Membranes Flashcards
(131 cards)
1
Q
Metabolic Functions
A
• Major energy store
• Converted to ketone
bodies in fasting
• Energy production
2
Q
Structural Functions
A
- Membrane components
* Protein modification
3
Q
4 Functions of Lipids
A
1) Structural functions
2) Metabolic functions
3) Cell signalling
4) Precursor molecules
4
Q
Unsaturated Fats
A
Contain double bonds
‘Un’saturated because double bond kicks out 2 hydrogens
Melting point increase with # of double bonds
Solubility decreases with # of double bonds
5
Q
Saturated Fats
A
Tail contains as many hydrogens bonded to carbon as possible
6
Q
Glycerol formula
A
HO - CH2 - CH - CH2 - OH
|
OH
*Fatty acid chains bind to alcohol group
- three alcohol groups
- 3 fatty acid tails can bind via ESTER bonds
7
Q
What type of bond binds fatty acid chains to _______ in triacylglycerol
A
- fatty acid tail bound to gylcerol OH group
- bound via ESTER bonds
8
Q
Triacylglycerol
A
TAG = FA triester of glycerol
Most abundant type of lipid.
TAG is neutral but hydrophobic.
9
Q
Fats Provide: (2)
A
- 6X the energy of an equal weight of
hydrated glycogen because of specialized cells called ADIPOCYTES are used to
store TAG.
10
Q
Glycerophospholipids
A
- Also known as PHOSPHOGLYCERIDES
- Consist of glycerol‐3‐ phosphate with FAs esterified to C1 & C2
- 2 FA’s + 1 PO4- group
11
Q
Gycerophospholipid structure
A
Fatty Acid -------- G
L
Fatty Acid -------- Y
(unsaturated) C
E
R ---PO4- ---- OH
O (head group)
L
12
Q
Head groups of glycerophospholipids (5)
A
(GECIS)
1) Glycerol
2) Ethanolamine
3) Choline
4) Inositol
5) Serine
13
Q
Plasmalogens
A
- glycerophospholipids
- C1 substituent linked via ETHER linkage instead of an ESTER linkage.
- Ethanolamine, choline and
serine are common head
groups (X).
14
Q
Why are Ether bonds found more readily in extremophile bacteria?
A
ether bonds are more resistant to
hydrolysis than the ester bonds of
glycerophospholipids
15
Q
Sphingolipids
A
- Major membrane components
- Derivatives of the amino alcohol
SPHINGOSINE (SPE) - N‐acyl FA derivatives of SPE are called
CERAMIDES
16
Q
3 major types of Sphingolipids
A
1) Sphingomyelins
2) Cerebrosides
3) Gangliosides
17
Q
Sphingomyelins
A
- Type of sphingolipid
- most common type, ceramides carrying phosphoCHOLINE or phosphoETHANOLAMINE head groups.
18
Q
Cerebrosides
A
ceramides with a single sugar as a head group (glucose or galactose most common).
19
Q
Gangliosides
A
most complex, ceramides with oligosaccharides attached (6% of brain lipid).
20
Q
Cholesterol
A
- 4 ringed structure
- Contains OH group
- contributes to membrane fluidity
21
Q
Arachodonic Acid turns into (3)
A
Eicosanoids
Prostoglandin
Leukotreine
22
Q
NSAID’s
A
Can block the conversion of Arachodonic Acid –> Prostoglandins and/or Eicosanoids
23
Q
Nucleus:
A
site of DNA and RNA synthesis
a) Nucleoli: ribosome synthesis
24
Q
Energy converting organelles
A
a) Mitochondria: site of cellular respiration
b) Chloroplasts (plant cells only): photosynthesis
25
Rough ER
ribosome attachment and protein synthesis
1) Attached ribosomes: synthesize secretory, ER, lysosomal, Golgi and plasma membrane proteins.
2) Free ribosomes synthesize: cytosolic, nuclear, mitochondorial and chloroplast proteins.
26
```
Smooth ER:
General functions (2) + Compartment functions (3)
```
1) lipid metabolism
2) packaging of secretory proteins; & detoxification.
1) Drug detoxification by increasing solubility
2) Glycogen catabolism
3) Ca2+ storage
27
Golgi Complex:
processing & packaging newly synthesized proteins and lipids
28
Lysosomes (animal cells only):
Degradation of macromolecules
29
Peroxisomes: (2)
1) generating & degrading H2O2
| 2) FA oxidation
30
Vacuoles (2)
1) storage
| 2) plant cell turgidity
31
Functions of Membranes (5)
1) Delineation & compartmentalization ex) plasma & organelle membranes
2) Location of specific function e.g. proteins in specific organelle membranes (ETC in mitochondria).
3) Regulation of transport
4) Detection & transmission of signals
5) Cell‐cell communication
32
Phospholipid bilayer (4)
1. Forms spontaneously
2. Composition asymmetric across bilayer
3. Capable of lateral diffusion but very little
transverse diffusion (measured by membrane bleaching)
4. Membrane fluidity is affected by
temperature & lipid composition
33
OH of cholesterol binds to (ETHER/ESTER) bond of phospholipid
OH binds with ESTER bond on phospholipid
34
3 types of membrane associated proteins
1) Integral proteins
2) Peripheral proteins
3) Covalently associated membrane proteins
35
Types of Integral proteins (3)
1) monotopic (bound inside one leaflet)
2) Singlepass (single a-helix)
3) Multipass (multiple a-helix)
4) Multi-subunit (contains residues)
36
Functions of membrane proteins (4)
```
[TREC]
Transport
Receptors
Cell recognition and adhesion
Electron carriers
```
37
NH3+ and COO- placement
NH3+ : Outside the cell (extracellular space)
| COO- : Inside the cell cytosol
38
Cell fusion experiment
- showing that membrane proteins have lateral movement capability
- Flourescently labelled proteins on mouse and human cells
- Cells fused together
- membrane proteins mixed together
39
Radioactive Iodine experiment
- shows that membrane proteins can flip-flop (transverse movement) from inner leaflet to outer, and vis versa
40
Types of attachment to membrane proteins (2)
3 AA's they typically attach to
1) N-linked attachment
2) O-linked attachment
AST -> NOO attachment
1) Asparagine; N-linked
2) Serine; O-linked
3) Threonine; O-linked
41
4 common sugars on glycoproteins
1) Mannose
2) Galactose
3) Glucosamine
4) Sialic Acid
42
Passive Transport
1) Movement of substance from region of high to low concentration down its concentration gradient
2) No input of energy
43
Rules for Simple Diffusion
CAN PASS
- Small, uncharged, polar: Water
- Lipid soluble: O2, N2, anaesthetic
CANT PASS
- Ions
- Large, uncharged, polar: Glucose, Sucrose
44
What can pass the lipid membrane
CAN PASS
- Small, uncharged, polar: Water
- Lipid soluble: O2, N2, anaesthetic
45
What CANT pass the lipid membrane
CANT PASS
- Ions
- Large, uncharged, polar: Glucose, Sucrose
46
Structure of many anaesthetic
Aromatic --Ester/amide link---NR2
47
How do local Anaesthetics work?
1) BH+ --> B + H+
2) uncharged B can move through lipid
3) B + H+ --> BH+
4) BH+ can block Na channels preventing depolarization
*patient would be injected with a weak base*
48
Energetics of Transport
| Charged vs. Uncharged
Uncharged: depends solely on its [ ] gradient
Charged: depends on electrochemical
gradient which is generated by [ ] and
electric charge gradients
49
Energetics of Transport
The free energy change when diffusion of an uncharged species occurs depends on the magnitude of the [ ] difference
deltaG = RT ln[Cin]/[Cout] *x2.3 changes to log10 [Cin]/[Cout]
- If [Cin]/[Cout] is less than unity influx of solute will be favoured and since log[Cin]/[Cout] is negative, deltaG will also be negative.
- neg deltaG means equilibrium moves towards 0
50
Types of facilitated diffusion (2)
1) Carrier proteins
2) Ion Channels
a) ion gated channels
b) voltage or ligand gated ‐ neuron function
51
Types of Ion channels
Facilitated diffusion
1) Ion gated channels
2) voltage or ligand gated channels
52
Classes of transport channels
1) Uniport - glucose transporter
2) Co-transport
a) Symport
b) Anti-port
53
Active transport definition
Movement of substances across a membrane against its concentration gradient requires the input of energy.
54
When does active transport allow intake of nutrients and when does it remove nutrients?
1. Allows up‐take of nutrients even when [in]/[out]> 1
2. Allows removal of molecules even when [in]/[out] <1
* allows for uptake/removal of nutrients against gradient
55
4 classes of ATP-ion pumps
1. P‐Class
2. V‐Class
3. F‐Class
4. ABC ATPases (ATP binding cassette)
56
P-class Ion Pumps
- On Plasma membrane
- transporter reversibly phosphorylated to alter conformation
- e.g. Na+/K+ ATPase
57
V-class Ion Pump
‐ found in organelles and vesicles (V); ATP is hydrolyzed and used to generate a proton gradient; no phosphorylation occurs - e.g. lysosomal proton pump
58
F-class Ion Pump
- proton gradient is used to synthesize ATP - e.g. F1‐F0 ATP pump of the mitochondrial inner membrane
59
ABC ATPases (ATP binding cassette)
a) Cystic fibrosis‐Transmembrane Conductance Regulator (CFTR)
- Transport of Cl‐
- ATP dependent‐ mechanisms unknown;
common genetic disease
b) Multidrug resistance
- ATP powered export of drugs;
- Some cancers overexpression occurs
60
2 types of Active Transport
1) Direct Active Transport
| 2) Indirect Active Transport
61
Direct Active Transport
Energy directly used to move a substance to generate an electrochemical gradient
- Ex) Na/K pump
- 3Na out cell ; 2K into cell
- decreases (+) charge within cell
62
Indirect Active Transport
Transport of one substance against its [ ] gradient is coupled to, and driven by,
movement of second substance down its gradient.
- Ex) Na/Glucose pump
- Na high outside cell due to Na/K pump, allows for Na to flow down grandient into cell, and glucose goes against gradient
- no ATP used in this mechanism
63
Enterocyte uptake
- cotransport of Na and glucose
- indirect active transport from Na/K pump
- Basal border of enterocyte has passive carrier for glucose transport into bloodstream
- Na/K continually exports Na
- high intracellular K has no important features in enterocyte
64
Role of ER in Protein Structure
| Site of: (4)
1. Proper folding
a) Chaperone proteins
b) Unfolded protein response
2. Disulphide bond formation
3. Formation of multi‐subunit proteins
4. In initial steps in the addition of carbohydrate
65
Chaperones
Re-fold improperly folded proteins
| If not possible, elicit unfolded protein response
66
Unfolded Protein Response
When there are lots on improperly folded proteins, cells elicit unfolded protein response which is apoptosis/blebbing
67
Glycosylation
First addition of sugars (N or O-linked) added to the Cis-Golgi Complex
N‐linked on Asn
O‐linked on Ser/Thr
Sugars are continually added throughout GC, sulphication occurs at trans-GC
68
Retention and retrieval of ER proteins
Soluble ER proteins are retrieved from cis‐GC via retrograde transport.
1. Protein binds specific receptor
2. Triggers retrograde transport
3. pH of ER lumen dissociates protein‐receptor complex
69
Sorting of Golgi proteins
1. Tag for retention and retrieval.
| 2. Size of transmembrane domain.
70
Targeting of soluble lysosomal proteins
1. Oligosaccharide tag targets transport.
2. Mannose‐6‐phosphate added IN Golgi.
3. Transported to endosome which becomes a lysosome
71
2 types of targeting of secretory proteins
1. Constitutive secretion e.g. ECM glycoproteins
2. Regulated secretion e.g. insulin and
neurotransmitters
72
Constitutive Secretion
Type of targeting of secretory proteins
a) Secretory vesicles bud from trans‐GC
b) Vesicles fuse with plasma membrane
73
Regulated Secretion
Type of targeting of secretory proteins
a) Secretory vesicles bud from trans‐GC
b) Mature vesicles accumulate
c) In response to a trigger (e.g. Ca2+) vesicles fuse with plasma membrane
74
```
Targeting of Proteins From
Free Ribosomes (2)
```
1) Nuclear proteins
| 2) Mitochondrial and chloroplast proteins
75
Nuclear Protein targeting
Targeted by a nuclear localization sequence in the protein per se.
76
Mitochondria and Chloroplast targeting
Targeted by an N‐terminal signal sequence which is cleaved after import in the organelle.
77
3 Typical Signal Peptides
1) Retention in lumen of ER
- (short @ C‐terminal)
2) Import into nucleus
‐ (moderate @ mid)
3) Import into mitochondria
- (long @ N‐terminal)
78
Exocytosis is stimulated by:
Ca2+
79
Polarized secretions only occur on the (Basal/Ventral) surface
Basal Surface
80
Phagocytosis vs Pinocytosis
Phago: ingestion of large particles
Pino: ingestion of extracellular fluid
81
Receptor mediated endocytosis
1) Clatherin dependent
2) receptor-ligand complex endocytosed
3) receptor is recycled
4) ligand is hydrolyzed
82
Transcytosis
Movement of material across a cell which involves both endocytosis and exocytosis
Movement THROUGH a single cell. Endocytosis on one surface and exocytosis through the other
83
4 types of vesicle formation
1) Clathrin
2) COP-I
3) COP-II
4) SNAP/SNARE
84
COP-I
Bidirectional between golgi and ER
Retrograde within Golgi
Coat assembly mediated by ARF
85
COP-II
Anterograde: RER to Golgi
| Sar-1 GTP-binding proteins mediates assembly
86
SNARE hypothesis
t-SNARE and v-SNARE interaction
rab GTPase associated with hydrolysis
SNAPs and NSF bind for fusion - driven by ATP hydrolysis
87
Lysosomes (3)
1) derived from late endosomes which have inactive enzymes
2) ATP-dependedn proton pump in membrane lowers the pH to 4-5 to activate enzymes
3) contain acid hydrolases
88
Lysosome functions (4)
1) Phagocytosis
2) Receptor-mediated endocytosis
3) Autophagy
4) Extracellular digestion
89
Autophagy
Degredation of damaged intracellular structures
90
Mammary Secretion process (5)
1) Exocytosis (lactose, glucose, ions, etc)
2) Lipid pathway (TAG and P-lipids move from SER to apical membrane)
3) Apical transport (Na, K, Cl, H2O)
4) Transcytosis (move intact proteins [IgA])
5) Paracellular route (Na, Cl)
91
Paracellular
Movement in between cells without going through them
92
Endocrine
Long travel distance usually via blood between secretory and target cell
93
Paracrine
Secretory and target cell are close
94
Autocrine
same cell makes and receives signal
95
What do signals do (4)
1) Cellular growth rate
2) Metabolism
3) Gene expression
4) Cell fate during development
96
2 types of extracellular signals
1) Water-soluble signals
| 2) Lipid-soluble signals
97
Water soluble signals (examples)
Growth factors
| Some hormones
98
Lipid soluble signals (examples)
Steroid hormones
99
Properties of Membrane Receptors (5)
1) specificity for ligand
2) Affinity
3) Conformational change
4) Receptor/Ligand interactions
5) Can be regulated in conditions change
100
G-protein-linked receptor examples (3)
1) Rhodopsin
2) Olfactory receptors
3) B-andregenic receptors
101
G-protein linked receptor structure (3)
1) 7-transmembrane domains
2) intracellular loop for g-protein binding
3) ligand binding site (extracellular)
102
G-proteins (GTP vs GDP)
```
GTP = active
GDP = inactive
```
103
G-protein pathway
1) Ligand binds (extracellular)
2) G-alpha releases GDP to GTP (active)
3) G-alpha attaches to protein (creates 2nd messenger)
4) G-beta-gamma binds to separate protein (inhibitory)
5) G-alpha hydrolyzes GTP to GDP (inactive)
6) G-alpha reconnects to beta-gamma
104
3 types of 2nd messengers
1) cAMP
2) IP3
3) Ca2+
105
cAMP Signalling
1) G-alpha binds to Adenylyl Cyclase (AC)
2) AC converts ATP to cAMP
3) cAMP activates PKA
4) PKA phosphorylates
106
Phosphorylation causes changes in (3)
1) metabolism: glycogen synthesis
2) growth rate
3) gene expression
107
Phosphodiesterase
Breaks phosphodiester bonds
| Breaks cAMP to AMP
108
DAG/IP3, Ca2+ and G-proteins
1) G-alpha activates Phospholipase C (PLC)
2) Activated PLC breaks down phospholipid (PIP2) into
a) DAG - Diacylglycerol
b) IP3 - Inositol-triphosphate
109
IP3
1) Binds to Ca2+ channels in ER and releases Ca2+
2) Ca2+ bind to Calmodulin regulatory protein
3) Ca2+/calmodulin complex regulates variety of Ca2+/calmodulin dependent kinases
4) these Kinases phosphorylate proteins causing changes in cellular activity
110
Nitric Oxide Mechanism
NO activated Guanylyl Cyclase (GC) and creates 2nd messenger cGMP
111
Types of Kinase-Associated Receptors (2)
1) Tyrosine Kinase Receptors
| 2) Serine/Threonine Kinase Receptors
112
Tyrosine Kinase Receptors
Autophosphorylation of tyrosine tails
Activates:
a) Phospholipase C pathway
b) Sos/GRB2 pathway
113
Sos/GBR2 Pathway
Stimulates Ras pathway
Ras converts GDP to GTP (active)
Ras-GTP activated MAPK pathway (MAPK = nuclear changes)
GAP hydrolyses Ras-GTP to GDP (inactive)
114
Serine/Threonine Kinase Receptors (STK-Rs)
Type-II receptor
| SMAD and coSMAD is 2nd messenger and enters nucleus
115
Adrenalin acts on (2)
Also known as Epinephrine
Secreted from Adrenal gland
Acts on B-andregenic receptor
1) Cardiac Cells
2) Liver cells (hepatocytes)
116
4 aspects of Peptidoglycan layer
1) N-acetyl glucosamine (NAG)
2) N-acetyl muramic acid (NAM)
3) Tetrapeptides
4) Inter-bridge peptides
117
3 types of peptidoglycan inhibitors
All are antibiotics (i think)
1) Cycloserine
2) Bactitracin
3) Penicillin/Cephalosporin/Vancomycin
118
Cycloserine
Inhibits precursor formation
Site: inside cell
Inhibits: L-Alanine --> D-Alanine
119
Bacitracin
Inhibits transport and pep. formation
Site: Cell membrane
Inhibits: Transfer of pep.
120
Penicillins/Cephalosporins/Vancomycin
Inhibits crosslinking of peptidoglycan
| Site: Outside cell
121
B-lactams
4-membered cyclic amide ring
| inhibit crosslinking
122
B-lactams Antibiotics
| Cephlosporins, penicillins, penems, monobactams
B-lactams attached to
6-membered ring: Cephlosporins
5-membered ring: Penicillins
5 membered ring: Penems
No rings: Monobactams
123
Cellulose
Long unbranched polymer of glucose
124
Pectins
Branched polysaccharides - gel like and trap water
125
Extensins
Glycoproteins crosslinks to each other and cellulose to provide mechanical support
126
Lignins
Insoluble polymer of aromatic alcohols which makes large cross-linked networks in woody tissue
127
Expansins
Proteins that mediate cell wall loosening and expansion
128
Sequential sysnthesis of plant cell wall (3)
1) Middle Lamella
2) Primary cell wall
3) Secondary cell wall
129
Common Fungal Pathogens (5)
1) Dermatophytes
2) Candida
3) Aspergillus
4) Cryptococcus
5) Rhizopus
130
Amphotericin B
Creates pores in the membrane of plant cells
131
Echinocandins
- Increase in chitin
- Kills hyphae at growth tips - buds fail to separate from mother cell (apical meristem)
- yields osmotically sensitive fungal cells
