Biological Membranes Flashcards
What is the purpose of integral transmembrane proteins?
The control the access of inorganic ions, vitamins and nutrients. Also exit of drugs and the exit of waste products.
What is the concentration levels of K,Na,and Ca in the cytoplasm?
The concentration of K=140, Na= 10 and Ca= 10^-4 mmol/L.
What is the concentration levels of K,Na,and Ca outside the cell?
The concentration of K=5, Na= 145 and Ca= 1-2 mmol/L.
what is the driving force (indirectly or directly) for transport of ions?
ATP
Small non polar and uncharged molecules pas through the membrane via?
simple difussion
The term downhill refers to movement of?
Molecules moving along the concentration gradient from high to low concentration
The interior of the phospolipid bilayer is?
Hydrophobic
The term partition coeficcient refers to?
Transport of molecules between oil and water
what kind of proteins control movement of water across the membrane ?
Channel proteins.
what is the name of the channel protein gene in water?
Aquaporin -2
Neprogenic diabetes insipidus is characterized by?
excessive urination. Without the hyperglycemia characteristics of diabetes mellitus.
mutation in which gene gives as result NEPHROGENIC DIABITIS INSIPIDUS?
Aquaporin-2
Antibiotics act as what kind of carrier?
Ionophores
Ionophores carriers are?
Carriers that are bound to an ion to pass across the membrane. only down their electrochemical gradient.
Mention a typical example of mobile ion carrier?
VALINOMYCIN
The carrier type NIGERICIN and MONENSIN exchange what kind of ions respectively?
K, Na AND H
IONOMYCIN and A23187 are what kind of ionophores?
Ca^2+ Only
B-helical Gramicidin A makes transmembrane channel that allows movement of?
monovalent cations ( H, Na and K)
Polyene antibiotics AMPHOTERICIN B and NYSTATIN are active againts?
YEAST. Use for treatment of topical infections of fungal origin
What are other names for transporters?
Porters, permeases, translocases or carrier proteins
what are the two transport system mechanism?
facilitated diffusion and active transport
what is facilitated diffusion?
Movement down concentration gradient and does not required energy
what is active transport?
Movement uphill, against their concentration gradient
T/F The rate of facilitated diffusion is lower than that of simple diffusion ?
FALSE
Which type fo diffusion has a maximun transport rate Tmax?
facilitated diffusion
which equation can be use to describe facilitated diffusion kinetics?
Michaelis-Menten and Lineweaver-Burk type equations
rate is slower and directly proportional to substrate concentration in ?
SIMPLE DIFFUSION
Clinical: child with polyuria,failure to thirve and an episode of severe dehydration.
Lab: Urine dipstick shows= Glucosuria and Proteinuria
Bichemical analysis: Aminoaciduria and phosphaturia
The possible diagnosis is ?
INFANTILE CYSTINOSIS
- accumulation of cystine in lysosomes , due to defect in lysosomal transport protein
Clinical :
Symptoms: Pellagra-like skin changes on face ,neck,forearms and dorsal aspects of hands and legs
Skin: scaly , rough and hyperpigmented
Complains: Headaches and wekness
urinalysis: hyperaminoaciduria of neutral monoamino-monocarboxylic acids( alanine,serine,threonine,asparagine,glutamine,valine,leucine,
isoleucine,
phenylalanine,tyrosine,tryptophan,histidine and citrulline)
The possible diagnosis is?
HARTNUP DISEASE
- Aminoacids share a common transporter only expressed in luminal border of epithelial cells of renal tubules and intestinal epithelium.
- pellagra dermatitis and neurological involvement : nutritional niacin deficiency
- reduced tryptophan intake results in reduced nicotinamide production
what is the treatment for cystinosis?
Intake of cysteamine to increase transport of cystine
HARNUP DISEASE is treated with?
Oral nicotinamide and application sunblock in affected areas
Glucose transporters difussed via ?
FACILITATED DIFFUSION
Glucose transporters are uniport, symport or antiport?
UNIPORT
Substrates for GLUT1 are?
Glucose, Galactose and mannose
Major sites of expression for GLUT1 ?
Erythrocytes , blood tissue barriers(ubiquitous)
Substrates for GLUT2 are?
glucose and fructose
Substrates for GLUT3 are?
glucose
Substrates for GLUT4 are?
glucose
Substrates for GLUT5 are?
fructose
Major sites of expression for GLUT2 ?
liver,pancreatic islets and intestines
Major sites of expression for GLUT3?
brain, testis
Major sites of expression for GLUT4 ?
muscle,fat,heart
Major sites of expression for GLUT5?
intestine(primarily),testis and kidneys
Major sites of expression for GLUT6?
spleen. leukocytes and brain
Major sites of expression for GLUT7 ?
small intestine, colon
Major sites of expression for GLUT8 ?
testis
Major sites of expression for GLUT9 ?
liver.kidney
Major sites of expression for GLUT10 ?
heart,lung,brain,liver,muscle,pancreas,kidney
Major sites of expression for GLUT11 ?
heart,skeletal muscle,kidney
Major sites of expression for GLUT12?
skeletal muscle,heart,prostate, small intestine
Major sites of expression for GLUT13 ?
HMIT, primarily expressed in brain
Major sites of expression for GLUT1 4?
testis
what is voltage or ligand gating?
Ability of transporter to open and close by conformational changes induced for volatge changes or ligand binding.
Clinical:
-Infant
-recurring seizures
-CSF glucose low
CSF lactose low 0.3-0.4 mmol/L;3-4mg/dL(normal values <2.2 mmol/L; <20 mg/dL)
-Ratio ranging from 0.19-0.33(normal value is 0.65)
Possible condition is?
Defective glucose transport across the blood brain barrier as a cause of seizures and developmental delay
what are the potential causes for low CSF glucose concentrations?
Bacterial meningitis, subarachnoid hemorrhage and hypoglycemia.
CSF LACTATE values are usually found in what conditions?
Bacterial meningitis, subarachnoid hemorrhage
Defective glucose transport across the blood brain barrier can be treated with?
KETOGENIC DIET (high fats, low protein , low carbohydrate) - Brain can use ketone bodies as oxidizable fuel sources and the entry is not glucose transporter system dependent.
GAP JUNCTIONS are located where?
betwen endothelial,muscle and neuronal cells cluster of small pores
how are pores form?
2 cylinders of six CONNEXIN subunits in the plasma membrane join each other
what causes deafness and Charcot Marie-Tooth disease?
mutations in genes Connexin 26 and Connexin 32
larger proteins and nucleic acids enter and leave nucleus via?
Nuclear Pores
Primary active transport systems use ?
ATP
Secundary active transport systems use?
Electrochemical gradient of Na or H ions
pump ATpases are classified into?
F-ATpase(coupling factor), V-ATpase(vacuolar), P-ATpase(phosphorylation), ABC( ATP-Binding cassette) transporter.
F-ATpases are located in?
mitochondrial,chloroplast and bacterial membranes
substrate for F-ATpases are?
H ions
function of ATpases is?
ATP synthesis driven by electrochemical gradeint of H ions
ATP is transported to the cytoplasm via?
ATP-ADP TRANSLOCASE in the mitochondrial inner membrane
ATP-ADP TRANSLOCASE is an _______ system?
ANTIPORT
what is the location of V-type(vacuolar) ATPase?
lysosomes,endosomes, and secretory granules and plasma membranes(ruffled border of osteoclast,kidney ephitelial cell)
defects in V-ATpase results in ?
OSTEOPETROSIS
- increased bone density
mutation in ATPase collecting ducts on the kidney causes?
Renal tubular acidosis
what are the functions of V-ATPases
activation of lysosomal enzymes, accumulation of neurotransmitters, turnover of bone, acidification of urine
What are the members of the P-ATPase(phosphorylation)
Na/K ATPase, H/K ATPase, Ca^2+ ATPase, Cu^2+ ATPase
Mutations of ATPase genes cause?
BRODY CARDIOMYOPATHY(Ca^2+ ATPase)
FAMILIAL HEMIPLEGIC MIGRAINE TYPE 2 (Na/K ATPase)
Menke’s and wilsons diseases ( Cu^2+ ATPases)
location of Na/K ATPase?
plasma membranes(ubiquitous, but abundant in kidney and heart)
function of Na/K ATPase?
Generation of electrochemical gradient of Na and K
location of H/K-ATPase?
stomach(parietal cell in gastric gland)
function of H/KATPase?
acidification of stomcah lumen
Location CA2+ ATPase?
sarcoplasmic reticulum and endoplasmic reticulum
function of Ca2+?
Ca2+ sequestration into sarcoplasmic(endoplasmic) reticulum
location of #2 Ca2+ ATPase?
plasma membrane
function of #2 Ca2+ ATPase?
Ca2+ excretion to outside of the cell
location of Cu2+ ATPase?
plasma membrane and cytoplasmic vesicles
Function of Cu2+ATPase?
Cu2+ absorption from intestine and excretion from liver
what are the categories for the ABC(ATP-binding cassette) transporter?
- P-glycoprotein
- MRP
- CFTR
- TAP
location of P-glycoprotein?
plasma membrane
function of P-glycoprotein
excretion of harmful substances, multidrug resistance for anticancer drugs
location MRP(MULTI DRUG RESISTANCE ASSOCIATED PROTEIN)
plasma membrane
function of MRP
detoxification , multidrug resistance
location of CFTR(CYSTIC FIBROSIS TRANSMEMBRANE CONDUCTANCE REGULATOR)
plasma membrane
Function of CFTR
c-AMP dependent chloride channel, regulation of other channels
Location of TAP (TRANSPORTER ASSOCIATED WITH ANTIGEN PROCESSING)
Endoplasmic reticulum
function of TAP
presentation of peptides for immune response
examples of secundary active transport?
uniport(monoport),symport(cotransport),antiport(countertransport)
why copper is toxict in excess?
binds to proteins and nucleic acids, enhances generation of free radicals and catalyzes oxidation of lipids and proteins in membranes
which disease is characterized by failure to incorporate copper into ceruloplasmin in the liver and failure to excrete copper from the liver , resulting in toxic accumulation of copper in the liver and also in the kidney, brain and cornea
WILSON’S DISEASE
Treatment for WILSON’S DISEASE?
chalating agents
- PENICILLAMINE
- oral ZINC
in which disease copper enters the intestinal cells, but is not transported further, resulting in severe copper deficiency ?
MENKES DISEASE
Treatment for MENKES DISEASE?
subcutaneous administration of cooper histidine complex
what are the cause of Cystic fibrosis?
mutations of the CFTR gene. ATP binding to CFTR is required for channel opening , the lack of this activity in the ephitelia of CF patients affects both ion and water secretion
the following diseases are caused by defects in which transporter?
- tangier , stargardt,progressice intrahepatic cholestasis, dubin johson syndrome, pseudoxanthomaelasticum,familial persisnte hyperinsulinemic hypoglycemia of infancy (PHHI),adrenoleukodystrophy, zellweger syndrome, sitosterolemia and cystic fribrosis
ABC TRANSPORTERS
what is the most common potentially lethal autosomal recessive disease of caucasian populations?
CYSTIC FIBROSIS
VOLTAGE DEPENDENT Ca2+ CHANNELS(VDCCs)
change the conformation fo t tubules in skeletal muscle in response to membrane depolarization and directly activate a Ca2+ release channel in the sarcoplasmic reticulum membrane
what drives the uptake of glucose into intestinal and renal epithelial cells?
Na/K-ATPase
what transport glucose into the intestinal epithelial cells?
AN Na+ COUPLED GLUCOSE SYMPORTER (SGLT1)
What facilitates the downhill movement of glucose into the portal circulation?
GLUT 2
function of SODIUM GLUCOSE TRANSPORTER 2(SGLT2)?
glucose re absorption into the renal proximal tubular epithelial cells.
what is use for the treatment of hypertension?
DHP
Dihydropyridine
nifedipine
* calcium channel blocker
what is RYANODINE ?
potent inhibitor of the Ca++ channel in the sarcoplasmic reticulum.
which are the common Ca2+ channel blockers that inhibits VDCCs?
phenylalkylamine(verapamil), benzothiazepine(diltiazem) and dihydropyridine(DHP,nifedipine)
inhibition of Na+ channels represses?
transmission of the depolarization signal
what is used for treatment of congestive heart failure?
cardiac glycosides
- OUABAIN
- DIGOXIN
alfa-bungarotoxin and tetrodotoxin are?
snake vemon and puffer fish
alfa-bungarotoxin and tetrodotoxin inhibits?
voltage dependent Na+ channels
lidocaine is used for ?
Na+ channel blocker , local anesthetic and antiarrythmic drug
P-ATPase in gastric parietal cells maintains?
the low PH of the stomach
the lumen in the stomach is highly acidic due to ?
Presence of a proton pump H/K-ATPase ,PATPase.
why is it called an H+/K+-ATPase?
Because the pump antiports two cytoplasmic protons and two extracellular potassium ions, coupled with hydrolysis of a molecule of ATP
PHLORIZIN inhibits?
SGLT1
PHLORETIN inhibits?
SGLT2
what causes glucose/galactose malabsorption?
defect on SGLT1
The kidney is a major site for regulation of ?
Na+ homeostasis.
-several transport systems participate in Na+ handling in the kidney tubules.
most of Na+ reabsorption in the tubules occurs in the?
PROXIMAL SEGMENTS
Na+ reabsorption in the distal nephron is sensitive to?
STEROID HORMONE ALDOSTERONE
Where’s the gastric pump localized?
intracellular vesicles in the resting state.
histamine and gastrin are in charge of ?
inducing fusion of the vesicles with the plasma membrane
in gastric juice acidification the counter ion CL- is secreted through a Cl- channel producing __________ in the lumen.
HYDROCHLORIC ACID(HCl: gastric acid)
The Na+/H antiporter (NHE3) mediates ________
entry of Na+ in the proximal tubule
Furosemide-sensitive Na+-K+-2Cl-(symporter)(NKCC2) and Thiazide-sensitive Na+-Cl-(cotransporter)(NCCT) where are localizated?
Thick ascending loop of Henle and distal convoluted tubules
Amiloridesensitive epithelial Na+ channel(ENaC) is expressed where?
Aldosterone-sensitive distal nephron
ionic balance of epithelial cells is regulated by??
Renal outer medullary K+channel(ROMK) and the Cl- channel ( ClC)
What plays a central role in the regulation of circulating volume, extracellular fluid osmolality and blood pressure?
The RENIN-ANGIOTENSIN-ALDOSTERONE SYSTEM
Where is RENIN produced?
in the juxtaglomerular apparatus of the kidney
Angiotensinogen is converted into?
Angiotensin I
Angiotensin I is converted into?
Angiotensin II
Angiotensin converting enzyme (ACE) is in charge of ?
converting Angiotensin I into Angiotensin II
What promotes the release of aldosterone?
Angiotensin II
what enzyme promotes the renal Na+ and water retention and elevated blood pressure by increasing Na+ reabsorption in the cortical collecting duct ?
ALDOSTERONE
What promotes elevations in blood pressure by direct vasoconstriction and increasing Na+ reabsoprtion in the proximal tubule?
ANGIOTENSIN II
OMEPRAZOLE covalently modifies?
Cysteine residues located in the extracytoplasmic domain of the Alfa-subunit and inhibits the proton pump.
