[2] class3 Zaidi-transport Thru Membranes Flashcards
Interactions involved in lipid bilayer:
Electrostatic and non covalent
These are frequently glycosylated on the extracellular side of the lipid bilayer
Membrane lipids and proteins
Integral membranes
All the way transmembrane through lipid bilayer
Plasma membrane is semi
Semi-permeable
________facilitate movement of specific molecules across the Plasma membrane
Membrane transport proteins
Several hydrophobic residues for one protein the enters and leaves PM several times:
polytopic
Most transport proteins are:
Polytopic transmembrane integral membrane proteins
What is advantage to polytopic membrane proteins?
Allows more diversity in binding and conformational changes
What is permeable to PM??
Lipophilic molecules via diffusion - steroid hormones
What is impermeable to the PM?
Hydrophilic/ polar substances
How can polar/hydrophilic molecules pass through PM?
Needs a specific transport mechanism
What is used for specific transport of molecules across PM?
Membrane proteins
Polytopic, transmembrane, integral membrane proteins can:
Have multiple transport domains and can shape the cell to allow more substances to pass
What determines the ionic composition of the cell?
The activity and protein levels of specific transporters
What governs the biochemical/metabolic characteristics of a cell?
Expression of specific transporters
One way of regulating metabolism
Alteration in expression levels of transporters
Ion gradient are they static?
No dynamic, but they could be thought of static in regard to they are quickly reestablished [in the way they’re maintained]
Ion gradient allows for:
Membrane potential for AP
Brains uses _____ of energy
20%
Molecules move down a [ ] gradient by using energy stored in the gradient: Ex:
Passive transport ; ion channels
Molecules move against a gradient by using biochemical energy stored in ATP: EX:
Active transport; pumps/ ATPases
Energy independent movement of molecules down a gradient:
Passive transport
2 types of passive transport :
Simple diffusion
And
Facilitated diffusion
Molecules that are small, nonpolar, and uncharged move freely across PM unaided
Simple diffusion
Molecules that’re large and charged unable to cross the PM w/o assistance of channel or transporter
Facilitated diffusion
____________ of molecules is asso. W. free energy
Unequal distribution
What is used to set up an ion gradient across a semi-permeable membrane?
Energy
Ion gradients are generated by:
Membrane transporters [energy transducers]
Membrane transporters use energy from and store it as free energy of the gradient
ATP
Energy is minimum when [ ] across a semi-permeable mebrane is:
Equal
Positive free energy =
Active transport
- free energy =
Spontaneous
Movement of molecules against a gradient
Energy-dependent movement
2 diff. Types of proteins involved in energy-dependent movement:
P type ATPases
ATP binding cassette transporters
Ex of P type ATPases
Na+K+ ATPase
PM Ca++ ATPase [PMCA]
Muscle Ca++ ATPase SERCA
H+ K+ ATPase
Ex of ATP binding cassette transporter:
Multi-drug resistance protein
Uses energy from ATP hydrolysis to drive transport against gradient
ATP breaks into ADP and phosphate
Transporter forms covalent bond w/ phosphate to form EP intermediate
P type ATPases
Makes neurons and muscle cells electrically excitable, controls cell volume, drives the active transport of sugars and amino acids
25-40% of brain ATP used by
3Na+: 2K+ / mole ATP
Sodium pump
Ex of Na pump
Plant steroids- digitoxigenin and ouabain
called cardiotonic steroids d/t strong effect on heart
digitoxigenin and ouabain
Mixture of cardiotonic steroids
Digitalis
Cardiac glycosides that inhibit Na+K+ ATPase activity
ouabain and digitoxigenin
How does Digitoxigenin and ouabain work:
- Increase Na+ levels in cell: this reduces activity of antiporter Na+Ca++ exchanger
- This increase Ca++ ICF
- This Ca+ increases contractile force of cardiac muscle
Ex of Ca++ pumps:
Plasma mebrane Ca++ ATPase- PMCA
Sarco-endoplasmic reticulum Ca++ ATPase- SERCA
A protein w/ 10 transmembrane 140kDa Transports Ca++ from cytosol to extracellular Maintains 10,000-fold gradient across PM Uses ATP to pump Ca+ uphill
PMCA
Stimulated by the Ca+ binding protein calmodulin (CaM)
PMCA
Zaidi research
Structure of PMCA
Active site of CaM
ATP binding site
PMCA ex:
[CaM] calmodulin
Ca++ transport channel open when active or inactive?
Active
10 transmembrane domains 110 kDa Transports Ca+ from cytosol to ER 80% of SR membrane protein Uses ATP Plays role in relaxation of contracted muscle
SERCA
Key characteristic of Ca+ pumps SERCA and PMCA
Conformational change
Human genome has 150 genes
Have common architecture
Multi-drug resistance protein/ P glycoprotein
Pump wide range of small molecules out of cells
Uses ATP as energy source
ABC transporters
ATP binding domain is typically
In cytosol
Does ABC transporters have conformational change?
Yes
What happens to ATP affinity when substrate binds?
Increases
Active transport mediators not directly driven by ATP
Thermodynamically unfavorable flow of one species of ion against gradient coupled to favorable flow of another species down gradient
Secondary transporters
Ions move in opposite direction
Antiporters
Ions move in same direction
Symporters
Ions can move in both directions, depending upon the [ ]
Uniporter
Ex of antiporter
Sodium calcium exchanger
Ex of symporter
Lactose permease
Ex of uniporter
Mitochondrial Ca+ transporter
Uses a proton gradient generated by oxidation of fuel molecules to drive lactose and other sugars against [ ] gradient
Is a symporter
Lactose permease
Steps of lactose permease:
1-H+ out 2-lactose out 3-EVERSION 4-lactose in 5- H+ in 6-EVERSION
Polytopic membrane proteins are often:
Transporters
What 2nd structure are proteins that make up polytopic transport proteins in membrane
A helices
Sodium pump _____ and K+ pumps in ______
Out; in
uses ATP to change conformation for action to occur
Ptype atpase
If + ∆G what type of transport
Active transport
If -∆G what transport:
Passive: simple or facilitated diffusion
Why is P type called P type ATPase?
P=phosphate covalently bonded to protein during process that req’s energy.
Ex: SERCA Na+/K+ pump / PMCA
Where does (Pi) phosphate bind on P type ATPase?
Aspartate residue
Inhibit the dephosphorylation of E2P state of the Na+/K+ pump
Digitalis
ATP binds to this point________ causing the active for of PMCA
btw 4 and 5 transmembrane domains
Abc transporter
MRSA
What position SERCA bind a phosphate thus activating its Ca++ transport capabilities
Asp 351