Mcb Week 2

Front 1

Glycoproteins

Back 1

-proteins that contain covalently attached carbohydrate
-usually found in extracellular spaces or on the non-cytosolic side of the membrane system

Front 2

Functions of Carbohydrates in Glycoproteins

Back 2

-recognition
-physical properties
-stabilize proteins
-modulate activity of proteins
-protein quality control
-store energy

Front 3

Carbohydrates added to proteins...

Back 3

-usually added to proteins in the endoplasmic reticulum or in the golgi
-consequently, carbohydrates always face away from the cytosol
-exception is small number of proteins that have a single NAcetyl-
glucosamine (GlcNAc) attached to a Ser or Thr

Front 4

sugar linkages

Back 4

1,2 or 1,3 or 1,4 or 1,6 are common linkages

Front 5

anomers

Back 5

sugars attached as either alpha or beta anomers (depend on position of sugar)

Front 6

sugars generally have...

Back 6

several -OH groups for the next sugar to attach to

Front 7

O-linked

Back 7

carbohydrates attached to Ser or Thr

Front 8

N-linked

Back 8

carbohydrates attached to Asn

Front 9

sugar attachment

Back 9

-attached one at a time
-dependent on presence of specific glycosyltransferase enzymes
-dependent on proper substrate and necessary activated sugars

Front 10

activated sugars

Back 10

usually a sugar with a
nucleoside diphosphate or a nucleoside phosphate

Front 11

Glycoprotein Synthesis

Back 11

-sequential (one element cannot be added until the one before it is added)
-not templated --> just requires appropriate precursors & enzymes to be present --> can result in small variations
-not contrained to being linear (many are branched)

Front 12

Micoheterogeneity

Back 12

-small variation due to non-templated synthesis of glycoprotein chains

Front 13

N-linked Glycoproteins

Back 13

-have 8-25 residues
-linked via N-glycosidic bond to Asn residue
-carbohyrdates contain a conserved core

Front 14

high mannose

Back 14

-one class of N-linked glycoproteins
-because it has mannosyl-mannose substituents on
the core structure

Front 15

complex

Back 15

-one form of N-linked glycoproteins
-because substituents on the core consist of a short chain
composed of multiple sugar types, e.g., Sia → gal→ glcnac → core

Front 16

hybrid glycoproteins

Back 16

-contain both high-mannose and complex Nlinked
carbohydrates

Front 17

carbohydrate chain (N-linked carbohydrates)

Back 17

-first formed on a lipid carrier
(dolichol) located in the membrane of the ER

Front 18

dolichol

Back 18

-long and very hydrophobic
-its 22 five-carbon units can span the thickness of a lipid bilayer more than three times, so that the attached
oligosaccharide is firmly anchored in the membrane

Front 19

first sugar linked to dolichol...

Back 19

-by a pyrophosphate bridge
-this high-energy bond activates the
oligosaccharide for its eventual transfer from the lipid to the protein.

Front 20

oligosaccharide synthesis (N-linked)

Back 20

-starts on the cytosolic side of the ER membrane
-continues on the lumenal face after lipid intermediate is
flipped across the bilayer by a transporter protein

Front 21

dolichol-P glucose
and dolichol-P-mannose

Back 21

all glycosol transfer reactions on the lumenal side of the ER involve transfers from these lipid-linked monosaccharides

Front 22

tunicamycin

Back 22

-antibiotic that inhibits the first
reaction in the pathway of forming an N-linked oligiosaccharide

Front 23

removal of sugars from glycoproteins

Back 23

-carbohydrates processed by enzymes that remove some sugars and add others
-removal of sugars generally takes place in the ER or golgi

Front 24

glycoprotein processing pathway

Back 24

-highly ordered
-each step dependent on one before it

Front 25

endo-H

Back 25

-used to distinguish complex from high-mannose oligosaccharides
-does not occur naturally in the body (just a tool used to study glycoproteins)

Front 26

role of N-linked glycosylation in ER protein folding

Back 26

-once protein is completely synthesized in the lumen, calnexin (a chaperone) recongizes terminal glucose & binds to it to hekp it fold properly

Front 27

glucosidase

Back 27

-cleaves terminal glucose from protein & releases protein from calnexin

Front 28

glycosol transferase

Back 28

-checks to make sure protein in folded properly
-if not it attaches a new glucose to renew its affinity for calnexin and has it repeat the folding process

Front 29

Lysosome Targeting

Back 29

Review Pathway (Lecture 4 Notes - Page 11)

Front 30

lysosome

Back 30

organelles that contain enzymes to break down certain structures

Front 31

O-linked glycoproteins

Back 31

-carbohydrates are attached to side chain –OH of
Ser, Thr, or hydroxy-Lys
-Glycosylation takes place in the Golgi
-the carbohydrates may be quite diverse.

Front 32

O-linked sugar chains

Back 32

-usually < 15 sugars
-synthesized by a one-by-one addition of sugars

Front 33

N-acetylgalactosaminyl
transferase

Back 33

-first enzyme involved for
secreted and extracellular glycoproteins in O-linked glycolysis

Front 34

intercellular glycoproteins (o-linked)

Back 34

the sugar attached to Ser or Thr is usually N-acetyl-
glucosamine (GlcNAc).

Front 35

mucins

Back 35

-group of o-linked glycoproteins
-carry short o-linked carbohydrate chains
-components of the mucus secretions associated with
many epithelia of the body
-serve a protective function

Front 36

proteoglycans

Back 36

-contain linear polysaccharides of the form (X-Y)n, where n > 20
-Y is usually uronic acid
-X is usually hexosamine

Front 37

glycoasaminoglycans (GAG's)

Back 37

-polysaccharide chains (typically 30+ sugars)
-usually attached to Ser
residues in the sequence of Ser-Gly of core proteins via a unique sugar sequence

Front 38

enzyme complex

Back 38

-there appears to be an enzyme complex that contains 2 transferases, which
act together to form the disaccharide repeating structure

Front 39

hyaluronate

Back 39

does not appear as a proteoglycan, only as a glycosaminoglycan

Front 40

C-terminal linked carbohydrates

Back 40

-A number of membrane proteins have been found to contain phosphatidyl
inositol linked through a carbohydrate chain to the carboxyl group on the C-terminal end of the protein

Front 41

GPI anchor

Back 41

attaches to proteins at C-terminus to anchor them to the membrane

Front 42

glycogen

Back 42

-exists as a homodimer
-core protein (glycogenin) --> able to attach up to 8 glusose molecules to itself
-typically attached alpha 1-4, but occasionally attached alpha 1-6
-catalyzes addition of glucose molecules to itself, from UDP-glucose to the –
OH group of a Tyr side chain.

Front 43

glycosidases

Back 43

These are enzymes that usually have specificity for the sugar residue which supplies the reducing group involved in a glycosidic bond

Front 44

exoglycosidase

Back 44

-by far the most common
-act on non-reducing ends of
carbohydrate chains
-e.g., sialidase is specific for terminal sialic acid residues

Front 45

endoglycosidase

Back 45

-can cleave interior linkages
-e.g., α-galactosidase is specific for the cleavage of α-linked galactosyl residues.

Front 46

Mass Spectroscopy

Back 46

useful tool for identifying molecules or hydrolysis products on the basis of molecular weight

Front 47

lectins

Back 47

-carbohydrate binding-proteins
-distinct from antibodies
-have specificity for specific carbohydrate structures

Front 48

non-enzymatic glycation

Back 48

-this is a bad thing
-happens when there is too much glucose in the blood (ex. uncontrolled diabetes)

Front 49

aldehyde function of sugars...

Back 49

reactive at neutral pH and will combine with free amino groups of Lys and free N-terminus of proteins

Front 50

ketoamine

Back 50

-result from reaction of aldehydes with free amino groups
-can also form advanced glycation endproducts (AGEs

Front 51

HbA1c

Back 51

-glycated hemoglobin
-level of HbA1c rises in diabetics with poorly controlled blood sugar
-HbA1c value reflects the average blood glucose concentration over the preceeding 1-3 months

Front 52

blood glucose

Back 52

-tells you the current blood glucose concentration
-while HbA1c give value reflects the average blood glucose concentration over the preceeding 1-3 months

Front 53

aldehydes & amines

Back 53

-react spontaneously in water to form structures called imines
-amadori rearrangement --> not reveraible

Front 54

amadori rearrangement

Back 54

-structure that occurs during non-enzymatic glycation
-usually in diabetics with uncontrolled blood sugar
-not reversible

Front 55

O antigen

Back 55

-usually everyone has it

Front 56

A antigen

Back 56

-People who have the A antigen have a gene which makes an N-acetyl-galactosaminyl transferase
-this transferase
adds N-acetyl-galactosamine to the O antigen

Front 57

B antigen

Back 57

-People who have the B antigen have a gene which makes a galactosyl transferase
-this adds galactose to the O
antigen.

Front 58

Bombay phenotype

Back 58

-lack the gene for the fucosyl transferase which is responsible for completing the O antigen
-mutation is in the enzyme
which processes glycoproteins

Front 59

fucosyl transferase

Back 59

-responsible for completing th O antigen
-referred to as the primary gene product

Front 60

antigenic glycoprotein

Back 60

referred to as the secondary gene product

Front 61

lipid bilayer

Back 61

-serves as a barrier for most small polar substances
-water, urea, & glycerol can diffuse across easily
-sugars & ionic substances (Na+, K+, Cl-, etc.) can not
-small molecules diffuse easier than larger ones

Front 62

diffusion

Back 62

-tendency of solute to move from areas of high to low concentration
-energetically favorable because of entropy (increases randomness)

Front 63

at equilibirum

Back 63

concentrations will be uniform throughout system

Front 64

rate of diffusion (3 factors)

Back 64

-size
-polarity
-concentration gradient

Front 65

size (diffusion)

Back 65

smaller molecules diffuse faster

Front 66

polarity (diffusion)

Back 66

-less polar (hydrophobic) molecules pass much more rapidly than polar molecules

Front 67

concentration gradien (diffusion)

Back 67

-flow goes from high concentration to low concentration

Front 68

water (diffusion)

Back 68

diffuses easily due to small size and lack of charge

Front 69

aquaporin

Back 69

-water channels which allow water to pass through membrane very rapidly

Front 70

regulate concentrations of ions

Back 70

it is very important for cells to be able to regulate concentrations of solutes, especially salts
-must regulate osmolarity to maintain their shape & integrity

Front 71

osmolarity

Back 71

solute concentration

Front 72

iso-osmotic

Back 72

same total solute concentration

Front 73

electric potential gradient

Back 73

-differences in charge on either side of the membrane
-inside of the cell is more negative than the outside in mammals (inside typically at -70 mV)
-movement of positive charge in and negative charge out is energetically favorable

Front 74

electric gradient + conc. gradient

Back 74

for some ions, we need to calculate the net force (elec. grad. + conc. grad.) to know which way an ion will go

Front 75

drug molecules

Back 75

1)have to move into bilayer
2)have to move into cytosol
-move by diffusion
-need a balance between being hydrophobic/hydrophilic to be an effective drug and reach target

Front 76

partition coefficient

Back 76

measure of overall hydrophobicity

Front 77

transport (carrier) proteins

Back 77

-facilitate movement of solute molecules across lipid bilayer
-have an affinity for specific solutes
-conformational change translocates the solute to the other side of the membrane

Front 78

energy for transport proteins

Back 78

may come from:
1)concentration gradients
2)electric potential
3)coupling to an energy source (ex. ATP)

Front 79

Ion Channels

Back 79

regulated/gated channels that let ions pass through
-control pH
-regulate membrane potential
-etc.

Front 80

passive transport

Back 80

-goes in the direction of a concentration or electrical gradient
-requires no energy
-also known as facilitated diffusion
-reversible

Front 81

active transport

Back 81

-goes against the gradient
-requires energy
-often coupled with ATP hydrolysis
-usually not reversible

Front 82

uniport transport

Back 82

-single solute moving in one direction

Front 83

symport transport

Back 83

-2 solutes co-transported in same direction

Front 84

antiport transport

Back 84

-two solutes exchanged in opposite directions across the membrane

Front 85

passive uniport example

Back 85

glucose transport into red blood cells

Front 86

passive symport example

Back 86

glucose/Na+ transport into intestinal and kidney cells

Front 87

passive antiport example

Back 87

-Cl-/HCO3- exchange in red blood cells
-Na+/Ca++ exchange in cardiac cells

Front 88

active uniport example

Back 88

Ca++ ATPase

Front 89

active antiport example

Back 89

Na+/K+ ATPase

Front 90

passive transport enzymes

Back 90

are much like enzymes

Front 91

transport is subject to...

Back 91

competitive & non-competitive inhibition

Front 92

GLUT1

Back 92

-passive glucose uniport
-uses concentration gradient as source of energy
-very selective for D-glucose

Front 93

Michaelis-Menten Equation

Back 93

-rate of transport follows M-M equation
-

Front 94

normal blood glucose concentration

Back 94

about 5 mM

Front 95

intestinal epithelial cells

Back 95

-co-transport glucose with Na+ in order to get the sugar inside the cell which can come from an external environment that is higher or lower in glucose concentration (move glucose in even if it's against gradient)
-transport energy depends on conc. & elec. gradient of Na+ plus conc. gradient of glucose

Front 96

Na+ conc. and electrical gradient

Back 96

-is always favorable so transport of glucose into the cell is always favorable even if it is against conc. gradient
-2 Na+ molecules transported for each glucose molecule

Front 97

AE1

Back 97

-Anion Exchange Protein 1
-passive antiport protein that exchanges a Cl- for a HCO3-
-no net change in charge
-only depends on conc. gradients of both ions

Front 98

AE1: role in CO2 transport

Back 98

-systemic capillaries --> cells pick up CO2 which is converted to HCO3- via carbonic anhydrase --> HCO3- exchanged out for Cl-

-pulmonary capillaries: HCO3- taken in and Cl- goes out --> carbonic anhydrase turns HCO3- into H20 + CO2 --> CO2 released from cell

Front 99

Muscle Cells

Back 99

-keep intracellular Ca++ low by storing it in Sarcoplasmic Reticulum
-Ca++ released during action potential for use during contractions
-Ca++ ATPase moves Ca++ back into SR against gradient via ATP hydrolysis
-2 Ca++ moved per ATP (also requires Mg++)

Front 100

Na+/K+ gradient

Back 100

Na+/K+ gradients maintained by Na+/K+ exchanger which uses ATP hydrolysis to pump ions against their gradients
-3 Na+ out / 2 K+ in

Front 101

Na+/K+ ATPase

Back 101

consumes about 1/3 of a cells energy to maintain gradient

Front 102

gated pores

Back 102

-formed by ion channels
-have maximal velocity/conductance
-movement always goes in direction of gradient

Front 103

voltage gated ion channel

Back 103

opened/closed by changes in membrane potential

Front 104

ligand gated ion channel

Back 104

opened/closed by binding of ligands to receptor sites on the channel protein

Front 105

mechanical stress

Back 105

some ion channels are gated in response to sensory stimuli

Front 106

self regulating ion channels

Back 106

some channels close on their own after being open for a certain period of time

Front 107

selectivity (charge)

Back 107

-having a negativly charged side chains lining channel attract positive ions and repel negative ions

Front 108

selectivity (size)

Back 108

-some pores limit transport to ions/molecules of a certain size

Front 109

selectivity (entropy)

Back 109

-K+ and Na+ are both stabilized by interactions with oxygen atoms of H2O
-Na+ is smaller an can only interact with 2 oxygens while K+ can interact with 4
-K+ is therefore more favorable to pass through membrane

Front 110

calcium channel

Back 110

extremely selective

Front 111

voltage gated sodium channel

Back 111

-exist in 3 forms: closed, open, and inactivated

Front 112

closed sodium channel

Back 112

-when a cell is resting (-70 mV) the sodium channel is closed, but voltage sensitive

Front 113

open sodium channel

Back 113

-when the membrane potential move to about -50 mV (threshold potential) the channel opens

Front 114

self amplifying

Back 114

when sodium channels open do to reaching the threshold membrane, the membrane potential becomes even more positive --> opening more channels

Front 115

inactivated sodium channel

Back 115

-after a period of time, the channel closes and remains unaffected by voltage changes for a few milliseconds

Front 116

voltage gated ion channel segments

Back 116

-voltage gated ion channels typically have 24 transmembran helical segments
-sodium channels --> one long continuous protein
-postassium channels --> homotetramers (4 copies of a protein having 6 transmembrane segments)

Front 117

helix 4

Back 117

in voltage gated channels, helix 4, is the voltage sensor

Front 118

voltage gated postassium channels

Back 118

-helix 5 has outer loop
-helix 6 has inner loop
-selectivity loop in center is lined with oxygen

Front 119

channel inactivation

Back 119

-voltage gaetd channels are thought to inactivate by a "ball & chain" mechanism
-basically a ball connected to N-terminal domain plugs the channel

Front 120

REVIEW ACTION POTENTIAL

Back 120

Lecture 5 - Page 31

Front 121

axon

Back 121

long segment of neruons that propagated action potentials

Front 122

existance of inactive state

Back 122

allows signal to move in only one direction in neurons

Front 123

Nicotinic Acetylchloine Receptors

Back 123

-ligand gated sodium channels
-binding of Ach causes the channel to open
-channel has 5 subunits --> 2 alpha make up the acetylcholine binding sites
-lined with aspartate & glutatmate giving it a negative charge

Front 124

GABA & Glycine receptors

Back 124

-ligand gated chlorine channels in the CNS
-GABA & Glycine are inhibitory neurotransmitters
-lined with lysine & arginine giving it a positive charge

Front 125

aquaporins

Back 125

-proteins which form a tetrameric channel across cell membranes
-allow water to move faster than it could by diffusion
-targets of diuretics
-some allow urea & glycerol to pass as well as water

Front 126

ionophores

Back 126

-small hydrophobic molecules that mimic the action of ion channels
-act as channel formers & allow ions to pass in direction of conc. gradient or electrochemical gradient

Front 127

Valinomycin

Back 127

-cyclic polypeptide with hydrophobic exterior & hydrophilic interior (accomodates K+)
-functions as mobile ion carrier

Front 128

A23187

Back 128

-ion mobile carrier
-selective for divalent cations & readliy carries Ca++ into cells

Front 129

Gramicidin D

Back 129

-channel forming ionophore
-dimer forms cation channel that allows H+, K+, and Na+ to pass
-can be harmful to cells since it destroys concentration gradient

Front 130

Integrated Systems

Back 130

-some systems use a combination of channels & resources to carry out their function
-ex. transmission of nerve impulse to muscle, Glucose Uptake, Acid Secretion in Stomach --> Review Lecture 5 - Pages 38-41

Front 131

Eukaryotic Cells

Back 131

-compartmentalized
-10-20 times larger than prokaryotes

Front 132

membrane enclosed organelles

Back 132

-efficiently organize chemical reactions in functionally specialized spaces

Front 133

cytoplasm

Back 133

outside the nucleus within the plasma membrane

Front 134

cytosol

Back 134

-portion of the cytoplasm that is not enclosed in organelles
-makes up about 55% of the cells volume
-about 20% protein, 70% water

Front 135

protein sorting

Back 135

-proteins made in cytosol
-proteins use various mechanisms to get to target & fulfill function
-lots of proteins transported by vesicles, transmembrane transport, or gated transport

Front 136

specific sequence signals

Back 136

-newly synthesized proteins get to correct location due to signal peptides encoded in their primary sequence
-these signals are recognized by transmembrane translocators

Front 137

transmembrane translocators

Back 137

serve to deliver proteins to a particular destination

Front 138

3 transport mechanisms

Back 138

1)gated transport --> cytosol to nucleus
2)transmembrane transport --> cytosol to other membrane compartments
3)vesicular transport --> all other paths

Front 139

Zellweger Syndrom

Back 139

-autosomal recessive genetic disorder with many serious symptoms including:
-mental retardation
-enlarged liver, jaundice
-lack of muscle tone
-glaucoma
-can be caused by mutations in any of several genes associated with peroxisome biogenesis

Front 140

nucleus

Back 140

enclosed by a double membrane (nuclear envelope)

Front 141

nucleolus

Back 141

-has no membrane
-rich in RNA & protein
-source of rRNA synthesis & ribosome assembly

Front 142

nucleoplasm

Back 142

contents of nucleus - the nucleolus

Front 143

nuclear envelope

Back 143

-made up of 2 membranes

Front 144

outer nuclear membrane

Back 144

-continuous with endoplasmic reticulum

Front 145

nuclear pores

Back 145

-where inner & outer nuclear membranes connect
-large enough to permit DNA, RNA, folded proteins, & metabolites through
-about 3000-4000 in nucleus

Front 146

intermediate filaments

Back 146

2 networks of intermediate filaments support the nuclear evelope

Front 147

nuclear lamina

Back 147

forms a thin network just inside the nucleus

Front 148

nuclear localization signal

Back 148

-protein signal sequence specifically directed towards the nucleus
-import process requires GTP energy

Front 149

Ran

Back 149

-nuclear transport receptor
-example of importin protein

Front 150

nuclear pore fibrils

Back 150

extend from nuclear pores & form basket like structures

Front 151

signal sequence (location)

Back 151

-signals can be at N-terminus of protein, C-terminus of protein, or internal
-some protein can have an import & export function
-protein folding, activation, etc. can determine which sequence is expressed at a certain time

Front 152

ribosomal assembly

Back 152

-ribosomal subunits (synthesized in cytoplasm) enter the nucleus through nuclear pores & migrate to the nucleolus
-they combine with rRNA to make small & large subunits of ribosomes
-transported to the cytoplasm where they are assembled

Front 153

ribosome

Back 153

-machinery needed for translation
-it reads the sequence of mRNA and transfers it into amino acids

Front 154

Mitosis affect on nucleus

Back 154

during mitosis, the nuclear membrane and nucleolus are broken down

Front 155

mitochondria

Back 155

-membrane bound organelles present in virtually all eukaryotes
-occupy about 20% of cell volume
-produce ATP (cell's powerhouse)
-has two membranes
-has inner matrix
-may be simple or complex in shape

Front 156

mitochondial membrane

Back 156

-has outer membrane & inner membrane
-inner membrane involved in electron transport --> contains ATP synthase machinery
-outer membrane contains porins

Front 157

porins

Back 157

protein channels that allow water, salts, metabolites, and small proteins to pass freely into mitochondria

Front 158

inner mitochondrial membrane

Back 158

-involved in electron transport
-contains ATP syntahse machinery
-about 30% lipid & 70% protein

Front 159

cardiolipin

Back 159

-specialized lipid contained in inner membrane of mitochondria
-has 4 fatty acid chains & 2 phospholipids linked to a third glycerol molecule

Front 160

function of mitochondria

Back 160

-produce ATP by controlled oxidation of citric acid cycle intermediates
-electron transport through a series of complexes provides driving force for pumping of protons from mitochondrial matrix to intermembrane space
-creates concentration & electical gradient across inner membrane
-drive ATP systhase to turn ADP + phosphate into ATP

Front 161

mitochondrial DNA

Back 161

-makes up less than 1% of DNA in cell
-simple circular DNA (no histones)

Front 162

mitochondrial outsourcing

Back 162

-have DNA, RNA, and protein synthesis machinery in their matrix
-outsource most gene & protein synthesis to nucleus & free cytosolic ribosomes

Front 163

endosymbiont hypothesis

Back 163

-eukaryotes began as anaerobic organisms and then, when significant amounts of oxygen began to appear in the atmosphere, they
developed symbiotic relationships with prokaryotes that had electron transport capabilities necessary for aerobic metabolism
-some support comes from the fact that mitochondrial ribosomes are sensitive to many antibacterial antibiotics

Front 164

new mitochondria

Back 164

-arise from growth and division of existing mitochondria
-DNA must be replicated
-lipids & proteins must be synthesized & imported

Front 165

mitochondiral (inheiritance)

Back 165

-mitochondria are inheirited maternally

Front 166

mitochondrial disease inheiritance

Back 166

-non-Mendelian
-passed from mothers to both sons and daughters
-but in next generation, only daughter's offspring would be affected by disease

Front 167

cytosolic proteins designed for mitochondrion

Back 167

-have N-terminal signal sequence
-may bind to Hsp70 to prevent aggregation

Front 168

protease

Back 168

-cleaves signal sequence of of proteins once they are in the mitochondria
-the mature protein then folds

Front 169

Peroxisomes

Back 169

-organelles that carry out some oxidation reactions different from the oxidation reactions of the mitochondria
-carry out fatty acid oxidation --> one byproduct is hydrogen peroxide
-divide by fission to produce additional peroxisomes

Front 170

hydrogen peroxide

Back 170

-H2O2 is a byproducts of fatty acid oxidation performed by peroxisomes
-it is highly reactive & could cause cell damage
-peroxisomes prevent this damage using catalase --> converts H2O2 to water + oxygen

Front 171

catalase

Back 171

-enzyme used by peroxisomes to prevent cell damage
-converts hydrogen peroxide to water + oxygen

Front 172

plasmalogens

Back 172

ether lipids that are especially abundant in nervous system tissue

Front 173

peroxins

Back 173

-group of 23 proteins involved in importing proteins into peroxisomes
-peroxisome proteins do not need to be unfolded to reach peroxisome
-some peroxisomes targeted by a short 3 a.a. C-terminal signal sequence
-others targeted by a signal near N-terminal

Front 174

protein movement

Back 174

-proteins are moved from one membrane compartment to another by vesicular transport
-signals may be required for protein movement or for it to be retained in a cell

Front 175

endoplasmic reticulum membrane

Back 175

-a continuous lumenal compartment with rough & smooth regions
-about 50% of the total cell membrane
-selectively mediates the entry & exit of molecules into the ER lumen from the cytosol

Front 176

rough ER

Back 176

-ribosome associated
-actively involved in protein sysnthesis
-predominates in most cells

Front 177

smooth ER

Back 177

-ER lacking ribosomes
-cells involved in lipid biosynthesis contain a greater amount of smooth ER
-ex. cells in the adrenal cortex that synthesize steroid hormones from cholesterol & hepatocytes in liver

Front 178

Functions of the ER

Back 178

-Lipid synthesis, exchange & movement
-Detoxification of lipid soluble compounds
-Calcium sequestration
-Protein synthesis and processing

Front 179

phospholipid synthesis (location)

Back 179

-lipid synthesis takes place on the cytosolic side of the ER membrane
-after synthesis, a flippase (scramblase) equilibriates phospholipids on each side of the membrane by flipping phospholipids to the lumenal half

Front 180

cytochrome p450

Back 180

-family of enzymes involved in smooth ER detoxification reactions

Front 181

hepatocytes

Back 181

-in liver
-involved in detoxification
-have a significant amount of smooth ER

Front 182

smooth ER (functions)

Back 182

-modify a variety of lipid-soluble toxins including drugs, insecticides, petroleum products, carcinogens --> convert them to water soluble derivatives that can be secreted from the cell

Front 183

ER stores calcium

Back 183

-sequestering calcium in ER lumen maintains the Ca++ concentration in the cytosol
-Ca++ released into cytosol for physiological processes such as muscle contractions
-utilizes calcium channels, active calcium transporters, & calcium binding proteins in the ER lumen

Front 184

sarcoplasmic reticulum

Back 184

-specific term for ER in muscle
-specializes in storing & transporting calcium

Front 185

ER products

Back 185

-produces lipid droplets
-form peroxisomes

Front 186

rough ER (functions)

Back 186

-involved in the synthesis of secreted proteins & membrane proteins

Front 187

synthesis of all proteins (translation)

Back 187

synthesis of all proteins (translation) begins on ribosomes in the cytosol (excpet for mitochondrial protein synthesis which takes place in mitochondria)

Front 188

signal hypothesis

Back 188

-signal is recognized by membrane proteins
-a translocator provides a channel that allows protein to pass into ER lumen
-signal peptidase cleaves signal peptide

Front 189

signal recognition particle (SRP)

Back 189

-signal peptide is recognized on ribosome by SRP which binds nacent (newly forming) complex
-SRP-ribosome complex binds to SRP receptor
-complex comes into contact with protein translocator & SRP is released
-signal peptide triggers opening of protein translocator (translocon) and enters through open pore

Front 190

translocon

Back 190

-protein translocator (sec61 complex)
-includes several protein complexes that together form an aqueous pore in the membrane through which the newly synthesized polypeptide chain crosses the membrane lipid bilayer

Front 191

soluble, secreted proteins

Back 191

-usually have an N-terminal signal peptide which is cleaved by signal peptidase during translocation

Front 192

cotranslational translocation

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-these events produce a soluble protein that is moved (translocated) during synthesis from the cytosol to the ER lumen

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entry into the ER is the start of...

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-delivery to the exoplasmic face, eventually extracellular space

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The sugar groups on glycoproteins and glycolipids...

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-face the exterior & not the cytosol

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characteristic topologies of membrane proteins...

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-are established during biosynthesis

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synthesis of integral membrane proteins

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-N-terminal signal sequence specifies start transfer
-after translocation begins, a second hydrophobic sequence acts as a stop transfer signal
-the second sequence also eventually anchors the protein in the membrane after the N-terminal signal peptide has been released from the translocon and cleaved off

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multipass transmembrane proteins

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-span the bilayer several times
-have a series of start and stop transfer signals
-ex. Rhodopsin - a plasma membrane protein that functions to process light in the retina

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GPI anchors added to some proteins

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-short sequence of amino acids in the lumenal region is recognized by an endopeptidase that both cleaves the protein & transfers the remaining exoplasmic region to a preformed GPI anchor in the ER membrane
-when mature, a GPI-anchored protein will be facing the extracellar environment (inside of ER lumen corresponds topologically to the outside of the cell)

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asymmetry & orientation of membrane proteins

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-orientation established by cotranslation-translocation process that remains unchanged once it is established
-remains unchanged as membrane proteins are transported to their destinations in the cell

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modifications in ER lumen

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-cleavage of signal peptides
-cotranslational N-glycosylation
-trimming of N-linked sugars
-hydroxylation (Pro, Lys of collagens)
-disulfide bond formation
-protein folding
-assembly of multimeric proteins

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addition of N-linked oligosaccharides

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-a pre-assembled oligosaccharide (attached to a dolichol phosphate intermediate) is transferred to an Asn on the growing polypeptide chain as it enters the ER lumen
-utilizes an oligosaccharyl transferase to perform transfer

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protein folding & assembly of multimeric proteins

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-critical activities within the ER
-quality control maintained by chaperone proteins such as:
-protein disulfide isomerase (PDI)
-Hsc70 (aka BiP)
-Calnexin
-Calreticulin

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ER resident proteins

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-have a sequence that is recognized by KDEL receptors in the membranes of small transport proteins
-this is used to return the proteins to the ER if the escape into the cis Golgi

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Cystic Fibrosis

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-lethal autosomal recessive disease
-characterized by abnormal ion & water transport that results in accumulation of abnormally thick mucus in lungs
-disease caused by mutation in CFTR (usually a phenylalanine deletion)

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delta 508F mutation

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-mutation in cystic fibrosis
-interfers with proper folding of CFTR and causes it to be retained in the ER
-CFTR fails to reach the plasma membrane where it is needed to function as a regulated chloride channel

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cellular quality control

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-misfolded proteins are retrotranslocated to the cytosol & degraded there by proteasomes (ERAD)
-ER associated degradation

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if proteins are properly folded & oligomerized...

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-they can leave the ER and move onto the Golgi & through the secretory pathway