Cell And Molecular Biology

Front 1

Cell theory

Back 1

All living cells are formed by the division of existing cells. Living organisms do not arise spontaneously.

Front 2

Extracelluar matrix (ECM)

Back 2

A dense material often made of protein fibers embedded in a polysaccharides gel.Collagen is the major component.

Front 3

Cell characteristic of prokaryotes

Back 3

No nucleus, no membrane-bound organelles, and the DNA is circular.

Front 4

Cell characteristics of eukaryotes

Back 4

The DNA is linear. The cytoplasm fills the cell interior. The cell membrane encloses the cell.

Front 5

Describe the nucleus in Eukaryotic (3)

Back 5

-- Nucleus makes up 10% of cellular volume and contains DNA.
3 Parts
-- Nucleolus: rRNA synthesis, assembly of ribosomal subunit.
-- Heterochromatin: dark area of nucleus, non-conding DNA.
-- Nuclear envelope: it contains nuclear lamin, nuclear pore.

Front 6

What 3 proteins does nuclear pore have?

Back 6

It has Fiber, Basket, Ring protein.

Front 7

Describe the functions of Golgi Apparatus (3)

Back 7

It has a pancake structure near the nucleus
-- It does lipid synthesis
-- It does protein modification, packaging, sorting
-- Often receives and chemically modifies molecules made in ER -- directs to exterior of cell or various locations in cell.

Front 8

Describe order of Golgi

Back 8

cis Golgi -> medial Golgi -> trans Golgi -> cell membrane

Front 9

Describe the ER

Back 9

It is the Endoplasmic Reticulum. Irregular maze of interconnected spaces enclosed by a membrane.
-- It does protein and lipid synthesis.

There are three types
a) Rough ER
b) Smooth ER
c) Sarcoplasmic reticulum

Cell membrane components, and materials destined for export are made.

Front 10

Rough ER

Back 10

It is studded with ribosomes.
It is involved in protein translation, folding and transport of proteins.

Front 11

Smooth ER

Back 11

It synthesis lipids, steroids, and metabolizes carbohydrates.

Front 12

Sarcoplasmic Reticulum

Back 12

It is a special type of smooth ER found in smooth and strained msuscle.
-- Contains large stores of Ca+, which is released when muscle is stimulated.

Front 13

What are the 2 double membrane organelles

Back 13

Mitochondria and chloroplast.

They are both energy centers and they contain DNA

Front 14

What are the 2 organelles are enclosed in vessicles

Back 14

Lysosomes (degradation center of cell)

Peroxisome (detoxification centers of the cell)

Front 15

Mitochondria functions

Back 15

Mitochondria resembles bacteria, and is thought to have a symbiotic relationship. They produce ATP from oxidation of sugars.

Consumes oxygen and releases carbon dioxide(cellular respiration)

Front 16

Chloroplasts functions

Back 16

Only in plants and algae. They have internal green pigments called chlorophyll. They get energy from sunlight.

They carry on photosynthesis. Converts light energy to chemical energy via chloroplast releasing oxygen.

Then uses mitochondria to turn oxidize this energy for use,

Front 17

Function of Lysosomes

Back 17

They're small, irregularly shaped organelles. Digestion occurs, recycling and degradation of unwanted molecules.

Releases nutrients from food particles, and readies other molecules for excretion.

Front 18

Functions of Peroxisomes

Back 18

Small, membrane enclosed organelle. It breaks down potentially dangerous substances.

Front 19

Endocytosis

Back 19

Animal cells that can engulf very large particles, entire foreign cells.

Front 20

Exocytosis

Back 20

Vesicles from inside the cell fuse with plasma membrane and release contents into external medium. Ex. Hormones, neurotransmitters, and other signal molecules.

Front 21

Cytosol

Back 21

It is not partitioned off within intracellular membranes. Site for many chemical reaction.

Front 22

Antibody chains

Back 22

It has a a "Y" shape. It has heavy and light chains.

Light chain (variable domain)
Heavy chain (constant domain)

Variable domain binds antigen.

Front 23

Antibody characteristic

Back 23

Every antibody recognizes a specific antigen.

Front 24

Affinity Chromatography

Back 24

Method of separating biochemical mixtures, based on a highly specific biological interaction such as that between antigen and antibody,

Ability to collect pure antigen.

Front 25

Immuno-histochemistry

Back 25

Uses Primary and Secondary antibody.

Primary is generated in a host organism such as mouse.

Secondary is conjugated with fluorescence.

Front 26

What 3 elements are found in high concentrations outside the cell?

Back 26

Sodium, Calcium, Chlorine

Front 27

What 2 elements are found in high concentrations inside the cell?

Back 27

Potassium and Hydrogen

Front 28

2 properties determine diffusion rate of molecules

Back 28

Size and Solubility

Front 29

What kind of molecules are readily diffused

Back 29

-- small, hydrophobic
-- small, uncharged polar

Front 30

What kind of molecules are impermeable?

Back 30

-- large uncharged polar
-- ions

Front 31

What are the two major classes of membrane transport proteins?

Back 31

Carrier: with specific binding sites for ions and compounds. Specific ligand

Channel: Mainly for ions, by size and charge

Front 32

What are all the different kinds of membrane transport? (5)

Back 32

-- Carrier proteins
-- Channel Proteins
-- Passive transport
-- Electrochemical gradient
-- Active Transport

Front 33

What is passive transport?

Back 33

It includes all channel and carrier proteins. It is driven by concentration gradient.

Conformation changes of the carrier.

Front 34

Glucose carrier on liver cell

Back 34

It is a passive transport using a 12-transmembrane protein. Involves switch between 2 conformations.

Front 35

Electrochemical gradient

Back 35

It is part of passive transport.

It is for charged molecules.

Driven by concentration gradient + Membrane potential.

Membrane potential is the voltage difference across a membrane (-60mv inside)

Front 36

What is Active Transport.

Back 36

Active transport needs energy and can only be done by "special carrier proteins".

It moves solutes against electrochemical gradients.

Front 37

What are the 3 ways of active transport?

Back 37

1) Coupled transport: 1 molecule going uphill, the other down hill. [Symport and Antiport]

2)ATP-driven: ion pump. It is just one up hill using ATP. (Na+ pump)

3) Light-driven: mainly in bacteria.

Front 38

What is Na+--K+ pump?

Back 38

--It is a type of coupled transport.

--Uses ATP to pump Na+ out, and pump K+ in.

-- 30% of ATP is used by carrier proteins
-- there is zero driving force for K+ influx
--Cyclic action of the carrier proteins

Front 39

What is the cyclic action of carrier protein? (6 steps)

Back 39

1) Na+ binds to the carrier protein from inside the cell (cytosolic)

2)Then ATP is used to change conformation of carrier protein

3) Carrier protein then opens up to the outside of the cell and releases Na+

4) As the conformation of the protein is still facing the outside of cell, K+ binds to the carrier protein

5) The protein changes conformation again and open up on the inside of the cell (cytosolic)

6) This releases the K+

The K+ required no energy because it had 0 driving force.

Front 40

What are the 2 types of Coupled Transport?

Back 40

Coupled Transport is part of Active Transport which requires energy.

1) Symport: 2 molecules transported both in the same direction

3) Antiport: 2 molecules transported, but in different directions.

Front 41

What is Glucose-Na+ pump?

Back 41

It is a "symport protein", part of "coupled transport" which is a type of "active transport".

Steps
1) The protein is opened outside of cell, allows glucose and Na+ to bind.

2) Uses Na+ potential to facilitate change

3) The protein changes the conformation and releases glucose and Na+ inside the cell.

Front 42

What is the point of Glucose-Na+ pump?

Back 42

The pump helps move glucose from the intestinal lumen to the inside of the cell.

From there, glucose can passively transport into the extracellular fluid (blood)

Front 43

Glucose Carrier (Carrier Protein, Location, energy source, function).

Back 43

-- Located in plasma membrane.

-- No energy source needed

-- Passive import of glucose.

Front 44

Na+-driven glucose pump (Carrier Protein, Location, energy source, function)

Back 44

-- Located in apical plasma membrane of kidney/intestinal cells.

-- Na+ potential(gradient)

-- Active import of glucose

Front 45

Na+-H+ Exchanger

Back 45

-- In plasma membrane

-- Na+ gradient

-- Active export of H+ ions, regulates pH

Front 46

Na+-K+ pump (Carrier Protein, Location, energy source, function).

Back 46

-- Plasma membrane

-- ATP

-- Active export of Na+, and passive import of K+

Front 47

Ca+ pump(Carrier Protein, Location, energy source, function).

Back 47

-- Plasma membrane

-- ATP

-- active export of Ca2+

Front 48

H+ pump (Carrier Protein, Location, energy source, function).

Back 48

-- Located in membranes of lysosomes

-- ATP

-- active export of H+ from cytosol into vacuoles.

Front 49

What is Ion channel?

Back 49

It is an aqueous pore in a lipid membrane, walls of protein which selects which ion/molecules can pass.

Front 50

What does Ion Channel selectivity depend on?

Back 50

-- Depends on the diameter and shape of the Ion Channel, and its distribution of charged amino acids in the protein lining.

Front 51

What are 4 elements highly selective of ion channel?

Back 51

Na+, K+, Cl-, Ca+2

Front 52

What regulates Ion Channel?

Back 52

-- It is regulated by a signal, which "opens" or "closes" channel.

-- When open -- 1000x more ions flow in compared to carrier protein

-- It can change membrane potential.

-- When closed, none get in.

-- It can cause reactions in other ion channels forcing some to open/close

-- Generates electrical signal across membrane.

Front 53

Patch-Clamp recording

Back 53

It is a in-vitro tool to study ion channels.

-- Uses glass microelectrode
-- This attaches to cell membrane and detaches a patch containing ion channels.
-- Metal wires are then connected to glass mircoelectrode and voltage is applied.
-- The result is recorded in Oscilloscope.

Front 54

What are the 4 gating stimuli for Ion Channels?

Back 54

1) Voltage-gated: The channel protein reacts to changes in voltage (positive/negative)

2) Ligand-gated (extracellular): neurotransmitter-gated (Glutamate).

3) Ligand-gated (intracellular); chemical-gated.

4) Mechanically gated: such as ions channels on auditory hair cells, and in Venus Flytrap.

Front 55

What are the 3 characteristics of Neurons?

Back 55

1) cell body
2) Long axon which ends in branches of
3) Nerve terminals which conduct signals away from cell body to
4) Dendrites which are shorter, branching which receive signal.

Front 56

Action Potential

Back 56

-- This is used for quick, long-distance communication.

-- It is triggered by sudden, local depolarization of plasma membrane.

-- Dramatic change from threshold potential to peak of action, back to threshold potential.

Front 57

Threshold potential

Back 57

It is the voltage going from -60mv to +40mv. Result of sudden depolarization.

Front 58

Voltage gated Na+ channel

Back 58

This controls action potentials of neurons.

Front 59

3 conformations of Voltage-gated Na+ channel

Back 59

closed --> open --> inactivated

1) closed: to maintain membrane potential at -60mv
2) open: membrane depolarized -60mv to +40mv
3) inactivated: it restores membrane potential by using Na+-K+ pump. Stops indefinite depolarization.

Front 60

Propagation of action potentials

Back 60

An action potential travels away from site of depolarization.

Front 61

Resting State (Neuron)

Back 61

In "Pre-synaptic Nerve Terminal", there are "Synaptic vesicle" filled with "Neurotransmitter".

The Voltage-gated Ca+2 Channel located on the Pre-synaptic nerve terminal is closed.

Front 62

Electrical to Chemical Signal

Back 62

1) Activation occurs (Ca+2 voltage gated is opened).

2) Causes the "Synaptic Vessel" to release its "Neurotransmitters" into the Synapse.

3) These "Neurotransmitters" then bind to "Ligand-gated" receptor located on the post-synaptic cell.

Front 63

Chemical to Electrical

Back 63

1) Once "Neurotransmitters" bind to Ligand-gated receptor

2) A change in membrane potential occurs (electrical)

3) Action potential generated on target cell.

Front 64

What are the 2 types of Synapses?

Back 64

Excitatory and Inhibitory

Front 65

Exitatory Synapse

Back 65

-- Causes an influx of Na+ which depolarizes membrane. This increases the likelihood of firing of action potential.

-- Ex: Acetylcholine [Na+], glutamate [Ca+2]

Front 66

Inhibitory Synapse

Back 66

-- Causes an influx of Cl- and keeps membrane polarized. It decreases the likelihood of firing an action potential.

-- Ex. GABA [Cl-], glycine [Cl-]

Front 67

Psychoactive drugs

Back 67

It targets "Transmitter-gated" ion channel.

a) Barbiturates and Tranquilizers: They bind to GABA-gated Cl- channels making it more sensitive to GABA's inhibitory action.

b) Antidepressant Prozac: blocks reuptake of "serotonin", increases excitatory action.

Front 68

Where is protein synthesized (translation)?

Back 68

It beings on ribosomes in the cytosol.

Front 69

Fate of a protein

Back 69

The "Signal Sequence" within amino acid sequence directs protein to organelles.

Front 70

What are signal sequence?

Back 70

-- They are about 15-60 amino acids long

-- Directs protein to organelles

-- They are removed after transport

Front 71

What are the different locations protein can go to from ER? (4)

Back 71

-- Golgi
-- Endosomes
-- Lysosomes
-- Cell surface

Front 72

Signal Sequence needed to import into ER

Back 72

[Leu-Leu-Val-Gly-Lle-Leu-Phe-Trp-Ala]

Front 73

Signal Sequence needed to import into Nucleus

Back 73

[Lys-Lys-Lys-Arg]
positively charged

Front 74

Protein through Nucleus

Back 74

Nucleus pore allows small water soluble molecules freely.

To help protein/RNA pass..
1) A "Nuclear Localization Signal" attaches to Protein

2) A "Nuclear Transport Receptor" attaches to "Nuclear Localization Signal" and helps it go through the nuclear pore

3) "Nuclear Transport Receptor" drops off the protein with "Nuclear localization signal" and returns back on surface.

Front 75

What is Nuclear Localization Signal

Back 75

-- This attaches to a protein, in turn attaches to "Nuclear Transport Receptor". To aid protein transport through nucleus.

-- It has 2 short sequences of positively charged amino acids (lysines or arginines).

Front 76

Ribosomes

Back 76

-- It contains 2 parts and mRNA is in between the parts.

-- As mRNA slides through the middle 3' to 5', a protein is made according to mRNA's instructions by the Ribosomes.

Front 77

Transport into ER (Soluble Protein) 6 steps

Back 77

1) As the protein is being made and pushed out of the Ribosomes, "Signal Recognition Particle" in cytosol binds to the protein.

2) The "Signal Recognition Particle" moves the entire ribosome with mRNA synthesizing protein to a location

3) This location is " Signal Recognition Particle Receptor" which is embedded in ER membrane.

4) The >8 hydrophobic amino acids "Signal Sequence" is used to open the translocation channel.

5) The protein is then translocated into the ER lumen.

6) The "Signal Peptidase" cuts off the protein and the whole protein is inside ER lumen

Front 78

Transport into ER (Single Transmemebrane protein)

Back 78

1) As the protein is being made and pushed out of the Ribosomes, "Signal Recognition Particle" in cytosol binds to the protein.

2) The "Signal Recognition Particle" moves the entire ribosome with mRNA synthesizing protein to a location

3) This location is " Signal Recognition Particle Receptor" which is embedded in ER membrane.

4) There are "Hydrophobic Start-transfer Sequence" and "Hydrophobic Stop-transfer Sequence".

5) The "Start-transfer" initiates the sequence and brings the protein into ER lumen

6) But when "Stop-transfer" sequence is hit, the protein halts its move into the ER lumen

7) As a result, the protein is half in, half out (transmembrane)

Front 79

Protein modification in ER

Back 79

-- Primary glycosylation: adding 14-sugar oligosaccharides on a amino side chain of "Asparagine"

-- This is called "N-linked" glycosylation.

(Protein is also further modified in Golgi)

Front 80

Order of protein Transport

Back 80

ER --> cis Golgi --> medial Golgi --> trans Golgi --> Plasma Membrane/Endosomes

Front 81

Where does vessicle tranport used?

Back 81

From ER to
Golgi
Endosomes
Lysome
Cell Surface

Front 82

Vesicle coat

Back 82

Shapes membrane into a bud and helps capture molecules for onward transport

Front 83

What are 2 types of Vesicle Coat?

Back 83

1) Clathrin coated

2) COP coated

Front 84

How does Clathrin Coated Vesicles form? (5)

Back 84

1) Cargo molecules inside the organelle bind to "Cargo Receptor" at transport signals

2) "Adaptins" bind to "Cargo Receptors" and form a trap

3) "Clathrin Coat" binds to "Adaptins" and form a circle enclosing the "Cargo Molecules"

4) Dynamin makes a ring around the "Coated Pit" and pinches off the vesicle.

5) Once a vesicle, the "Clathrin Coat" is shed

Front 85

Clathrin coated vesicle functions

Back 85

Only originate from "Golgi appratus", " Plasma Membrane"

Only destination "Lysosome", "Endosome"

Front 86

COP coated Vesicles

Back 86

Only originate from "ER", "Golgi cis", "Gogli apparatus"

Only destination "Golgi apparatus", "Golgi cis", "ER"

Basically ER to Golgi, and Golgi compartments

Front 87

Vesicle docking

Back 87

-- The 2 different SNARE must match up correctly -- (vSNARE to tSNARE) and vice versa.

-- When they match up correctly, the protein is transported into the necessary destination

Front 88

LDL Receptor

Back 88

This is part of "Receptor Mediated Endocytosis".

a) When cholesterol is injected, a Clathrin-coated vesicle packs around them.

b) The vessicle pinches off and fuses with "Endosome"

c) "Endosome" then pinches off another vesicle with the LDL and fuses with Lysosome

d) Result is free cholesterol that is often in blood stream

Front 89

Pinocytosis (Endocytic Pathway)

Back 89

Cellular drinking, fluid and macromolecules degradation.

Front 90

Phaocytosis (Endocytic Pathway)

Back 90

Cellular eating. Like when a bacterium enters a cell. It is degraded quickly. A "Phagosome" forms around it and taken to lysosome.

Front 91

Transcytosis

Back 91

Transport from one EC space to another EC

Front 92

Endosome

Back 92

Main sorting station in the inward endocytic pathway.

It can:
a) Recycle: send it to plasma membrane

b)degradation: send it to lysosome.

c) transcytosis: send it to another EC

Front 93

Lysosome

Back 93

Degradation center, has acid Hydrolases with a pH 5

Front 94

Autophagy

Back 94

Old organelles have "Autophagosome" form around them and taken to lysosomes.

Front 95

Yeast Cell Life

Back 95

-- Haploid or Diploid

-- Mating: alpha and beta can mate

-- Adenine Pathway contains 12 enzymes

-- Adenine mutation in enzyme "AIR" turns it red

Front 96

What are 4 ways of cell communication?

Back 96

1) Endocrine: Long distance

2) Paracrine: Short distance

3) Neuronal: Nervous system

4) Contact dependent

Front 97

Endocrine

Back 97

-- The single molecule is "Hormones". Affects cells very distant from releasing cell.

-- Produced through circulatory system, signal travels via blood stream.

Front 98

Paracrine

Back 98

-- The signal molecules are short lived and have local effects.

-- Target cells are located locally.

-- Can coordinate activity of neighbor cells

-- Secreting cell might start a process "Autocrine"

Front 99

Neuronal

Back 99

-- The signal molecules are neurotransmitters and are located in nervous system.

-- Short lived, happens at synapse

Front 100

Contact dependant

Back 100

Signaling protein and target protein are touching.

Front 101

What are the 2 types of receptors?

Back 101

1) Cell surface receptor: Hydrophillic signal molecules

2) Intracellular receptors:small, hydrophobic signal molecules.

Front 102

What are the 2 types of "Cell Surface" receptor?

Back 102

1) Ion channel

2) G-protein: has 7 transmembrane proteins, and is common in "vision", "smell", "taste", "chemoreception".

Front 103

Explain activation of G-protein

Back 103

G- protein consists of 3 subunits (Alpha, Beta, y)

1) When inactive, G-protein and receptor protein are not touching.

2) When a "Signal Molecule" binds to "Receptor Protein", the G-protein makes contact with the receptor protein (7transmembrane)

3) G-protein and Receptor Protein contact activiates GTP

4) Activation of GTP further breaks up G-Protein into "Alpha" and "Betha-y" signaling units

Front 104

Three things that can happen with an activated G-protein

Back 104

1) The activated B-y complex can open an Ion Channel (contributing to vision, smell, taste, chemoreception).

2) The contact of activated Alpha with an enzyme can cause small messenger molecules to diffuse and act on intracellular signaling proteins.

3) Adenylyl Cyclase / Phospholipase C

Front 105

Adenylyl Cyclase

Back 105

1) The G-protein has been activated via GTP and "Aplha" and "Beta-y" has separated

2) The activated Alpha subunit makes contact and activates "Adenylyl Cyclase" membrane-bound enzyme

3) The "Adenylyl Cyclase" enzyme in turn activates "Cyclic AMP" (2nd messenger)

4) "Cyclic AMP" in turn activates "PKA" (protein kinase A) (Intermediary protein)

5) This activated PKA goes through the nuclear pore and binds to the DNA and turns gene ON.

6) This results in "Transcription"

Front 106

Two most widely used 2nd messengers

Back 106

Adenylyl Cyclase uses ATP to make "Cyclic AMP" (2nd messenger)

IP3 signals ER to release Ca+2 (2nd messenger)

Front 107

Phospholipase C

Back 107

1) The G-protein has been activated via GTP and "Aplha" and "Beta-y" has separated

2) The activated Alpha subunit makes contact and activates "Phospholipase C" enzyme.

3) The activated "Phospholipase C" enzyme in turn activates "Inositol Phospholipid"

4) The "IP3" part of the "Inositol Phospholipid" detaches from itself.

5) The "IP3" binds to the ER's Ca+2 Ion Channel, realeasing a lot of Ca+2 ions

6) Ca+2 ions (2nd messengers) activate PKC (Intermediary protein)

Front 108

Enzyme-linked Receptor

Back 108

1) An inactive "Tyrosine Kinase" (usually contains kinase enzyme activity) is chilling.

2) A signal protein in form of a dimer binds to the "Receptor Tyrosine Kinease" causing it to experience "Dimerization"

3) This "Dimerization" activates the "Tyrosine Kinase" and causes it to experience "Autophosphorylation" of receptors

4) The "Phosphorylated Tyrosines" serves as a binding site for "Adaptors" (intracellular signaling proteins) protein.

5) The result can be cell proliferation, differentiation, or death.

Front 109

Adaptor and Ras Signaling

Back 109

1) After the "Adaptors" (intracellular signaling proteins) protein have bound to the "Phosphorylated Tyrosines".

2) The "Adaptor" protein binds to "Ras-activating" protein.

3) "Ras-activating" protein signals "Ras" protein to go from inactive (GDP) to active (GTP), as "Ras" protein is a GTp binding protein

4) Activated "Ras" protein relays signal through series of "MAP"(Mitogen-Activated Protein_

Front 110

What is a dimer?

Back 110

It is a chemical or biological entity consisting of two structurally similar subunits called monomers, which are joined by bonds, which can be strong or weak.

Front 111

What are the five purposes of Signal Transduction?

Back 111

1) To transform signal into molecular form

2) Spread the signal through all space

3) Amplify the signal

4) Distribute or diverge the signal

5) Modulate and cross interact.

Front 112

Explain the order of "Signal Transduction"

Back 112

Extracellular Signal Molecule --> Receptor Protein --> Intracellular Signaling Proteins --> Target Proteins --> (Altered metabolism/altered gene expression/altered cell shape/movement)

Front 113

Describe the MAP/Ras Signaling Pathwaysy

Back 113

1) Active "Ras" protein activates "MAP-kinease-kinease-kinease"

2) Using ATP synthesis, "MAP-kinease-kinease-kinease" activates "MAP-kinease-kinease"

3) Using ATP synthesis, "MAP kinease-kinease" activates "MAP-kinease".

4) Using ATP synthesis, "MAP-kinease" activates "Target Proteins"

5) These target proteins in turn can affect Changes in protein activity, and Changes in gene expression

3)

Front 114

Side Notes about MAP

Back 114

-- Mitogen induces cell proliferation, and if left uncontrolled can lead to cancer.

-- Phosphorylation occurs at serine/theronine. (Addition of phosphate group).

-- MAPKKK pathways, all of them were "Serine/Threnine" pathways

Front 115

Mutation studies

Back 115

Are done to study protein functions. By altering and changing one thing, one can observe the results and learn.

Front 116

Constitutively Active Ras

Back 116

"ON all the time".

-- A mutation causes an always active Ras, can't stop GTP.

-- The mutant thus continuously sends signals, even when there is no signal molecule.

Front 117

Loss of function

Back 117

-- Ras requires Protein X and Y

Signal --> Protein X(mutated-inactive) -->Ras (inactive) --> Protein Y (inactive)

Because Protein X is mutated, there is a "Loss of Function" and the upstream of signal halts.

Front 118

Gain of function

Back 118

No Signal --> Protein X(mutated-inactive) -->Ras (mutated active) --> Protein Y (active)

This results in a "Gain of Function" as even when there is no signal, Ras has started signaling upstream.