Na+- K+ ATPases are integral membrane proteins found in eukaryotic cells that utilize ATP to transport sodium and potassium ions across cell membranes. For every 3 sodium ions pumped out, 2 potassium ions are pumped in, generating ion gradients crucial for nerve and muscle function. Discovered in 1957, the sodium pump maintains cell resting potentials and drives secondary active transport of nutrients. Precisely regulating ion concentrations, it is vital for processes like fluid balance and is the body's largest consumer of ATP at rest. Inhibited by cardiac glycosides, it is a key drug target for heart conditions.
Objective of the Study:- Introduction, Structure of Sodium-Potassium Pump, History, Forms of the pump, Mechanism of working, Inhibition and Functions of the pump.
Objective of the Study:- Introduction, Structure of Sodium-Potassium Pump, History, Forms of the pump, Mechanism of working, Inhibition and Functions of the pump.
ATP synthase—also called FoF1 ATPase is the universal protein that terminates oxidative phosphorylation by synthesizing ATP from ADP and phosphate.
ATP Synthase is one of the most important enzymes found in the mitochondria of cells
Pentose phosphate pathway is also called Hexose monophosphate pathway/ HMP shunt/ Phosphogluconate pathway.
It is an alternative route for the metabolism of glucose.
It is more complex pathway than glycolysis.
It is more anabolic in nature.
It takesplace in cytosol.
The tissues such as liver, adipose tissue, adrenal gland, erythrocytes,testes and lactating mammary gland are highly active in HMP shunt.
It concern with the biosynthesis of NADPH and pentoses.
Biological oxidation (part - III) Oxidative PhosphorylationAshok Katta
Biological oxidation (part - III) Oxidative Phosphorylation
- Mechanism of Oxidative Phosphorylation
-- Chemiosmotic theory
-P:O Ratio
Substrate Level Phosphorylation
Shuttle Systems for Oxidation of Extramitochondrial NADH
ATP synthase—also called FoF1 ATPase is the universal protein that terminates oxidative phosphorylation by synthesizing ATP from ADP and phosphate.
ATP Synthase is one of the most important enzymes found in the mitochondria of cells
Pentose phosphate pathway is also called Hexose monophosphate pathway/ HMP shunt/ Phosphogluconate pathway.
It is an alternative route for the metabolism of glucose.
It is more complex pathway than glycolysis.
It is more anabolic in nature.
It takesplace in cytosol.
The tissues such as liver, adipose tissue, adrenal gland, erythrocytes,testes and lactating mammary gland are highly active in HMP shunt.
It concern with the biosynthesis of NADPH and pentoses.
Biological oxidation (part - III) Oxidative PhosphorylationAshok Katta
Biological oxidation (part - III) Oxidative Phosphorylation
- Mechanism of Oxidative Phosphorylation
-- Chemiosmotic theory
-P:O Ratio
Substrate Level Phosphorylation
Shuttle Systems for Oxidation of Extramitochondrial NADH
Contents –
INTRODUTION
PATHWAY OF ATP PRODUCTION
GLYCOLYSIS
PHASES
CITRIC ACID CYCLE
UTILIZATLION
ASSEMBLY OF MACROMOLECULES
ATP PROVIDES ENERGY BY GROUP TRANSFER
ATP ENERGIES ACTIVE TRANSPORT AND GROUP TRANSFER
GLOWING REPORTS OF ATP
CONCLUSION
REFERENCE
Gene Therapy, Somatic cell gene therapy, germ line gene therapy, classical gene therapy, non-classical gene therapy, targets of gene therapy, barriers of gene therapy, ex vivo gene therapy, in vivo gene therapy, vectors for gene delivery, antisense therapy
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
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.
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
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
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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
- Video recording of this lecture in English language: https://youtu.be/lK81BzxMqdo
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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.
2. Introduction
Na+-K+-ATPase is an integral
membrane protein found in the cells of
all higher eukaryotes.
It is responsible for translocating
sodium and potassium ions across the
cell membrane utilizing ATP as the
driving force.
3. For every three sodium ions pumped out of the cell, two potassium ions are
pumped in.
This transport produces both a chemical and an electrical gradient across
the cell membrane.
The electrical gradient is essential for maintaining the resting potential of
cells and for the excitable activity of muscle and nerve tissue.
The sodium gradient is used to drive numerous transport processes,
including the translocation of glucose, amino acids, and other nutrients into
cells.
4. Physiologically, Na+ - K+ ATPase present in organs such as the intestines and
the kidney regulates fluid reabsorption and electrolyte movement by
establishing an ionic gradient across epithelial membranes.
It is estimated that approximately 23% of the ATP consumed in humans at
rest is utilized by the sodium pump.
The Na+-K+-ATPase is a member of the P-type class of active cation
transport proteins of ATPases.
5. History
The sodium-potassium pump was discovered in 1957 by the Danish
scientist Jens Christian Skou.
He was awarded a Nobel Prize for his work in
1997.
6. Structure
The Na+ - K+-ATPase can function as an α β dimer.
Consists of –
- a catalytic α subunit with ten trans-membrane segments
(8 transmembrane α-helical segments and two large cytoplasmic
inclusions, and
- a single trans-membrane glycosylated β subunit (single
transmembrane helix and a large extracellular domain), required for
stabilization.
There are four isoforms of α(1-4) and three isoforms of β expressed in a
tissue-specific fashion.
7. The α subunit contains the ATP binding site, the phosphorylation site,
and amino acids essential for the binding of cations and cardiac
glycosides, which suggests that this subunit plays a major role in the
catalytic function of the enzyme.
The β subunit appears to be involved in maturation of the enzyme,
localization of the ATPase to the plasma membrane, and stabilization of a
K+-bound intermediate form of the protein.
8. Electrogenic pump
Drives 3 positively charged ions (Na+) out of the cell for every 2 it pumps in (K+).
It drives a net electrical charge across the membrane ,tending to create an
electrical potential, with cell’s inside being negative relative to outside.
This electrogenic effect of the pump ,however seldom directly contributes more
than 10% of the membrane potential.
9. Forms of sodium - potassium pump
Na+ - K+ ATPase exists in two forms-
E1 Form: E1 has an inward –facing high affinity Na+ binding site and reacts
with ATP to form the activated product E1~P only when Na+ is bound.
E2 form : E2 –P has an outward –facing high affinity K+ binding site and
hydrolyses to form Pi + E2 only when K+ is bound .
10. Mechanism
The (Na+-K+)-ATPase operates in accordance with
the following ordered sequencial reaction scheme:
1)E1.3Na+,which acquired its Na+ inside the cell, binds
ATP to yeild the tertiary complex E1.ATP.Na+
2)The tertiary complex reacts to form the high energy
aspartyl phosphate intermediate E1~P.3Na+
3)This high energy intermediate relaxes to its low
energy conformation ,E2-P.3Na+ and relaxes its bound
sodium outside the cell .
11. 4) E2-P binds 2K+ from outside the cell to form E2-P.2k+ .
5) The phosphate group is hydrolysed ,yeiding E2.2K+
6) E2.2K+ changes conformation , releases its 2K+ inside the cell
,and replaces its Na+ , thereby completing the transport cycle.
14. Exogenous
The Na/K+-ATPase is upregulated by cAMP. Thus, substances causing an increase in
cAMP upregulate the Na+/K+-ATPase.
These include the ligands of the Gs-coupled GPCRs.
In contrast, substances causing a decrease in cAMP downregulate the Na+/K+-ATPase.
These include the ligands of the Gi-coupled GPCRs.
15. Endogenous
The Na+-K+-ATPase can be pharmacologically modified by administrating
drugs exogenously.
For instance, Na+-K+-ATPase found in the membrane of heart cells is an
important target of cardiac glycosides ( for example digoxin and ouabain)
,inotropic drugs used to improve heart performance by increasing its force
of contraction.
16. Rate
In order to maintain a reasonable rate of transport, the free energies
of all its intermediates must be roughly equal.
If some intermediates were much more stable than others ,the stable
intermediates would accumulate, thereby severely reducing the overall
transport rate.
17. INHIBITION
The pump requires binding by Na+ , K+ and ATP for its operation. Therefore , if the
concentration of any of these substances is too low , the pump does not function.
When the temperature is reduced.
During oxygen lack.
Metabolic Poisons e.g. 2,4 DNP that prevents the formation of ATP.
18. Clinical Significance
Certain steroids derived from plants are potent inhibitors (Ki < 10 nM) of the Na+–K+
pump.
Digitoxigenin and ouabain are members of this class of inhibitors, which are known
as cardiotonic steroids because of their strong effects on the heart .
These compounds inhibit the dephosphorylation of the E2-P form of the ATPase
when applied on the extracellular face of the membrane.
19. Digitalis
Digitalis is a mixture of cardiotonic steroids derived from the dried leaf of the foxglove plant
(Digitalis purpurea).
The compound increases the force of contraction of heart muscle and is consequently a choice
drug in the treatment of congestive heart failure.
Inhibition of the Na1–K1 pump by digitalis leads to a higher level of Na1 inside the cell.
The diminished Na1 gradient results in slower extrusion of Ca21 by the sodium–calcium
exchanger.
The subsequent increase in the intracellular level of Ca21 enhances the ability of cardiac
muscle to contract.
20.
21. Ouabain
Ouabain is a cardiac glycoside that acts by inhibiting the Na+/K+-ATPase(but it is
not selective).
Once ouabain binds to this enzyme, the enzyme ceases to function, leading to
an increase of intracellular sodium.
This increase in intracellular sodium reduces the activity of the sodium-calcium
exchanger (NCX), which pumps one calcium ion out of the cell and three sodium
ions into the cell down their concentration gradient.
22. Therefore, the decrease in the concentration gradient of sodium into the
cell which occurs when the Na/K-ATPase is inhibited reduces the ability of
the NCX to function.
This in turn elevates intracellular calcium.
This results in higher cardiac contractility and an increase in cardiac vagal
tone. The change in ionic gradients caused by ouabain can also affect the
membrane voltage of the cell and result in cardiac arrhythmias.
24. Resting Potential
In order to maintain the cell membrane potential, cells keep a low
concentration of sodium ions and high levels of potassium ions within the
cell (intracellular).
The sodium-potassium pump mechanism moves 3 sodium ions out and
moves 2 potassium ions in.
Thus, in total removing one positive charge carrier from the intracellular
space .
25. Transport
Export of sodium from the cell provides the driving force for several
secondary active transporters membrane transport proteins, which
import glucose, amino acids, and other nutrients into the cell by use of the
sodium gradient.
26. Controlling Cell Volume
Failure of the Na+-K+pumps can result in swelling of the cell.
A cell's osmolarity is the sum of the concentrations of the various ion species
and many proteins and other organic compounds inside the cell.
When this is higher than the osmolarity outside of the cell, water flows into
the cell through osmosis. This can cause the cell to swell up and lyse.
The Na+-K+pump helps to maintain the right concentrations of ions.
Furthermore, when the cell begins to swell, this automatically activates
the Na+-K+ pump.
27. Functioning as signal transducer
Membrane protein can also relay extracellular ouabain - binding signalling
into the cell through regulation of protein tyrosine phosphorylation.
The downstream signals through ouabain-triggered protein
phosphorylation events include activation of the mitogen-activated protein
kinase (MAPK) signal cascades, mitochondrial reactive oxygen species (ROS)
production, as well as activation of phospholipase C (PLC) and inositol
triphosphate (IP3) receptor (IP3R) in different intracellular compartments.
Protein-protein interactions play a very important role in Na+-K+ pump-
mediated signal transduction.
28. For example, Na+-K+ pump interacts directly with Src, a non-receptor
tyrosine kinase, to form a signaling receptor complex.
Src kinase is inhibited by Na+-K+ pump, while, upon ouabain binding, the
Src kinase domain will be released and then activated.
Based on this scenario, NaKtide, a peptide Src inhibitor derived from Na+-
K+ pump, was developed as a functional ouabain-Na+-K+pump-mediated
signal transduction.
Na+-K+pump also interacts with ankyrin, IP3R, PI3K, PLC-gamma
and cofilin.
29. Controlling Neuron activity states
The Na+-K+ pump has been shown to control and set the intrinsic activity mode
of cerebellar Purkinje neurons, accessory olfactory bulb mitral cells and probably
other neuron types.
This suggests that the pump might not simply be a homeostatic, "housekeeping"
molecule for ionic gradients; but could be a computation element in
the cerebellum and the brain .
Indeed, a mutation in the Na+-K+ pump causes rapid onset dystonia parkinsonism,
which has symptoms to indicate that it is a pathology of cerebellar computation.
30. Furthermore, an ouabain block of Na+-K+pumps in the cerebellum of a live mouse
results in it displaying ataxia and dystonia.
Alcohol inhibits sodium-potassium pumps in the cerebellum and this is likely how
it corrupts cerebellar computation and body co-ordination.
The distribution of the Na+-K+ pump on myelinated axons, in human brain, was
demonstrated to be along the internodal axolemma, and not within the nodal
axolemma as previously thought.
31. Hormones
Major hormonal controls over pumps can be summarized as follows :-
Thyroid Hormones appear to a major player in maintaining steady state
concentrations of pumps in most tissues. This effect appears to result from
stimulation of subunit gene transcription.
Aldosterone is a steroid hormone with major effects on sodium homeostasis
.It stimulates both rapid and sustained increases in pump numbers within several
tissues. The sustained effect is due to enhanced transcription of genes for both
subunits.
32. Catecholamines have varied depending on specific hormones and tissue.
For example , dopamine inhibits Na+- K ATPase activity in kidney , while
epinephrine stimulates pump activity in skeletal muscles . These effects
seem to be mediated via phosphorylation or dephosphorylation of the
pumps.
Insulin is a major regulator of potassium homeostasis and has multiple
effects on sodium pump activity.
Within minutes of elevated insulin secretion, pumps containing alpha1 and
2 isoforms have increased affinity for sodium and increased turnover rate .
33. Sustained elevations in insulin causes upregulation of alpha-2 synthesis . In skeletal
muscle ,insulin may also recruit pumps stored in cytoplasm or recruit latent pumps
already present in membrane.
In 1997, he received one-half of the Nobel Prize in Chemistry "for the first discovery of an ion-transporting enzyme, Na+, K+-ATPase.“
Its discovery marked an important step forward in the understanding of how ions get into and out of cells, and it has particular significance for excitable cells such as nerve cells, which depend on this pump to respond to stimuli and transmit impulses.
These are the a subunit with a molecular mass of -113 kDa and the smaller glycosylated p subunit with a protein portion accounting for 35 kDa
Electrogenic- transport process results in a charge separation across the membrane.
These states have different tertiary structures , different catalytic activities and ligand specificities-
3)Na is transported through the membrane.
Interfere with dephosh step of transport
It is interesting to note
that digitalis was used effectively long before the discovery of the Na1–K1
ATPase. In 1785, William Withering, a British physician, heard tales of an
elderly woman, known as “the old woman of Shropshire,” who cured people
of “dropsy” (which today would be recognized as congestive heart failure)
with an extract of foxglove. Withering conducted the first scientific study
of the effects of foxglove on congestive heart failure and documented its
effectiveness.
(