Membranes and Transport Flashcards
Physiological Role of Membranes
- physical ______ _______ around cells and organelles
- gives cell its _______ ______
- separates the _______ environment from the ______ medium
- ____________ of organelles
- aids in _____ recognition
- provides _________ site for cytoskeletal elements
- ________ site for hormones and enzymes
- maintain ________ potential (membrane excitability)
- interlocking surfaces _____ cell together (tissue structure/gap junctions)
- _______ permeability of metabolites
- ______: exchange of material (nutrition, oxygen, waste, ions)
- protective barrier
- characteristic shape
- intracellular, external
- compartmentalization
- cell
- anchoring
- binding
- electrochemical
- binds
- selective
- transport
General Structure and Composition
- membranes are composed of ____, _____, and __________
- arranged in ______ bilayer
- ____ permeable (allows small molecules and lipid soluble molecules to diffuse through)
- primary components of membranes are ________
- lipids, proteins, carbohydrates
- asymmetric
- semi
- phospholipids
- main component of membranes
- amphiphatic: contain a hydrophilic head group and a hydrophobic tail group
phospholipids
Membrane Composition
- lipid bilayer serves are the _______ in which a variety of lipids and proteins are embedded, attached, or anchored
- carbohydrate molecules are ________ attached to some membrane lipids or proteins
- foundation
- covalently
What are the two types of phospholipids?
glycerophospholipids and sphingolipids
- phospholipid
- glycerol backbone with a phosphate and two fatty acids esterfied to backbone
- e.g. phosphatidylcholine, phosphatidylserine, phosphatidylinositol
glycerophospholipids
- phospholipid
- sphingosine backbone with a long chain fatty acid and phosphorylcholine
- sphingomyelin (most common SL present in outer leaflet)
sphingolipids
What are the 3 types of membrane lipids?
phospholipids, glycolipids, cholesterol
- membrane lipid
- sphingosine backbone with carbohydrate (oligosaccharide) residue(s)
- found in outer leaflet of lipid bilayer
glycolipids
- membrane lipid
- embedded in lipid bilayer
- steroid nucleus with hydroxyl group and hydrocarbon side chain
- the hydrocarbon chain interacts with hydrophobic tails of membrane lipids
cholesterol
What are the 3 types of membrane proteins?
intergral, peripheral, and lipid-anchored
- membrane protein
- firmly embedded in the membrane and stabilized by hydrophobic interactions with lipids
- polytopic membrane proteins (includes transporters, ion channels, and receptors
integral membrane proteins
- integral membrane proteins that span the entire lipid bilayer, weave in and out of the membrane several times and interact with both the internal and external environment
- include transporters, ion channels, and receptors that regulate the movement of molecules across membrane and receive and transmit signals from external environment of the cell
polytopic transmembrane proteins
- membrane protein
- loosely bound to membrane through electrostatic interactions with lipids or proteins
peripheral proteins
- membrane protein
- tethered to membranes via covalent attachment to a lipid
lipid-anchored proteins
- carbohydrate molecules are ______ attached to specific membrane lipids and proteins that face extracellular space
- outer sheet of some membranes covered with a carbohydrate shell called ______ due to presence of glycolipids and glycosylated proteins
covalently, glycocalyx
What are the 3 key functions of glycocalyx?
- protection: protects membrane components from mechanical injury or premature enzymatic degradation
- cell adhesion: makes more stable contacts with other cells, important during tissue formation and fertilization
- cell identification: allows body to differentiate between its own healthy cells from forge in, very important in red blood cells
Membrane Fluidity - proteins and lipids \_\_\_\_\_ and move \_\_\_\_\_\_ in membranes - gives it a fluid like quality - crucial for \_\_\_\_\_\_ allows proteins and lipids to undergo \_\_\_\_\_\_\_\_\_\_ changes and/or to move to specific areas within membrane to carry out \_\_\_\_\_\_ - factors that influence fluidity: A. temperature B. lipid composition C. cholesterol
- rotate, laterally
- function
- conformational, function
What are the 3 factors that influence membrane fluidity?
temperature, lipid composition, cholesterol
What is the temp at which membranes switch from fluid to rigid state?
melting temp (Tm)
Temperature
- below Tm membrane lipid molecules show ordered packing which makes membranes _____
- above Tm membranes are more _____
- Temp > Tm is optimal fluidity
- rigid
- fluid
Lipid Composition
- lipids that contain long, saturated fatty acids ______ membrane fluidity due to tight packing which reduces their mobility
- lipid with short, unsaturated fatty acid chains ______ membrane fluidity because the kinks in their fatty acid chains do not allow tight packing
- decrease
- increase
saturated lipids = ______ fluidity
unsaturated lipids = _______ fluidity
decrease, increase
Cholesterol in Membrane
- can either increase or decrease fluidity
- if membrane is too rigid (high sat fats or temp below Tm), cholesterol intercalates into membrane and _______ fluidity by preventing close packing of the lipids
- if membrane is fluid (high unsat fats), cholesterol ______ fluidity by fitting in gaps created by kinks in the tail lipids
- ______ large changes in fluidity caused by temperature
- increases
- stabilizes
- reduces
cholesterol in rigid membrane = ______ fluidity
cholesterol in fluid membrane = ______ fluidity
increase, decrease
Membrane Transport
- plasma membrane is ____-_______
- permeable to ______ molecules, move easily via diffusion (e.g. steroids)
- impermeable to ________ molecules, need a specific transport mechanism
- integral membrane proteins embedded in membrane function as ______ proteins
- membranes ______ the flow of biomolecules into and out of cells
- control biochemical properties of cell
- semi-permeable
- lipophilic
- hydrophilic/polar
- transporter
- regulate
In terms of Na+, K+, and Cl-, what are the conc intra and extracellularly
Na+ and Cl- higher extracellularly,
K+ higher intracellularly
- energy-independent movement of molecules down a gradient (higher conc to lower conc)
- two types: simple diffusion and facilitated diffusion
passive transport
- passive transport
- occurs unaided
- molecules that are small, non-polar and uncharged polar diffuse freely across the membrane
- steeper the gradient, faster the diffusion
simple diffusion
- passive transport
- needs the assistance of transmembrane proteins
- molecules that are large and charged are unable to cross the membrane
- need a facilitator (proteins that help movement)
- proteins function as ion channels or transporters
- greatly increase rate of transport
facilitated diffusion
- pores or gates in membrane which allow charged and polar molecules (e.g. ions and water) to move across membranes down their concentration gradient
- open/close in response to stimuli
- channels high throughout (transport millions of molecules per second)
ion channels
- ion channel
- binding of ligand (e.g. neurotransmitter or hormone) to ion channel causes conformation changes in the protein
- facilitate opening of the channel, allowing rapid transport of ions across membrane
- ions move down concentration gradient
- dissociation of ligand closes the channel
- example: glutamate receptor: antagonist of glutamate receptor used to treat Alzheimer’s disease (Mimantine/Namenda)
ligand-gated ion channels
- ion channel
- open/close in response to changes in membrane potential
- electrical voltage across the lipid bilayer created by large excess of negative charge inside the cell
- depolarization (increase in membrane potential due to influx of positively charged ions) triggers the opening of these channels permitting specific ions to cross the bilayer down their conc gradient
- found in excitable cells, such as neurons
- example: sodium channel
voltage-gated ion channels
- puffer fish example: has toxin called tetradotoxin which binds to sodium channel and inhibits neurotransmission
- topical anesthetics: block sodium channel, inhibit nt, used in clinic to block pain
consequences of blocking ion channels
- membrane transport
- energy-dependent, protein-assisted movement of molecules against their concentration gradient
- mediated by integral membrane proteins (polytopic transmembrane protein transporters)
- bind to a specific molecule on one side of membrane and release it on the other side
- 2 types: primary (uses ATP directly) and secondary (coupled to primary transport)
active transport
- active membrane transport
- uses ATP directly
- P type ATPases: ATP hydrolyzed, protein gets phosphorylated
- ABC transporters: ATP hydrolyzed, protein not phosphorylated
primary active transport
- active membrane transport
- does not use ATP, uses energy stored in concentration gradient
- thermodynamically unfavorable flow of one species of ion against a gradient coupled to a favorable flow of another species down a gradient
secondary active transport
- monosaccharides derived from digestion need to be transported from intestinal ____, across the ______ into the _____ ______
- this transport process is facilitated by ______ diffusion (passive) and ______ transport
- lumen, enterocyte, blood stream
- facilitated, active
Transport Mechanisms in Uptake of Dietary Monosaccharides
- D-_____ and D-______ enter intestinal ________ cells from lumen along with ___ by _______ active transport mediated by sodium-glucose transporter 1 (_____) in apical surface
- ______ transported only by ______ diffusion down its concentration gradient using GLUT5 transporter on _____ side and _____ transporters on _____ side of enterocyte
- ___ transported in by SGLT1 is delivered to the blood stream using a ______ active transport process mediated by _________ in the basolateral membrane
- glucose, galactose, epithelial, Na+, secondary, SGLT1
- fructose, facilitated, apical, GLUT2, basal
- Na+, primary, Na+/K+-ATPase
- caused by deficiency in the activity of an enzyme called acid sphingomyelinase (A-SMase)
- A-SMase is a lysosomal enzyme which breaks down sphingomyelin (SM) into ceramide and phosphorylcholine
- defective A-SMase leads to accumulation of SM in lysosomes of liver, spleen, CNS, and bone marrow
- leads to: enlargement of liver and spleen
- causes neurological damage
- hallmark “cherry red spot” in the eye
- fatality: type A is 85% by 18 months of age
Niemann-Pick disease
- in healthy cells, phosphatidylserine (PS) found in inner leaflet of bilayer
- during apoptosis, PS is transferred to outer leaflet of bilayer
- serves as tag/label for dying cells to be recognized and removed by phagocytes
phosphatidylserine as a marker for apotosis
- type of hemolytic anemia
- associated w/ beta lipoproteinemia and advanced alcoholic cirrhosis
- chronic liver dysfunction impairs cholesterol metabolism in liver, results in excess free cholesterol
- elevated levels of cholesterol bound to RBC membrane
- decrease fluidity and flexibility of membrane
- creates rough, thorny projections on RBC’s, acanthocytes
- cause RBC’s to lyse as they pass through capillaries of spleen = reduced RBC survival
- prognosis is poor, median survival is a few months
- liver transplantation represents the only potentially curative option
spur cell anemia
- autosomal recessive disorder
- caused by defect in transporter responsible for uptake of dimeric amino acid, Cystine, and dibasic amino acids such as Arginine, Lysine, and Ornithine
- results in formation of cystine stones in kidney
- patients present with renal cholic (abd pain that comes in waves and is linked to kidney stones)
cystinuria
- autosomal recessive disorder
- caused by defect in a transporter for non-polar or neutral amino acids (e.g. alanine, valine, threonine, leucine, tryptophan, etc.)
- primary in kidneys and intestine
- deficiency in tryptophan (precursor for serotonin, melatonin, and niacin) affects health
- manifests in infancy as failure to thrive
- clinical findings: intermittent cerebellar ataxia (lack of muscle coordination), nystagmus (rapid and repetitive eye movement), tremor, photo dermatitis, and photosensitivity
- triggered by sunlight, fever, drugs, or stress
- period of poor nutrition almost always precedes and attack
Hartnup disease (pellagra-like dermatosis)
Cardiotonic Drugs
- cardiac _____ such as ouabain and ______ act as potent cardio tonic (contraction-inducing) drugs
- _____ the Na+/K+-ATPase in cardiac myocytes
- leads to ______ in intracellular Na+
- this impairs activity of the secondary transporter _____ ______ ______ (NCX) which is coupled to the Na/K-ATPase
- impairment of NCX leads to secondary _______ in ___ in sarco-endoplasmic reticulum, which in turn ______ the ________ force of cardiac ______
- therapeutic use: congestive heart failure, atrial fibrillation, dysrhythmias
- historically: plant extracts containing cardiac glycosides (foxglove, oleander, lily of the valley) have been used as arrow coatings, homicidal/suicidal aids, rat poisons, diuretics, and emetics
- purified extracts/synthetic analogues now used for tx of CHF and arrhythmias
- glycosides, digoxin
- inhibits
- increase
- sodium calcium exchanger
- increase, Ca+, increases, contractile, myocytes
- autosomal recessive disorder
- mutation in _____ ______ transmembrane conductance regulator (CFTR) gene
- defective CFTR protein is misfiled and does not leave ER after translation
- CFTR protein is a chloride ion channel that mediates active transport of Cl- from inside to outside cells in airways and sweat ducts
- uses energy of ATP hydrolysis
- defective CFTR causes buildup of Cl- inside airway epithelial cells
- compensated by increase in Na+, which makes NaCl (salt)
- water flows into airway cells to compensate for increased salinity, decreasing the water content of surface mucous layer
- this leads to thicker mucous and leaves airways susceptible to bacterial infections
cystic fibrosis
red blood cells have _____ on their surface, which are different ________ attached to proteins (______) and lipids (________) on RBC membrane
antigens, carbohydrates, glycoproteins, glycolipids
Why is important to cross-match blood types when performing a blood transfusion?
Because plasma of recipient may contain antibodies to one or more of the ABO and Rh antigens. Incompatible transfusion could result in acute hemolysis, renal failure, and shock.
- RBC antigens that are applied to D antigen
- inherited in an autosomal dominant fashion
- (+) individuals express D antigen, (-) individuals do not
Rh factor
- disease in which there is incompatibility between blood of mother and fetus
- when mom is Rh- and fetus is Rh+, the mom produces antibodies during pregnancy which can cross the placenta and attack fetus
- risk is greater in subsequent pregnancies
hemolytic disease in newborns (erythroblastosis fetalis)