYPs are the major enzymes involved in drug metabolism, accounting for about 75% of the
total metabolism. Most drugs undergo deactivation by CYPs, either directly or by
facilitated excretion from the body. Also, many substances are bio-activated by CYPs to form
their active compounds like the antiplatelet drug clopidogrel.
Drug interaction
Many drugs may increase or decrease the activity of various CYP isozymes either by
inducing the biosynthesis of an isozyme (enzyme induction) or by directly inhibiting the
activity of the CYP (enzyme inhibition). A classical example includes anti-epileptic drugs,
such as Phenytoin, which induces CYP1A2, CYP2C9, CYP2C19, and CYP3A4.
Many substrates for CYP3A4 are drugs with a narrow therapeutic index, such as amiodarone
or carbamazepine. Because these drugs are metabolized by CYP3A4, the mean plasma
levels of these drugs may increase because of enzyme inhibition or decrease because of
enzyme induction.
Conclusion
CYP is a complex and important component of drug metabolism. It is the root of many drug
interactions due to inhibition, induction, and competition for common enzymatic pathways by
different drugs. Genetic variability of CYP is also a significant source of unpredictable drug
effects. Awareness and understanding of drugs involved in common CYP pathways will help
to prevent potential drug interactions and untoward effects.