CELL Phsyiology Flashcards
1
Q
The four broad categories of cells
A
- Epithelial cells
- Connective tissue cells
- Nerve cells
- Muscle cells
2
Q
The phospholipids in the phospholipid bilayer are
A
Amphipathic
3
Q
Amphipathic
A
Having a hydrophilic head and a hydrophobic tail
4
Q
Membrane cholesterol
A
- Found primarily in the outer cell membrane
- Cholesterol is slightly amphipathic.
- Functions to maintain membrane fluidity
5
Q
Two classes of membrane proteins
A
- Integral membrane proteins
2. Peripheral membrane proteins
6
Q
Integral membrane proteins
A
Embedded in the membrane or membrane spanning (so-called “transmembrane” proteins)
Amphipathic (contain polar and non-polar domains/amino acids)
7
Q
Peripheral membrane proteins
A
Not amphipathic
Lie on membrane surface, bound to polar regions of integral proteins
Primarily on cytosolic surface
8
Q
The three types of junctions
A
- Desmosomes
- Tight junctions
- Gap junctions
9
Q
Desmosomes
A
Structural characteristics: - Adjacent cells separated by ~ 20 nm - Form “dense plaques” - Firm attachment between cells gives structural integrity
Protein components:
- Cadherins (extend into extracellular
space and bind with cadherins from
adjacent cells) - Keratin (anchors desmosome to
cytoskeleton)
10
Q
Tight junctions
A
Structural characteristics:
- No space between adjacent cells - Occurs in band around entire cell
- Common in epithelia
Protein components:
- Complex >40 known proteins
- Occludins
- Claudins
11
Q
Gap junctions
A
Structural characteristics:
- Adjacent cells separated by ~ 2-4 nm
- Form pores between cells, allowing
passage of ions and small molecules
Protein components:
- Connexins
12
Q
Structure-Function relationship of cell membranes
A
- Regulate passage of substances into and out of cell (part 2)
- Detect chemical messengers arriving at the cell surface (part 3)
- Link adjacent cells together
- Anchor cells to extracellular matrix
13
Q
The nucleus
A
- Largest organelle (typically one/cell)
- Primary function: storage of genetic information (DNA!), in the form of chromatin
- Surrounded by membrane = nuclear envelope, with openings called nuclear pores
Nuclear pores facilitate…
- Passage of RNA into the cytoplasm
- Entrance of proteins that modulate gene expression
- Contains nucleolus: site of ribosomal RNA synthesis and protein components of ribosomes
14
Q
Ribosomes
A
- Smallest (~20 nm) and most abundant organelle (~10 million)
- Primary function: “protein factory”
– translates RNA into protein - No surrounding membrane (comprised of proteins and RNA)
- Critical component of the central dogma of molecular biology (Watson & Crick)
DNA»_space;» RNA»_space;> PROTEIN
nucleus. Ribosome
- Found floating free in the cytoplasm or attached to endoplasmic reticulum
- Free ribosomes primarily synthesize cytosolic proteins - Membrane-bound ribosomes primarily synthesize membrane bound proteins
15
Q
Found floating free in the
- Free ribosomes primarily synthesize
A
- cytoplasm or attached to endoplasmic reticulum
cytosolic proteins - Membrane-bound ribosomes primarily synthesize membrane bound proteins
16
Q
Endoplasmic reticulum
A
Contains SMOOTH and ROUGH ER
17
Q
SMOOTH ER
A
- continuous with rough ER and nuclear envelope
- Contains enzymes associated with for e.g. fatty acid synthesis. Stores and releases calcium*
18
Q
ROUGH ER
A
- “rough” appearance comes from
adherent ribosomes - Site of protein synthesis. Proteins
synthesized in lumen distributed to
other organelles or secreted
19
Q
Golgi apparatus
A
- Structure: series of membranous sacs (“cisternae”), forming a cup shape. Polar, with a “cis” and “trans” face.
- Function: cellular “post office”; modifies and sorts proteins arriving from the rough ER; distributes them to other organelles or to the membrane for secretion
20
Q
Endosomes
A
Structure: small membrane-bound vesicle
Function: Sorting vesicular “traffic” in the cell.
21
Q
Lysosomes
A
- cellular stomach
- acidic environment. Contains digestive enzymes
breakdown:
- damaged organelles
- engulfed bacteria
- engulfed debris form dead cells
Important for cells defence systems
22
Q
Peroxisomes
A
Cellular “reprocessing plant”
Nueatral PH, contain oxygen consuming enzymes, generating H2O2
Breakdown:
- fatty acids (beta-oxidation)
- detoxification of alcohol
23
Q
Mitochondria
A
Structure: double-membrane bound, interconnected rod-like structures. Inner membrane folded into “cristae”, giving distinct appearance
Function: “powerhouse” of the cell; transfers energy present in nutrients to adenosine triphosphate (ATP) in a process called cellular respiration
24
Q
Three classes of cytoskeleton are
A
- Actin filaments
- Intermediate filaments
- microtubules
25
Actin filaments
G-actin form polymer of two twisting chains, forming F-actin
26
Intermediate filament
Twisted strands of multiple possible proteins (keratin, Desmond, laminin)
27
Microtubules
Hollow tubes, formed form tubular subunits
28
Does Diffusion across the membrane occur through the lipid bilayer, and/or via proteins
YES
29
What determines a modules ability to diffuse across the membrane
Polarity
30
Nonpolar molecules diffuse across membranes relatively ________ (e.g. oxygen, carbon
dioxide, fatty acids)
Quickly
31
Polar molecules diffuse across membranes relatively ________ (e.g. ions [K+], glucose)
Slowly
32
Diffusion equilibrium
When one compartment of high conc. And another compartment of low conc. Combine to to reach in the middle and reach an equilibrium
33
Net flux
The direction of the diffusion is a product of the balance between one way flux between compartments
34
The greater the surface area,
The greater area for diffusion to take place, therefore faster net flux
35
Large differences in
| concentration will drive _______ diffusion
Greater
36
Different molecules diffuse at
Different rates
37
Large portions diffuse _____ and ions diffuse _______
Slow
Fast
38
Ion channels
Transmembrane proteins that allow for ions to diffuse across them
39
Ion channels form
Pores
40
The small diameter of the ion channel pores
Prevent larger molecules form passing through
41
Ion channel show selective permeability to specific ions,this is determines by
1) channel diameter
2) charge of the polypeptides
3) number of water molecules associated with ion
42
Channel gating
Diffusion’s of ions through ion channels is controlled
43
Three types of channel gating
1) ligand gated
2) voltage gated
3) mechanically gated
44
Ligand gated
binding of specific molecule to channel causes conformational change
45
voltage-gated
a change in membrane potential causes conformational change
46
Mechanically gated
a physical change in the membrane (e.g. stretch)
47
Transporters
Membrane proteins that facilitate movement across the membranes
48
Protein-mediated transport
Protein-mediated movement of ions, amino acids and other small molecules occurs
49
The general model for protein-mediated transport across membranes includes three steps:
1) Solute binding to specific site on protein surface exposed to extracellular fluid
2) Conformation change in transporter, exposing bound solute to intracellular fluid
3) Dissociation of solute from binding site into the intracellular fluid
50
Between protein0mediated transport and ion channels, which is moves 1000X more molecules
Ion channels
51
If ion channels are selective, are proteins mediated transporters also selective?
YES
52
Magnitude of flux through transporters dependent on four factors:
1) solute concentration
2) affinity of transporter for solute
3) numbers of transporters in the membrane
4) rate at which the transporter goes through conformational change
53
Why is the rate of flux for protein mediated transport limited
Because cells express a certain number of transporters
54
For diffusion, why is the flux into the cells limitless?
Because the flux into the cell is directly proportional to extra cellular conc.
55
Facilities diffusion / “downhill” via membrane portion
- ‘stop’ when concentration equalized
| - does not require ATP
56
active transport / “uphill” via membrane protein
- often referred to as “pumps”
| - Requires energy to overcome concentration difference
57
Is protein mediated transport passive or active
Active
58
Energy required to power active transport (protein mediated transport) can comes from two known sources:
1) the direct use of ATP > primary active transport
| 2) the use of an electrochemical gradient across a membrane > secondary active transport
59
Protein-mediated transport > primary active transport
- Requires ATP - “ATPase” transporters hydrolyse ATP
1) provides energy
2) phosphorylates protein, a covalent modulation that changes protein confirmation
60
Na+/K+ - ATPase pump is primary active transport or secondary active transport ?
Primary active transport
61
Na+/K+-ATPase pump
- present in all cells
- moves Na+ from intracellular to extracellular fluid
- moves K+ from extracellular to intracellular fluid
- Maintains relatively high levels of intracellular K+, and low Na+
- Moves three Na+ ions out of the cell and brings in two K+ ions = net transfer of positive charge
62
Steps for Na+/K+-ATPase pump (5 steps)
1) 3 sodium ions bind to high-affinity binding sites on intracellular surface of ATP-bound protein (Potassium ions will not bind to their binding sites because they are in a low-affinity state
2) Sodium binding activates ATPase activity of transporter.
Surface of protein is phosphorylated and ADP is released
3) Protein phosphorylation causes conformational change, exposing bound sodium to the extracellular environment.
Conformational changes also changes affinity for sodium, releasing it.
4) Conformational change increases affinity for potassium, which bind to the extracellular surface of the protein, triggering release of phosphate
5) Release of phosphate returns protein to original confirmation, resulting in reduced affinity for potassium and its release into the cell.
63
Other examples of ion pumps that include primary active transport
- Ca2+-ATPase
| - H+ -ATPase
64
Ca2+-ATPase
important in maintaining cellular calcium homeostasis, an important regulatory signal in the cell
65
H+-ATPase
moves H+ out the cell, therefore important in maintaining cellular pH
66
Secondary active transport
Movement of ion down electrochemical gradient coupled to transport of other (organic) molecule, such as glucose or an amino acid
67
Example of secondary active transport
- Sodium flows along concentration gradient into cell (“downhill”)
- Solute pulled inside against its concentration gradient (“uphill”)
- Cycle of steps similar to primary active transport, except no ATP consumed
- (Maintenance of sodium’s concentration gradient depends on primary active transport)
68
Endocytosis:
membrane envaginations enclose small volume of extracellular fluid, which are taken into the cell
69
Exocytosis:
intracellular membrane-bound vesicles fuse with the plasma membrane
and release their contents into the extracellular fluid
70
Three types of endocytosis
1) Pinocytosis
2) Phagocytosis
3) Receptor-mediated endocytosis
71
Pinocytosis
- Nonspecific
- includes water and whatever solutes are present
- Vesicle fuses with lysosome, where contents are hydrolyzed
72
Phagocytosis
- Specific (involves interaction between particle and cell surface)
- Unique to specialized cells of the immune system (phagocytes)
- Involves uptake of bacteria or cell debris from damaged tissue
- Internalized vesicle called a phagosome, fuses with lysosome, where
contents are hydrolyzed
73
Receptor-mediated endocytosis
- Specific and usually unique to cell function
- Cell surface receptors recognize high-affinity ligands
- Clustering of receptors allows selective concentration of endocytic vesicles without engulfing large amounts of extracellular fluid (as in pinocytosis)
- Can involve the recruitment of cytosolic clathrin, forming a clathrin-coated pit, which is then internalized
- Depending on cell-type and ligand, vesicle can have multiple fates including fusion with endosomes or lysosomes
- Receptor is often recycled back to the cell surface
74
Type of reception meditate endocytosis
Potocytosis
75
potocytosis
- Restricted to small molecules (e.g. vitamins)
- Generates relatively small vesicles called caveolae
- Contents delivered to the cytosol (rather than lysosomes, etc)
76
Two function of exocytosis
1) Replaces cell surface membrane lost during endocytosis
| 2) Allows secretion of membrane impermeable molecules into extracellular fluid
77
Epithelial cells line the
cavities and surfaces of vessels and organs
78
apical membrane
Surface facing hollow organ/tube
79
basolateral membrane
Opposite surface (typically adjacent to blood vessels)
80
Two possible pathways across epithelial membrane:
1) Paracellular pathway (between cells) 2) Transcellular pathway (through cell)
81
Paracellular pathway (between cells)
Movement limited by presence of tight junctions, limited to diffusion of water and small ions
82
Transcellular pathway (through cell)
- Utilizes processes of diffusion and protein-mediated transport just described Often involves flow against a concentration gradient, requiring ATP
83
How do cells communicate with each other (intercellular communication)?
Receptors
84
Once a cell has received a signal, it must be “processed”, this is called
signal transduction
85
How do cells process signals (intracellular communication)?
- Lipid-soluble messengers
- Water-soluble messengers
→ second messengers
86
Cells receive signals from other cells via
receptor proteins → Depending on the signal, receptors can be located on the outside of the cell, or inside it
87
Water-soluble signal
- Most common
| - Bind to plasma transmembrane receptors
88
Lipid-soluble signal
- Can diffuse through membrane
- Bind to intracellular receptors
- Generally transduce signal via change in gene expression
89
Ligand-receptor interactions dictate
cellular signaling
90
Cell signaling depends on ligand-receptor interactions, including:
1) Specificity
2) Affinity
3) Saturation
4) Competition
91
Specificity
The ability of a receptor to only bind a limited number of ligands
92
Affinity
Strength of ligand binding to receptor
93
Saturation
Extent to which receptors are bound by ligand (100% = fully saturated)
94
Competition
Presence of other ligands which “compete” for receptor binding sites
95
Competition
Presence of other ligands which “compete” for receptor binding sites
96
___________ between ligands is the molecular basis for many drugs
Competition
97
Intercellular signalling can be regulated at the receptor level. What’s the primary way to regulate them?
Primary way to regulate receptors is through their number
- down regulation
- up regulation
98
Down-regulation
- a lowering of the number of target cell receptors
- Can occur in response to sustained high levels of signal (negative feedback)
- Reduces cell response to frequent/intense stimulation
- Common mechanism to down-regulate plasma membrane receptors is through
internalization (includes receptor-mediated endocytosis)
99
Up-regulation
- An increase in the number of target cell receptors
- Can occur in response to sustained low levels of signal (positive feedback)
- Increases cell response to low-level stimulation
- Can occur through increased insertion of receptor-containing vesicles into the cell
membrane
100
The process of signal transduction translates a signal into a
cellular response
101
Signal transduction pathway depends
| on
signal and receptor location
102
Cellular response:
1) Change in membrane properties
2) Cellular metabolism
3) Secretory activity
4) Rate of proliferation/differentiation
5) Contractility or other activity
103
Examples of Transduction of lipid-soluble signals
steroid hormones, thyroid hormone, and vitamin A
104
What is transduction of lipid-soluble signals primarily mediated by ?
Nuclear receptors, leading to gene expression
105
Transduction of lipid-soluble signals
1) Circulating signal diffuses from circulation across membrane into cell
2) Signal enters nucleus and binds receptor*
3) ligand-receptor complex functions as a transcription factor, changing expression (mRNA) level of target gene
4) Change in mRNA abundance effects change in protein level, leading to cellular response
106
Transduction of water-soluble signals
- More complex!
- Signal transduction occurs in two phases:
1) binding of signal to receptor (first messenger)
2) signals generated by receptor activation (second messenger)
- Many second messenger systems relying on phosphorylating proteins to effect change
- Protein phosphorylation changes its structure, eliciting a response (can be
activation or inhibition)
- Enzymes that phosphorylate proteins are called protein kinases
- Phosphorylation typically occurs at tyrosine reside, therefore called receptor tyrosine kinases
- Multistep pathways can be complex...
107
Examples of transduction of water-soluble signals
- Examples include polypeptide hormones (e.g. insulin) and neurotransmitters
108
Second messenger systems can create cascades that
amplify a signal
109
What does the signal that’s created by second messenger systems creating a cascade allow?
allows signalling molecules at low extracellular concentrations to have large effects
e.g., one molecule of epinephrine can stimulate the liver to generate and release 108 molecules of glucose
110
Common mechanisms of water-soluble ligand signaling
1) Receptors that function as ion channels
2) Receptors that function as enzymes
3) Receptors that interact with cytoplasmic kinases (called janus kinases)
4) Receptors that interact with G-proteins (aka g-protein coupled receptors)
111
1) Receptors that function as ion channels
“Ligand-gated ion channel”
Water soluble Messenger attaches to receptor which opens the ion channel, allowing for the flow of ions, leading to the cells response
112
2) Receptors that function as enzymes
Water soluble messenger attaches to receptor which causes tyrosine kinase to phosphorylate a docking protein, this leads to the cells response
113
3) Receptors that interact with cytoplasmic kinases (called janus kinases)
- Membrane receptor has no intrinsic enzyme activity, but upon activation of the receptor, an associated kinase will be turned on
Water soluble messenger attaches to receptor which causes the Janus kinase to make ATP and protein react together in a rxn, this leads to the cells response
114
4) Receptors that interact with G-proteins (aka g-protein coupled receptors)
- Largest group of receptors for water-soluble signals
| - G-proteins “couple” receptor with effector proteins to generate second messengers
115
G-proteins are
complex mediators of signaling through G-protein coupled receptors
116
G proteins are made up of three subunits
- Alpha subunit
| - Beta-gamma subunit complex
117
Alpha subunit
binds GDP/GTP
118
Beta-gamma subunit complex:
Beta-gamma subunit complex: help anchor alpha subunit in membrane
119
Receptors that interest with G-proteins
- Ligand binding changes affinity for alpha subunit to GTP away from GDP
- GTP-GDP exchange causes dissociation between alpha subunit and beta-gamma complex
- Activated alpha subunit binds to effector protein to initiate cellular response
120
Three major families of G-proteins exist:
| - Defined by second messenger system they modulate and how
- Gi : inhibits production of cyclicAMP
- Gs : activates production of cyclicAMP
- Gq : activates phospholipase C
121
cAMP is a
potent second messenger, the levels of which are tightly regulated
122
cAMP
- cAMP acts by activating cAMP-dependent protein kinase (aka protein kinase A; PKA)
- PKA has multiple targets, meaning it can elicit multiple responses in the same cell (and different response in different cells, depending on the suite of target proteins expressed)
123
What is the synthesis of cAMP catalyze by ?
Synthesis of cAMP from ATP is catalyzed by adenylyl cyclase
124
Breakdown of cAMP is catalyzed by
cAMP phosphodiesterase
125
Can calcium act as a second messenger ?
YES
126
How do signals cause the cytosolic Ca2+ concentration to increase?
- Activation of plasma membrane Ca2+ channel (This could be by signal binding as shown, or also via a change in membrane potential in the case of a voltage-gated Ca2+ channel)
- Opening of Ca2+ channel on the ER membrane
- Active transport of Ca2+ out of the cell blocked by a second messenger (not shown)
127
How does increased Ca2+ concentration elicit a cellular response?
Typically via binding to proteins and activating them, e.g. Calmodulin
128
Cessation of intracellular signaling is required to prevent
overstimulation of the cell
129
Cessation of intracellular signalling is most commonly occurs at the level of receptor activation
- decreased concentration of signal (breakdown/uptake/diffusion)
- Change in receptor conformation (e.g. via phosphorylation)
> changes signal binding affinity
> prevents further G-protein binding to the
receptor
- Receptor mediated endocytosis
