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Lecture 1.
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LSB231- Physiology:
Lecture 1.
• Part A: The Cell
– organelles
g
– cytoskeleton
• Part B: The Plasma Membrane
– membrane structure
– membrane proteins
– membrane transport
• Part C: Metabolism and Energy
– types of metabolism
– role
l off ATP
– sources of ATP
LSB231- Physiology:
Lecture 1.
Learning Objectives – Part A
• Identify each of the major cellular organelles
• Describe
D ib the
th ffunction
ti off each
h organelle
ll
• Membrane bound.
• Analogous to organs
found within the
body.
p
• Each serve specific
functions.
• Supported by
cytoskeleton.
Organelles
• Nucleus
• Endoplasmic
reticulum
• Golgi apparatus
• Mitochondria
• Lysosomes
• Peroxisomes
P i
The Nucleus
• Bounded by nuclear
envelope
l with
ith pores.
The Nucleus
• Bounded by nuclear
envelope
l with
ith pores.
• Contains DNA in the
form of chromatin.
The Nucleus
• Bounded by nuclear
envelope
l with
ith pores.
• Contains DNA in the
form of chromatin.
• Mayy display
p y
nucleolus.
The Nucleus
• Bounded by nuclear
envelope
l with
ith pores.
• Contains DNA in the
form of chromatin.
• Mayy display
p y
mRNA
RNA
nucleolus.
• Site of DNA synthesis.
• Site of transcription.
Endoplasmic Reticulum
• Outer membrane
continuous with
nuclear envelope.
Endoplasmic Reticulum
• Outer membrane
continuous
ti with
ith
nuclear envelope.
• May be characterised
as either
– “smooth” or
– “rough”
• depending upon
presence of
p
ribosomes.
Endoplasmic Reticulum
• Rough
g ER (RER)
( ) tRNA mRNA
– site of translation for
proteins that are aa
transported out of the
cell or into other
organelles.
ll Peptides
– Synthesis of phospholipid.
Endoplasmic Reticulum
• Smooth ER (SER)
– lipid metabolism
– cholesterol/steroid
h l l id
synthesis
– drug
d g metabolism
t b li (li
(liver))
– calcium storage
(eg sarcoplasmic reticulum
of skeletal muscle cells)
Ca2+
Golgi Apparatus
• Receives packages of
proteins from RER.
• Modifies proteins:
– p
post-translational
modifications.
– Glycosylation.
• Sorts and packages
p ote s:
proteins:
– vesicles delivered to other
g
organelles or p
plasma
membrane.
Mitochondria
Matrix
Inner membrane
Mitochondria
• Bound by single
lysosomes
membrane.
b
• Contain acidic
environment.
g
• Serve digestive function.
• Contain acid hydrolases.
– Proteases,
Proteases lipases etc
etc.
• Especially abundant in
phagocytic cells.
cells Neutrophil leukocyte
– eg. Neutrophils
Peroxisomes
• Bound by single
membrane.
b
• Contain enzymes required
for metabolism of toxins.
• Peroxisomal Disorders:
– Can cause serious
developmental and
neurological defects.
– eg. X-linked Peroxisomes in liver cell
adrenoleukodystrophy
Cytoskeleton
• Internal scaffold of cells.
• Controls cell shape.
• Controls cell transport.
• C i t of:
Consists f
– microfilaments (actin
polymer)
– microtubules (tubulin
polymer)
– intermediate filaments
(vary in composition: eg.
eg Actin filaments
Keratins). in fibroblasts
Microfilaments
G-actin
G actin (monomer)
• Composed of
polymerised actin.
F-actin (polymer)
Microfilaments
• Composed of or = G-actin (monomer)
polymerised actin.
• Associated with
numerous actin-
binding proteins, eg. F-actin (polymer)
myosin.
Microfilaments
• C
Composed d off
polymerised actin.
• Associated with
numerous actin-
binding proteins, eg.
myosin.
•Human Neutrophil seeks
• Essential for bacteria
regulating
g g changes
g in for permanent
•for
cell shape. relationship
•Enjoys food and long
– Amoeboid motilityy amoeboid crawls around
– Muscle contraction. the body
Microfilaments
• Composed of
polymerised actin.
• Associated with
numerous actin-
binding proteins, eg.
myosin.
• Essential for
regulating changes in
cell shape. Movie of Leukocytes hunting
bacteria
– Amoeboid motility ...if
if you don’t
don t come to the
– Muscle contraction. lecture you don’t get to see
the movie!!
Microtubules
• Composed of
polymerised
l i d ttubulin.
b li
Microtubules
• Composed of
polymerised
l i d ttubulin.
b li
• Associated with motor
proteins eg. kinesin.
Microtubules
• Composed of
polymerised
l i d ttubulin.
b li
• Associated with motor
proteins eg. kinesin.
pp
• Support cell structure.
• Provide paths for
intracellular
transport.
– Eg.
Eg Neuro
Neuro-transmitters
transmitters.
Intermediate Filaments
• Composition varies
according
di to
t cell
ll ttype.
• Less dynamic than
microfilaments and
microtubules.
• “Tough” insoluble
fibres.
Intermediate Filaments
• Composition varies
according
di to
t cell
ll ttype.
• Less dynamic than
microfilaments and
microtubules.
• “Tough” insoluble
fibres.
• Example:
– keratins in epithelial
cells.
Intermediate Filaments
• Composition varies
according
di to
t cell
ll ttype.
• Less dynamic than
microfilaments and
microtubules.
• “Tough” insoluble
fibres.
• Example: Human corneal epithelial
cells stained with antibody
– keratins in epithelial
to keratin 3
cells.
Part B: The Plasma Membrane
Learning Objectives – Part B
• Describe the structure and identify the various components of the
plasma membrane
• Understand
d d and
dddescribe
b osmolarity
l
• Double layer of
phospholipid
h h li id and d
cholesterol.
Polar
Non-polar
Membrane Structure
• Double layer of
phospholipid
h h li id and d
cholesterol.
Membrane Structure
Crystal of lipophilic dye
• Double layer of
phospholipid
h h li id and d
cholesterol.
• Highly dynamic.
Fluid Mosaic Model
• Double layer of
phospholipid
h h li id and d
cholesterol.
• Highly dynamic.
• Accessoryy
molecules:
– proteins
p
• integral
• peripheral
– carbohydrates
Membrane Proteins
• Roles of membrane
proteins:
t i
• Structural support.
• Communication.
• Channels.
• Gates.
• Pumps.
Transmembrane protein
Membrane Proteins
• Communication.
• Provide receptors for
soluble ligands.
• eg.
g hormones.
h
Membrane Proteins
• Communication.
– Provide receptors for
soluble ligands.
• Provide
P id receptorst ffor
other cells.
Membrane Proteins
• Communication.
– Provide receptors for
soluble ligands.
– Provide
P id receptorst ffor
other cells.
– Provide channels
between cells.
• Gap Junctions
between muscle cells.
Membrane Transport
• Size:
• Basic channels:
– Always open.
– Enable passive
t
transportt off
molecules across
plasma membrane by
diffusion.
– Restricted to
molecules of certain
physico-chemical
properties.
Membrane Transport
• Gated channels:
– Normally closed.
Membrane Transport
• Gated channels:
– Normally closed.
– Open in response to
appropriate
i t stimulus.
ti l
• Hormone
• Neurotransmitter
• Ion balance (voltage)
Diffusion
• Diffusion:
– movement of
substance along a
concentration
gradient.
– Results from random
collisions of
particles known as
p
Brownian Motion.
Osmosis
• Diffusion:
– movement of
substance along a
concentration
gradient.
• Osmosis:
– diffusion of water
along a concentration
gradient.
Osmosis
• Diffusion:
– movement of
substance along a
concentration
gradient.
• Osmosis:
– diffusion of water
along a concentration
gradient.
Osmosis
• Diffusion:
– movement of
substance along a
concentration
gradient.
• Osmosis:
– diffusion of water
along a concentration
gradient.
– Causes increase in
hydrostatic pressure
within the cell.
Osmolarity
• Facilitated diffusion:
– requires
concentration
gradient.
gradient
– Involves binding of
molecule to
transporter protein.
Facilitated Diffusion
• Facilitated diffusion:
– requires
concentration
gradient.
gradient
– Involves binding of
molecule to
transporter protein.
Facilitated Diffusion
• Facilitated diffusion:
– requires
concentration
gradient.
gradient
– Involves binding of
molecule to
transporter protein.
Facilitated Diffusion
• Facilitated diffusion:
– requires
concentration
gradient.
gradient
– Involves binding of
molecule to
transporter protein.
Facilitated Diffusion
• Facilitated diffusion:
– requires
concentration
gradient.
gradient
– Involves binding of
molecule to
transporter protein.
Facilitated Diffusion
• Facilitated diffusion:
– requires
concentration
gradient.
gradient
– Involves binding of
molecule to
transporter protein.
Facilitated Diffusion
• Facilitated diffusion:
– requires
concentration
gradient.
gradient
– Involves binding of
molecule to
transporter protein.
Facilitated Diffusion
• Facilitated diffusion:
– requires
concentration
gradient.
gradient
– Involves binding of
molecule to
transporter protein.
Facilitated Diffusion
• Facilitated diffusion:
– requires
i
concentration
g
gradient.
– Involves binding of
molecule to
t
transporter
t protein.
t i
– Example: Glucose
transport by GLUT
proteins (insulin
increases levels of
GLUT4).
GLUT4)
Active Transport
• Pumps:
– Useful for producing
concentration
gradients.
gradients
– Working against
entropy.
entropy
– Requires energy.
• ATP
• Ion gradient
Active Transport
• Pumps:
– Useful for producing
concentration
gradients.
gradients
– Working against
entropy.
entropy
– Requires energy.
• ATP
• Ion gradient
Active Transport
• Pumps:
– Useful for producing
concentration
gradients.
gradients
– Working against
entropy.
entropy
– Requires energy.
ATP
– Example with ATP.
ATP
Active Transport
• Pumps:
– Useful for producing
concentration
gradients.
gradients
– Working against
entropy.
entropy
– Requires energy. P
– Energy released from ADP
phosphate bond.
Active Transport
• Pumps:
– Useful for producing
concentration
gradients.
gradients
– Working against
entropy.
entropy
– Requires energy. P
– ADP released.
released
ADP
Active Transport
• Pumps:
– Useful for producing
concentration
gradients.
gradients
– Working against
entropy
entropy.
– Requires energy. P
– Energy used to alter
orientation of
protein.
p ADP
Active Transport
• Pumps:
– Useful for producing
concentration
gradients.
gradients
– Working against
entropy
entropy.
– Requires energy. P
– Molecules released.
released
ADP
Active Transport
• Pumps:
– Useful for producing
concentration
gradients.
gradients
– Working against
entropy.
entropy
– Requires energy.
– Phosphate released.
released
– Protein returns to
original ADP
conformation. P
Active Transport
• Pumps: • Calcium-ATPase
– Useful for producing – maintains low intracellular
concentration calcium concentration.
gradients
gradients.
• Sodium/potassium-
– Working against
ATPase
entropy
entropy.
– pumps 3 sodium ions out
– Requires energy. for every 2 potassium ions
– Examples: in.
Fluid Composition
Outside cells Inside Cell
• Na+ 140 mM 15 mM
• K+ 4 mM 150 mM
• Cl- 110 mM 10 mM
• Metabolism:
– refers to the collection of chemical reactions
that take place within a living structure.
Part C: Metabolism and Energy
• Metabolism:
– refers to the collection of chemical reactions
that take place within a living structure.
• Catabolic reactions:
– involve destruction of molecules.
Part C: Metabolism and Energy
• Metabolism:
– refers to the collection of chemical reactions
that take place within a living structure.
• Catabolic reactions:
– involve destruction of molecules.
• Anabolic
A b li reactions:
ti
– involve construction of molecules.
Energy
• Energy can neither be created nor
destroyed it simply changes form:
– First Law of Thermodynamics.
Energy
• Energy can neither be created nor
destroyed it simply changes form:
– First Law of Thermodynamics.
• Cells acquire energy via catabolism of
carbohydrates, fats and proteins.
Energy
• Energy can neither be created nor
destroyed it simply changes form:
– First Law of Thermodynamics.
• Cells acquire energy via catabolism of
carbohydrates, fats and proteins.
• Most of this energy is lost as heat.
heat
Energy
• Energy can neither be created nor
destroyed it simply changes form:
– First Law of Thermodynamics.
• Cells acquire energy via catabolism of
carbohydrates, fats and proteins.
• Most of this energy is lost as heat.
heat
• Remainder is stored in the form of
ATP.
ATP
Adenosine Triphosphate
Fats/Proteins
ATP
Krebs Cycle
ADP
Fats NADH + H+ and FADH2
Creatine-P
Oxygen Electron Transport
Chain
Mitochondria
Glycolysis
Matrix
Krebs Cycle
• Occurs within mitochondrial matrix.
• Pyruvate first converted to Acetyl-CoA.
• Acetyl-CoA
Acetyl CoA enables cycling of reactions between
citrate and oxaloacetate (Citric Acid Cycle).
• Requires aerobic conditions to proceed.
• Net yield for each cycle: 1 molecule of ATP.
Inner membrane
Electron Transport Chain
• Net yield:
– 3 molecules of ATP from each NADH + H+.
– 2 molecules of ATP from each FADH2.
Creatinine Phosphate
Glycolysis
Krebs Cycle ATP + Pi
ADP
ETC
Muscle Contraction/Relaxation
See you on Monday morning for your first Prac
But for now…
now