Nucleotide metabolism (purine and pyrimidine synthesis)Areeba Ghayas
NUCLEOTIDE METABOLISM,DE NOVO SYNTHESIS OF PURINE, SALVAGE PATHWAY OF PURINE, DE-NOVO SYNTHESIS OF PYRIMIDINE, SALVAGE PATHWAY OF PYRIMIDINE, GOUT, HYPERURICEMIA, LESCH-NYAN SYNDROME, OROTIC ACIDURIA
introduction of Purine and Pyrimidine metabolism, biosynthesis and degradation of nucleotides, biological functions and metabolic disorders, chemical analogues and therapeutic drugs, uric acid metabolism
Metabolism of amino acids (general metabolism)Ashok Katta
Metabolism of amino acids (general metabolism).
Part - I of amino acid metabolism.
This presentation covers Transamination, deamination, formation and Transport of Ammoniaand etc.
De novo synthesis of fatty acids (Biosynthesis of fatty acids)Ashok Katta
Synthesis of fatty acids in the body. Detailed pathway for de novo synthesis of fatty acids in the body including its energetic and regulation. also cover Multienzyme complex
Nucleotide metabolism (purine and pyrimidine synthesis)Areeba Ghayas
NUCLEOTIDE METABOLISM,DE NOVO SYNTHESIS OF PURINE, SALVAGE PATHWAY OF PURINE, DE-NOVO SYNTHESIS OF PYRIMIDINE, SALVAGE PATHWAY OF PYRIMIDINE, GOUT, HYPERURICEMIA, LESCH-NYAN SYNDROME, OROTIC ACIDURIA
introduction of Purine and Pyrimidine metabolism, biosynthesis and degradation of nucleotides, biological functions and metabolic disorders, chemical analogues and therapeutic drugs, uric acid metabolism
Metabolism of amino acids (general metabolism)Ashok Katta
Metabolism of amino acids (general metabolism).
Part - I of amino acid metabolism.
This presentation covers Transamination, deamination, formation and Transport of Ammoniaand etc.
De novo synthesis of fatty acids (Biosynthesis of fatty acids)Ashok Katta
Synthesis of fatty acids in the body. Detailed pathway for de novo synthesis of fatty acids in the body including its energetic and regulation. also cover Multienzyme complex
ETC and Phosphorylation by Salman SaeedSalman Saeed
ETC and Phosphorylation lecture for Biology, Botany, Zoology, and Chemistry Students by Salman Saeed lecturer Botany University College of Management and Sciences Khanewal, Pakistan.
About Author: Salman Saeed
Qualification: M.SC (Botany), M. Phil (Biotechnology) from BZU Multan.
M. Ed & B. Ed from GCU Faisalabad, Pakistan.
The electron transport chain is comprised of a series of enzymatic reactions within the inner membrane of the mitochondria, which are cell organelles that release and store energy for all physiological needs.
As electrons are passed through the chain by a series of oxidation-reduction reactions, energy is released, creating a gradient of hydrogen ions, or protons, across the membrane. The proton gradient provides energy to make ATP, which is used in oxidative phosphorylation.
Title: Sense of Smell
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 primary categories of smells and the concept of odor blindness.
Explain the structure and location of the olfactory membrane and mucosa, including the types and roles of cells involved in olfaction.
Describe the pathway and mechanisms of olfactory signal transmission from the olfactory receptors to the brain.
Illustrate the biochemical cascade triggered by odorant binding to olfactory receptors, including the role of G-proteins and second messengers in generating an action potential.
Identify different types of olfactory disorders such as anosmia, hyposmia, hyperosmia, and dysosmia, including their potential causes.
Key Topics:
Olfactory Genes:
3% of the human genome accounts for olfactory genes.
400 genes for odorant receptors.
Olfactory Membrane:
Located in the superior part of the nasal cavity.
Medially: Folds downward along the superior septum.
Laterally: Folds over the superior turbinate and upper surface of the middle turbinate.
Total surface area: 5-10 square centimeters.
Olfactory Mucosa:
Olfactory Cells: Bipolar nerve cells derived from the CNS (100 million), with 4-25 olfactory cilia per cell.
Sustentacular Cells: Produce mucus and maintain ionic and molecular environment.
Basal Cells: Replace worn-out olfactory cells with an average lifespan of 1-2 months.
Bowman’s Gland: Secretes mucus.
Stimulation of Olfactory Cells:
Odorant dissolves in mucus and attaches to receptors on olfactory cilia.
Involves a cascade effect through G-proteins and second messengers, leading to depolarization and action potential generation in the olfactory nerve.
Quality of a Good Odorant:
Small (3-20 Carbon atoms), volatile, water-soluble, and lipid-soluble.
Facilitated by odorant-binding proteins in mucus.
Membrane Potential and Action Potential:
Resting membrane potential: -55mV.
Action potential frequency in the olfactory nerve increases with odorant strength.
Adaptation Towards the Sense of Smell:
Rapid adaptation within the first second, with further slow adaptation.
Psychological adaptation greater than receptor adaptation, involving feedback inhibition from the central nervous system.
Primary Sensations of Smell:
Camphoraceous, Musky, Floral, Pepperminty, Ethereal, Pungent, Putrid.
Odor Detection Threshold:
Examples: Hydrogen sulfide (0.0005 ppm), Methyl-mercaptan (0.002 ppm).
Some toxic substances are odorless at lethal concentrations.
Characteristics of Smell:
Odor blindness for single substances due to lack of appropriate receptor protein.
Behavioral and emotional influences of smell.
Transmission of Olfactory Signals:
From olfactory cells to glomeruli in the olfactory bulb, involving lateral inhibition.
Primitive, less old, and new olfactory systems with different path
- 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
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.
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!
Ethanol (CH3CH2OH), or beverage alcohol, is a two-carbon alcohol
that is rapidly distributed in the body and brain. Ethanol alters many
neurochemical systems and has rewarding and addictive properties. It
is the oldest recreational drug and likely contributes to more morbidity,
mortality, and public health costs than all illicit drugs combined. The
5th edition of the Diagnostic and Statistical Manual of Mental Disorders
(DSM-5) integrates alcohol abuse and alcohol dependence into a single
disorder called alcohol use disorder (AUD), with mild, moderate,
and severe subclassifications (American Psychiatric Association, 2013).
In the DSM-5, all types of substance abuse and dependence have been
combined into a single substance use disorder (SUD) on a continuum
from mild to severe. A diagnosis of AUD requires that at least two of
the 11 DSM-5 behaviors be present within a 12-month period (mild
AUD: 2–3 criteria; moderate AUD: 4–5 criteria; severe AUD: 6–11 criteria).
The four main behavioral effects of AUD are impaired control over
drinking, negative social consequences, risky use, and altered physiological
effects (tolerance, withdrawal). This chapter presents an overview
of the prevalence and harmful consequences of AUD in the U.S.,
the systemic nature of the disease, neurocircuitry and stages of AUD,
comorbidities, fetal alcohol spectrum disorders, genetic risk factors, and
pharmacotherapies for AUD.
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
micro teaching on communication m.sc nursing.pdfAnurag Sharma
Microteaching is a unique model of practice teaching. It is a viable instrument for the. desired change in the teaching behavior or the behavior potential which, in specified types of real. classroom situations, tends to facilitate the achievement of specified types of objectives.
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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.
Tom Selleck Health: A Comprehensive Look at the Iconic Actor’s Wellness Journeygreendigital
Tom Selleck, an enduring figure in Hollywood. has captivated audiences for decades with his rugged charm, iconic moustache. and memorable roles in television and film. From his breakout role as Thomas Magnum in Magnum P.I. to his current portrayal of Frank Reagan in Blue Bloods. Selleck's career has spanned over 50 years. But beyond his professional achievements. fans have often been curious about Tom Selleck Health. especially as he has aged in the public eye.
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Introduction
Many have been interested in Tom Selleck health. not only because of his enduring presence on screen but also because of the challenges. and lifestyle choices he has faced and made over the years. This article delves into the various aspects of Tom Selleck health. exploring his fitness regimen, diet, mental health. and the challenges he has encountered as he ages. We'll look at how he maintains his well-being. the health issues he has faced, and his approach to ageing .
Early Life and Career
Childhood and Athletic Beginnings
Tom Selleck was born on January 29, 1945, in Detroit, Michigan, and grew up in Sherman Oaks, California. From an early age, he was involved in sports, particularly basketball. which played a significant role in his physical development. His athletic pursuits continued into college. where he attended the University of Southern California (USC) on a basketball scholarship. This early involvement in sports laid a strong foundation for his physical health and disciplined lifestyle.
Transition to Acting
Selleck's transition from an athlete to an actor came with its physical demands. His first significant role in "Magnum P.I." required him to perform various stunts and maintain a fit appearance. This role, which he played from 1980 to 1988. necessitated a rigorous fitness routine to meet the show's demands. setting the stage for his long-term commitment to health and wellness.
Fitness Regimen
Workout Routine
Tom Selleck health and fitness regimen has evolved. adapting to his changing roles and age. During his "Magnum, P.I." days. Selleck's workouts were intense and focused on building and maintaining muscle mass. His routine included weightlifting, cardiovascular exercises. and specific training for the stunts he performed on the show.
Selleck adjusted his fitness routine as he aged to suit his body's needs. Today, his workouts focus on maintaining flexibility, strength, and cardiovascular health. He incorporates low-impact exercises such as swimming, walking, and light weightlifting. This balanced approach helps him stay fit without putting undue strain on his joints and muscles.
Importance of Flexibility and Mobility
In recent years, Selleck has emphasized the importance of flexibility and mobility in his fitness regimen. Understanding the natural decline in muscle mass and joint flexibility with age. he includes stretching and yoga in his routine. These practices help prevent injuries, improve posture, and maintain mobilit
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
Pulmonary Thromboembolism - etilogy, types, medical- Surgical and nursing man...VarunMahajani
Disruption of blood supply to lung alveoli due to blockage of one or more pulmonary blood vessels is called as Pulmonary thromboembolism. In this presentation we will discuss its causes, types and its management in depth.
2. Points to be covered
Over view
Redox potential .Arrangement of components in ETC.
Coupled nature of respiration in mitochondria
Substrate Level Phosphorylation
Components of electron transport chain
P : O ratio and its calculation
Mechanism of oxidative phosphorylation
Inhibitors
3. An Overview
• Biological oxidations are catalyzed by intracellular enzymes,
to obtain energy.
• Electron Transport: Electrons carried by reduced
coenzymes (NADH or FADH2) are passed sequentially
through a chain of proteins and coenzymes ( electron
transport chain)to O2 .
• Oxidative Phosphorylation: Coupling e- transport,
oxidation and ATP synthesis (Phosphorylation) .
• Site of oxidative phosphorylation : inner mitochondrial
membrane (Eukaryotic cells)
4. Redox potential E₀
Redox potential or oxidation –reduction potential
is a quantitative measure of the tendency of redox
pair to loose or gain electrons.
Free energy changes can be expressed in terms of
Free energy change is proportionate to the
tendency of reactants to donate or accept the
electrons.
−ve redox potential
+ve redox potential
5. Arrangement of components in ETC
• Arranged in the order of increasing redox potential.
From electro − ve to electro + ve
Redox pair E₀
NAD⁺/NADH -0.32
FMN/FMNH₂ -0.22
Pyruvate/Lactate -0.19
Cytochrome c Fe³⁺/Fe²⁺ +0.07
O₂/ H₂O + 0.82
6. NADH & FADH₂
C
Carbohydrates
Lipids
Proteins
TCA cycle
Oxidation is coupled to
phosphorylation of ADP
Respiration (consumption
of oxygen)proceeds only
when ADP is present
•Amount of o₂ consumed
depends on amount of
ADP added .
Coupled nature of respiration in mitochondria.
Energy rich
A pair of
electrons
Having high
transfer potential
O₂ H₂O
Donated to
Free energy
liberated
Utilized for ATP
generation
7. Substrate Level Phosphorylation
Glyceraldehyde -3-Phosphate+ NAD ⁺+ Pi 1~3 bis phosphoglycerate + NADH
1~3bis phosphoglycerate + ADP 3 Phosphoglycerate + ATP
2) 2~ Phosphoenol pyruvate Pyruvate + ATP
3) α-ketoglutarate + NAD⁺ + CoA Succinyl ~ CoA + NADH + H⁺
Succinyl~CoA + GDP + Pi Succinate + GTP
1~
ADP
Synthesis of ATP without involving electron transport chain.
8. Definition
• The process of synthesizing ATP from
ADP and Pi coupled with the electron
transport chain is known as oxidative
phosphorylation.
9. Oxidative Phosphorylation
• Energy is released when electrons are transported
from higher energy
NADH/FADH2 to lower energy O2 .
• This energy is used to phosphorylate ADP.
• This coupling of ATP synthesis to NADH/FADH2
oxidation is called oxidative phosphorylation.
• Oxidative phosphorylation is responsible for 90 % of
total ATP synthesis in the cell.
Site …................ Mitochondria
11. Impermeable
to ions and
most other
compounds
In inner
membrane
knobs
Mitochondrion
The enzymes responsible for electron transport and
oxidative phosphorylation present in mitochondria.
12. ∙∙∙∙∙∙∙
∙∙ ∙∙∙∙ ∙∙
∙
Structure of Mitochondria
Β-oxi
TCA
Phosphorylating subunits
Matrix
Inner Membrane
Outer membrane
Cristae
(B)
(B)
Inner
membrane
F1 subunit
Fo subunit
ATP synthase
13. Electron Carriers
NAD+
FMN
FeS
ubiquinoneFAD FeS
Cyt b
FeS Cyt c1 Cyt c Cyt a Cyt a3
1/2 O2
ubiquinone
NAD+ or FAD
There are 2 sites of entry
for electrons into the
electron transport chain:
Both are coenzymes for
dehydrogenase enzymes
The transfer of electrons is not directly to oxygen but
through coenzymes
14. Components of electron transport chain
• Components are arranged in order of
increasing redox potential.
• From electro –ve to +ve
• NAD⁺/NADH to O₂/H₂O
• -0.32 to +0.82
16. Complex I
• NADH -ubiquinone oxidoreductase (NADH
dehydrogenase )
• Embedded in mitochondrial membrane
• Transfers electrons from NADH to Q
• NADH transfers two electrons as a hydride ion (H: H:-)
to FMN
• Electrons, one at a time , are passed through Complex
I to Q via FMN and iron -sulfur proteins
17. • Succinate -ubiquinone oxidoreductase
(or succinate dehydrogenase complex)
• Accepts electrons from succinate and catalyzes the reduction of Q to QH 2
• FAD of II is reduced in a 2 -electron transfer of a hydride ion from
succinate
• Complex II does not contribute to proton gradient , but supplies
electrons from succinate
Complex II
19. Iron-sulfur centers (Fe-S) have prosthetic groups
containing 1-4 iron atoms
Iron-sulfur centers transfer only one electron, even if
they contain two or more iron atoms.
E.g., a 4-Fe center might cycle between redox states:
Fe+++, Fe++
1 (oxidized) + 1 e- Fe+++
1, Fe++ (reduced)
Iron-sulfur Centers (clusters)
20. biquinone
QCoenzyme Q CoQ
Other names and abbreviations:
FAD FeS
FeS
FeS
FMN
NAD+
ubiquinone
Cyt b
ubiquinone
O
O
CH3O
CH3CH3O
(CH2 CH C CH2)nH
CH3
OH
OH
CH3O
CH3CH3O
(CH2 CH C CH2)nH
CH3
2 e-
+ 2 H+
coenzyme Q
coenzyme QH2
Free CoQ can undergo a 2 e-
oxidation/reduction:
Q + 2 e- + 2 H+ QH2.
Ubiquinone or Coenzyme Q
21. Coenzyme Q
• Coenzyme Q (CoQ, Q or ubiquinone) is lipid-
soluble. It dissolves in the hydrocarbon core of
a membrane.
• The only electron carrier not bound to a
protein. It is a mobile electron carrier.
• It has ability to accept electrons in pairs and
pass them one at a time through a
semiquinone intermediate to complex III.
• This is called Q cycle.
23. Cytochromes are electron carriers containing
heme . Heme in the 3 classes of cytochrome (a, b,
c) differ in substituents on the porphyrin ring.
Some cytochromes(b,c1,a,a3) are part of large
integral membrane protein complexes.
Cytochrome c is a small, water-soluble protein.
Cytochrome c is also a mobile electron carrier.
Cytochromes
24. Oxidative Phosphorylation
Oxidation and phosphorylation are coupled processes
by proton gradient across the inner mitochondrial
membrane.
Mechanism of oxidative phosphorylation :
1. Chemical hypothesis.
2. Chemiosmotic
25. Chemical Hypothesis
• A series of phosphorylated high energy
intermediates are formed and utilized for ATP
synthesis.
• 1.Only substrate level phosphorylation can be
explained.
• 2.Lacks experimental evidence.
26. Chemiosmotic Theory
Proposed by Peter Mitchell in 1961
Most accepted.
It explains how transport of electrons through
respiratory chain is utilized to produce ATP from
ADP +Pi
Explains action of uncouplers.
27. NAD+
FMN
FeS
ubiquinoneFAD FeS
Cyt b
FeS Cyt c1 Cyt c Cyt a Cyt a3
1/2 O2
ubiquinone
I
II
III IV
Mitochondrial Complexes
NADH Dehydrogenase
Succinate
dehydrogenase
CoQ-cyt c Reductase
Cytochrome Oxidase
NADH
29. Complex I
Complex I: NADH-CoQ oxidoreductase
*Entry site for NADH + H+
*Contains:
Fe-S cluster (non-heme protein)
flavin mononucleotide phosphate (FMN)
Coenzyme Q (free in membrane)
*Net reaction: NADH + H+ + CoQ ---> NAD+ + CoQH2
*ΔG°' = -81.0 kJ/mol
•complex I pumps protons outside the mitochondria
•ATP produced
30. Complex II
Complex II: Succinate-CoQ reductase
*Entry site for FADH2
*Contains:
Fe-S cluster (non-heme protein)
Coenzyme Q (free in membrane)
*Net reaction: Succinate + CoQ --> Fumarate +CoQH2
*ΔG°' = -13.5 kJ/mol
* Conversion of succinate to fumarate is reaction of TCA
cycle and is catalyzed by succinate dehydrogenase
Not a proton pump
No ATP produced
31. Complex III
Complex III: CoQH2-cytochrome c oxidoreductase
*Contains:
cytochrome c (free in membrane)
cytochrome b
cytochrome c1
Several Fe-S cluster (non-heme protein)
*Net reaction: CoQH2 + 2 cyt c [Fe ³⁺] ---> CoQ + 2 cyt
c[Fe ²⁺ ] + 2 H+
*ΔG°' = -34.2 kJ/mol
•Complex III pumps protons outside the mitochondria
•ATP produced.
32. Complex IV
Complex IV: cytochrome oxidase
*Contains:
cytochrome a
cytochrome a3
Copper
*Net reaction: 2 cyt c [Fe ²⁺]+ 1/2 O2 + 2 H+ ---> 2
cyt c[Fe ³⁺] + H2O
*ΔG°' = -110.0 kJ/mol
* Complex IV pumps protons outside the
mitochondria
* ATP produced
33.
34. III IVI
F1
Fо
Q
NADH+H⁺ NAD
II
Succinate Fumarate
4H⁺4H⁺
2H⁺
Cyt c H⁺
H⁺
H⁺
H⁺
Uncouplers
H⁺
H⁺
½O₂ + 2H⁺ H₂O
Inter membrane
space +++++ +++++++ +++ +++
Inner
mitochondrial
membrane
Mitochondrial
matrix
ADP + Pi ATP
The chemiosmotic theory 0f oxidative phosphorylation
−− −−−−− − −− −−−
35. Salient features of chemiosmotic theory
Inner mitochondrial membrane is impermeable to ions
particularly to protons (H
Complex I, III, and IV acts as a proton pump.
Pumping of electrons results in: a) Electrical gradient : as
protons are +vely charged , inter membrane space becomes
more electro +ve as compare to mitochondrial matrix or in
other words mitochondrial matrix becomes electro –ve. Thus
potential difference is produced. b)Chemical gradient :
accumulation of H+ causes lowering of pH in inter membrane
space where as mitochondrial matrix become alkaline as
compare to inter membrane space . Thus chemical gradient is
produced.
Hence this is called electrochemical or proton gradient.
36. Salient features of chemiosmotic theory
The electrochemical potential difference across the membrane,
once established as a result of proton translocation , inhibits
further transport of reducing equivalents through the respiratory
chain unless discharged by back translocation of protons across the
membrane through ATP synthase .
This in turn depends on availability of ADP and Pi.
37. P : O Ratio
Refers to number phosphate group incorporated into
ATP for every atom of O₂ consumed in oxidation.
OR
Represents number of ATP synthesized per pair
electron carried through ETC.
P:o = 3 Mitochondrial oxidation of NADH
NADH + H⁺ +½ O₂ + 3ADP + 3Pi 3 NAD + 3ATP +
4 H₂O
P:o = 2 Mitochondrial oxidation of FADH₂
38. Calculation of the P:O ratio
molecules of ADP phosphorylated
P:O ratio = -----------------------------------------
atoms of oxygen reduced
Complex I II III IV
#H⁺ translocated/2e 4 0 4 2
Since 4 H⁺ are required for each ATP synthesized:
For NADH: 10 H⁺ translocated / O (2e⁻ )
P/O = (10 H ⁺/ 4 H⁺ ) = 2.5 ATP/O
For succinate substrate = 6 H⁺ / O (2e⁻ )
P/O = (6 H⁺ / 4 H⁺ ) = 1.5 ATP/O
39. Energetics of oxidative phosphorylation
NAD⁺/NADH 1/2O₂/H₂O
—O.32 +0.82
1/2O₂ + NADH + H⁺ H₂O + NAD⁺
Potential difference 1.14V = 52 cal/mol
3 ATP = 21.9cal
Efficiency of energy conservation
21.9 x 100
52
42%
40. Sites of ATP Synthesis
• Site 1---Oxidation of FMNH₂ by Coenz Q
• Site2--- Oxidation of cyt.b by cyt.c₁
• Site3---cyt. Oxidase reaction (bet. a+a₃)
• When difference of redox potential between
two redox pairs >0.15 volts
• Or ∆ G > 7.3 Kcal
41. NADH
FMN,Fe.SComplex I
ADP + Pi
ATP
QFAD
Fe.S
Complex II
Fatty acyl coA
Glycerol -3-Phosphate
Succinate
CCcccCCyt b, Fe-S, cytC₁Complex III
ADP + Pi
ATP
Cyt. C
Heme a heme a₃
Cu Cu
O₂
ADP + Pi
ATP
Complex IV
Piericidine
Amobarbital
Rotenone
Oligomycin
BAL(dimercaprol)
Antimycin A
Sites of ATP synthesis & Inhibitors
H₂S,
CO, CN
Uncouplers
42. Uncouplers
Can uncouple or delink
Allow oxidation without phosphorylation
No ATP formation
O₂ Consumption
Eg.1)2-4 dinitro phenol(DNP) - lipid
soluble uncouple
2) Thermogenin- Physiological
uncoupler
3) High doses of Aspirin
Tri-fluorocarbamylcynide phenylhydrazone
(FCCP) : 100 times more effective as an than
dinitrophenol (DNP)
43. IONOPHORES
• Ionophores—Lipid soluble compounds
permiability of lipid bilayers
to certain ions.
Eg. Valinomycin & Nigercin
Permit potassium ion to penetrate
through mitochondrial membrane discharging
the membrane potential..
K⁺ ions exchanges with H⁺
44. Rate limiting factors
• Availabity of ADP & Substrate.
• Availabity of Substrate.
• Availibity of ADP only.
• Availibity of O₂ only.
• Capacity of respiratory chain.
45. The inner mitochondrial membrane is impermeable.
Therefore ,NADH produced in cytosol cannot directly enter
mitochondria.
• Two shuttle systems for transport of reducing equivalents:
• Transport : Cytosol To Mitochondria but not vice versa
(1) Glycerol phosphate shuttle : insect flight muscles
(2) Malate Malate-aspartate shuttle : predominant in liver and
other mammalian tissues
Aerobic Oxidation of Cytosolic NADH