Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

MCB Block 3 > Organelles > Flashcards

Organelles Flashcards

1
Q

What are cell membranes primarily composed of? How is it arranged?

A

(Only lipid components are listed)
Phospholipids (most abundant)
Glycolipids (only on outside)
Cholesterol

The phospholipids are arranged so the extracellular and intracellular leaflets are hydrophilic, and the space in between the leaflets is hydrophobic.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

What is a glycolipid? Does it have a specific orientation?

A

A glycolipid is a protein with a carbohydrate chain located ONLY on the extracellular leaflet.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

What is special about glycolipids?

A

The carbohydrate chains coming off the glycolipid determine what the cell is able to interact with.

The carbohydrate chains are collectively called the glycocalyx.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

What is the difference between an integral protein and a peripheral protein?

A

Integral: transmembrane protein (it spans the entire membrane)

Peripheral: interacts/involved with membrane but doesn’t really enter/cross it. (?typically associated with integral proteins?)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What purpose does cholesterol serve in the membrane?

A

It increases rigidity of the membrane, preventing components from moving around (especially in membranes with high unsaturations or in high heat conditions)

(For block 3, cholesterol does not affect fluidity. For everything else, it does.)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

How would you sum up the differences between prokaryotic cells and eukaryotic cells?

A

Prokaryotic cells are much smaller than eukaryotic cells, and carry no organelles/cytoskeleton.

Prokaryotic DNA is circular and singular, as opposed to the multiple linear DNA molecules of eukaryotes.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Differentiate between gram negative and gram positive cells.

A

Gram negative: stain pink, contains TWO membranes and a THIN cellular wall in between them

Gram positive: stain purple, contains ONE membrane and a THICK cellular wall on top of it.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

What are the functions of the membrane?

A
  • Transporter proteins regulate movement of molecules across membrane
  • Protect cell and provide structure
  • compartmentalize biological activity
  • contribute to cellular signalling (via membrane proteins)
  • provide structure for biochemical activity (like ATP production)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

What are the protein components of the cell membrane?

A
  • Channel/Pump proteins
  • Transporters
  • Receptors
  • Adhesion molecules
  • Gap junctions

(try and understand what each does)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

What special quality do membrane lipids have that contribute to how they comprise the membrane?

A

They’re amphipathic, meaning they have hydrophobic and -philic components.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Describe the general structure of a phospholipid.

A

One hydrophilic (polar) head

Two hydrophobic (nonpolar) hydrocarbon, fatty acyl tails

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

What determines membrane properties and how?

A

Phospholipid tail length and degree of saturation.

An unsaturated tail will form a ‘kink’ due to cis-double bonding. More kinks = more fluid membrane.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

What happens to the membrane during apoptosis? What facilitates this?

A

Phosphatidylserine will ‘flip,’ inducing phagocytosis by macrophages.

Facilitated by ‘flippase’ enzymes.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

What determines how lipids will assemble into aggregates?

A

Their hydrophobic interactions with water.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

What lipid types become what aggregates?

A

Fatty acids - Micelles

Phospholipids - Bilayer, Liposomes

Note: shape of individual lipids determines what aggregates they will form.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

What holds the membrane leaflets (extra- and intracellular) together? What property do membranes have because of this?

A

Van der Waals interactions = weak bonds between hydrophobic tails.

This means that membranes are fluid and self-healing!

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

Why is membrane fluidity important?

A

It is essential for exocytosis, endocytosis, and membrane trafficking/biogenesis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

How can the function of membrane lipids/proteins be disrupted?

A

Interference with anchoring(?)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

What can increase the fluidity of a membrane?

A
  • unsaturated fatty acid tail (cis-double bond kinks)
  • short chain
  • increase in temperature
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

What is an acanthocyte? What is another name for it?

A

A red blood cell with too much cholesterol, which causes its shape to deform. It will have 5-10 irregular, blunt, finger-like projections, and is less susceptible for deformation.

aka spur cell

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

What is dangerous for a patient with a high reticulocyte count? What has caused their condition?

(See slide 28 for details)

A

If the patient eats anything sharp, they’re in danger. Clotting time has been increased (PT) and distorted cholesterol balance in plasma and RBC membrane will cause the bleeding to clot very slowly.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

What conditions are acanthoctyes associated with?

A

Spur cell anemia, chronic liver disease

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

What are lipid rafts?

A

islands of cholesterol and glycosphingolipids (long saturated tails) that are less fluid and more thick than the surrounding leaflet. They stick out a little due to the longer tails of the glycosphingolipids

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

What are contained by lipid rafts?

A

integral and peripheral membrane proteins: clustering allows them to function together

GPI anchors: glycolipid that anchors the proteins to the plasma membrane

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

Name the enzymes responsible for lipid movement within the bilayer (flip-flop) and their functions.

A

Flippases - phospholipid specific

Scrambalases - non-specific scrambling: mix up newly-synthesized PLs. Activate during apoptosis.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

What is the typical ratio of lipids to proteins in PMs?

A

1:1
Note: Proteins are larger and heavier than lipids, so this ratio still means that there are about 50 phospholipids per protein.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

What are the functions of membrane proteins?

A
  • Transport
  • Anchor membrane to macromolecules on either side
  • Signal Transduction (receptors)
  • Enzymatic activity
  • Cell Identity markers
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

List the 3 classes of membrane proteins. What do they do?

A

Integral
- signalling and adhesion, channels, transporters/pumps

Peripheral
- part of cytoskeleton, cytochrome C

Lipid-anchored (peripheral)
- signalling and adhesion

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q

What are the lipid anchors, and where do they operate?

A

GPI anchors
- link proteins to outer leaflet

Fatty acylation or Prenylation
- link proteins to inner leaflet.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
30
Q

In RBCs, what are the four membrane proteins plus one cellular component that gives the RBC its deformable structure?

A

Transmembrane Proteins:

  • Band 3
  • Glycophorin

Peripheral:

  • Ankyrin
  • Protein 4.1?

Spectrin network is the meshwork that reinforces the bilayer.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
31
Q

Describe how the RBC membrane proteins interact with each other and the spectrin network to allow for a deformable structure.

A

Band 3 is interspersed throughout membrane. Ankyrin binds to Band 3 proteins and Glycophorins, attaching the spectrin cytoskeleton to the membrane. Ankyrin also is then linked to Protein 4.1, which is bound to Actin filaments.

(See slide 40 for a picture OR DRAW ONE YOURSELF YOU LAZY TWIT)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
32
Q

What causes Hereditary Spherocytosis and what can result from it?

A

A defect in RBC spectrin, ankyrin, or protein 4.1. A defect with spectrin may involve spectrin deficiency.

This condition may cause hemolytic anemia, due to the RBCs becoming spherocytes.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
33
Q

What are spherocytes? How do you distinguish these from normal RBCs?

A

They are RBCs that have all but lost deformability, and have taken a smaller, spherical shape that is vulnerable to splenic sequestration and destruction.

Spherocytes appear the same as normal RBCs, but noticeably lack the area of central pallor (where the indentation of a normal RBC would be).

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
34
Q

How do the locations of membrane proteins in relation to the ACTUAL CELL affect their function?

A

Apical: regulation of secretion/intake

Lateral: cell-to-cell communication/attachment

Basal: anchoring/adhesion of cell

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
35
Q

What are tight junctions, and where are they located?

A

The interaction of a transmembrane protein with another transmembrane protein of another cell. This interaction is impassable by other proteins, and is always located at the apicolateral border of cells.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
36
Q

What functions does the glycocalyx serve?

A
  • Protection (from acid and enzymes)
  • Recognition and Cell adhesion
  • Repulsion (negative charge of sialic acid sugars)
  • Embryonic Development (guide embryonic cells to destination)
  • Different in cancer cells, which allows for immune recognition/anti-cancer therapy
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
37
Q

The primary markers for cell recognition are:

A

carbohydrates

  • attachment for bacteria, viruses, toxins, other cells
  • WBCs attach to selectins expressed by activated endothelial cells.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
38
Q

Why does the nucleus require compartmentalization?

A
  • protect DNA from harsh cytosolic environment

- separate ribosomes from pre-mRNA to prevent translation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
39
Q

Describe the nuclear envelope and its characteristics/components.

A

It has a double lipid bilayer with a perinuclear space (intramembraneous)

  • Outer membrane and perinuclear space continuous with rER membrane and lumen
  • Inner membrane supported by nuclear lamina
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
40
Q

What is the Nuclear Pore Complex (NPC)? What is composed of?

A

Protein complex that allows transport of cargo in and out of nucleus.

Composed of Nucleoporins (glycoproteins)

  • Cytoplasmic ring = 8 subunits
  • Luminal ring = 8 subunits
  • Nuclear ring = 8 subunits
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
41
Q

How selective is the NPC? What are examples of cargo it would transport?

A

Small molecules (~9 nanometers) are passively diffused

Macromolecules are selectively, actively transported.

  • import: proteins, snRNPs, snoRNPs
  • export: mRNA, tRNA, ribosomes
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
42
Q

How does the NPC import/export cargo?

A

Cargo Proteins have either a Nuclear Localisation Signal (NLS) or Nuclear Export Signal (NES).

Appropriate protein binds the NLS/NES and nucleoporins, importing/exporting the cargo proteins
- Importin and Exportin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
43
Q

The NPC requires energy. How does it acquire it?

A

RAN GTPase (G-protein) will switch on or off depending on location, facilitating transport. They bind to GDP or GTP.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
44
Q

What do GEFs and GAPs do? Where are they located?

A 
GAPs hydrolyze (attack) GTPs
GEFs exchange GDPs for GTP

GAPs are always in the CYTOPLASM, GEFs are always in the NUCLEUS.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
45
Q

Describe the mechanism of importing/exporting a cargo protein.

A

Import:

  • Importin will bind cargo and import it.
  • RAN GEF will bind a GTP and bind to importin, causing it to release cargo in nucleus.
  • RAN-GTP bound Importin will travel to cytoplasm
  • RAN GAP will break GTP into GDP, and break RAN GDP off Importin,

Export:

  • RAN GEF makes RAN-GTP complex, which binds to exportin, causing it to pick up cargo and export it.
  • RAN GAP will break RAN-GTP to RAN-GDP and remove it, causing exportin to drop cargo in cytoplasm.
  • Exportin will return to nucleus to repeat cycle.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
46
Q

What mRNA is allowed through the NPC?

A

RNA-protein complexes. Export proteins will only allow mature mRNA through (5’ cap, poly A tail, spliced).

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
47
Q

What is the Nuclear Lamina and what is its function?

A

Network of proteins including Lamins (intermediate filaments) A, B, and C, which are high-tensile proteins.

It lines the inner surface of nuclear envelope to maintain structure and protect the membranes. It also provides an anchoring site for chromosomes and a method of regulation for transcriptioni factors.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
48
Q

Where do chromatin fibers bind to the nuclear lamina (and inner membrane)?

A

On their telomeres and centromeres. Each chromosome will only occupy its defined territory, and will not overlap with another.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
49
Q

What happens to the nuclear lamina and envelope during mitosis? How?

A

It disintegrates.

Cdk1 will phorphorylate the lamins of lamina, prepping for lamina disassembly.

Inactivation of Cdk1 will dephosphorylate the lamins, marking reassembly of the envelope and lamina.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
50
Q

What are laminopathies? What are examples?

A

They are (rare) conditions in which the components of the nuclear lamina/envelope have defects, typically regarding lamin assembly and attachment to the nuclear envelope.

Examples:

  • Skeletal/Cardiac Muscular Dystrophy
  • Lipodystrophy
  • Progeria
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
51
Q

When do the symptoms of laminopathies typically present?

A

During childhood.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
52
Q

What are general results of having defects with lamin assembly/attachment to the nuclear envelope?

A

Fragile nuclear envelope (can affect physically stressed tissues like muscle, bone, skin, etc.)

Disrupts nuclear function: aberrant distribution of chromosomes or interaction with specific TFs is altered.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
53
Q

What are examples of Skeletal and Cardiac Myopathies?

A

Emery-Dreifuss Muscular Dystrophy

Dilated Cardiomyopathy

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
54
Q

What is the pathology of Emery-Dreifuss Muscular Dystrophy?

A

Defect: Mutation in Emerin or Lamin A/C

Symptoms: Muscle weakness and atrophy. Sudden heart failure is common due to conduction defects and heart failure.

Cytology: Nuclear envelope is disrupted; chromatin extruded into the plasma.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
55
Q

What is the pathology of Dilated Cardiomyopathy?

A

Defect: Lamin A/C (rare cause)

Symptom: Nuclear lamina is very fragile; results in cell death due to nuclear structures/contents being damaged. Leads to congestive heart failure.

Note: on an X-ray the heart will appear to be much larger than normal.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
56
Q

What is the pathology of Lipodystrophy?

A

Defect: Lamin A/C
- preLamin A interacts with adipocyte TF, which impairs differentiation.

Symptoms: Accumulation of adipose tissue in face and neck, but significant peripheral lipoatrophy with muscle prominence.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
57
Q

What is the pathology of Hutchinson-Gilford Progeria Syndrome?

A

Colloquially known as ‘premature aging’

Defect: Altered Lamin A
- Unstable nuclear envelope. Bleb (herniation) formation and NPC clustering interference with importin/exportin function. Results in progressive nuclear damage and premature cell death, especially in cells that undergo more mechanical stress than other cells.

Symptoms: prominent eyes, alopecia, loss of subcutaneous fat, aged-looking skin, joint stiffness.

Note: Autosomal Dominant, but can USUALLY ONLY result from germ-line mutation due to condition preventing viable reproduction.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
58
Q

What the hell does Lamin A do that makes it so important to all the laminopathies??

A

It binds to:

  • Architectural partners
  • Chromatin partners
  • Gene-regulation partners
  • Signalling partners
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
59
Q

What are the prominent subnuclear structures? Which ones have membranes?

A

Nucleoli
Speckles
Cajal Bodies (CB)/Gems

NONE OF THEM HAVE MEMBRANES.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
60
Q

Briefly describe the function of each of the subnuclear structures.

A

Nucleoli: rRNA transcription and modification using snoRNPs.
“ribosome factories”
- PARTIAL assembly of ribosomes

Speckles: involved in mRNA modification using snRNPs

CBs/Gems: produce and modify snoRNA and snRNA before sending out into the cytoplasm. Usually paired. Gems also contain SMN (Survival of Motor neurons Protein)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
61
Q

What are the RNA molecules involved in subnuclear function? What is their pathway of maturation and end destination?

A

snRNA/snoRNA
snRNP/snoRNP

sn = small nuclear
sno = small nucleolar
  • CBs/Gems produce and modify snRNA and snoRNA.
  • snRNA/snoRNA is sent out into the cytoplasm, where they complex with proteins.
  • Complexes are now called snRNP/snoRNP
  • snRNP will head toward the Speckles for mRNA modification/splicing, snoRNP will head toward the Nucleolus(or multiple) for rRNA modification.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
62
Q

What is the pathology of Spinal Muscular Atrophy?

A

Defect: SMN Mutation - leads to defective snRNP assembly -> defective pre-mRNA splicing -> loss of motor neurons in spinal cord and brainstem.

Symptoms: Sudden onset/rapid progression of:

  • muscle weakness/atrophy
  • hypotonia
  • Dysphagia and feeding difficulties.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
63
Q

What does the number of nucleoli in a nucleus and their sizes say about a cell?

A

Larger nucleoli/multiple nucleoli indicate ribosomal activity (aka protein production) of the cell.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
64
Q

What produces snRNA and snoRNA?

A

RNA pol II

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
65
Q

What will snoRNP do specifically that contributes to ribosome assembly?

A

snoRNA region of RNP will have short sequences that are complementary to the rRNA. Base-pairing will catalyze base-modification of pre-rRNA (methylation).

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
66
Q

What happens to the nucleolus during and after mitosis?

A

It will disassemble during mitosis, and then reassemble around NORs following termination of mitosis.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
67
Q

What are NORs?

A

Nucleolar Organization Regions. they contain rRNA and serve as a hub for nucleolus to reform around once cell has bypassed mitosis and resumed rRNA synthesis.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
68
Q

What are the substructures of the Nucleolus? What are some major structures/identifiers of these substructures?

A

Fibrillar Centers: NORs (pre-rRNA genes located here) and TX inactive DNA

Pars Fibrosa (dense fibrillar components): rRNA undergoing TX and cleavage/modification by snoRNPs

Pars Granulosa (granular component): diffuse grey area of nucleolus. This is where initial assembly of ribosome proteins from rRNA begins.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
69
Q

What kind of cells need prominent/multiple nucleoli? List some examples.

A

Cells that replicate many times. These cells require many proteins. Examples are:

  • pancreatic cells
  • plasma cells
  • stem cells (developing hematopoietic precursors)
  • cancer cells
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
70
Q

Describe the relationships of the nuclear membrane, rER, and sER.

A

The outer leaflet of the nuclear membrane is continuous with the rER, and the rER is continuous with the sER.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
71
Q

What is the function of the rER?

A

The rER is responsible for protein production and modification (temporarily studded with ribosomes).

The ER is responsible for targeting and sending vesicles with its protein/lipid products.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
72
Q

What is the function of the Golgi Apparatus?

A

Postage center! Packages and transports molecules from the ER out of the cell (or to other organelles?).

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
73
Q

Where do the protein products of the rER go?

A
  • ER
  • Golgi Apparatus
  • Endosomes
  • Lysosomes
  • the Plasma Membrane
  • Secretion (out of the cell)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
74
Q

Describe the pathway through which a transmembrane (TM) protein would reach the plasma membrane.

A
  • TM proteins ‘threaded’ into rER membrane
  • membrane will pinch off to form a vesicle.
  • Vesicle moves to and becomes a part of the Golgi Apparatus
  • the Golgi Apparatus will pinch off the membrane containing the TM protein again and send it to the Plasma Membrane.

NOTE: notice how the TM protein never actually moves, the membrane that carries it is the component that does the actual moving.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
75
Q

How do lysosomal enzymes become a part of lysosomes?

A

Same way as TM proteins to PM, except vesicle budding off of rER is a lysosome instead.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
76
Q

What is the function of the sER? How does its function differ across cells?

A

General function:
- Membrane lipid synthesis/modification

In Hepatocytes:

  • Detoxification
  • Lipoprotein production

In skeletal muscle cells:

  • Store/release calcium for muscle contraction.
  • forms a network called the Sarcoplasmic Reticulum
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
77
Q

In what cells is the sER most prominent? What happens when it is stimulated?

A

Cells that synthesize steroids, triglycerides, and cholesterol.

Increases in size to secrete steroids/detoxify drugs.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
78
Q

What proteins are captured by the ER?

A
  • TM proteins

- Soluble Proteins (enter ER lumen for secretion/delivery to organelle)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
79
Q

What types of translocation are proteins involved in?

A

Cotranslational

Post-translational

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
80
Q

What kinds of proteins undergo Cotranslational translocation?

A

Same proteins that are captured by the ER.

TM proteins, Soluble Proteins

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
81
Q

What kinds of proteins undergo Post-translational translocation?

A

Pretty much every other protein. These are discharged in the cytosol.

(Ex. proteins targeted to nucleus, mitochondria, peroxisomes)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
82
Q

Describe the mechanism of Cotranslational Translocation.

A
  • Protein has an ER Signal Sequence (usually at N Terminus)
  • Signal Recognition Particle (SRP) binds to ER signal sequence
  • SRP binds to SRP receptor in ER membrane
  • SRP complex brings ribosome to a Translocon and transfers the ribosome to a translocation channel
  • SRP complex displaces; Ribosome transfers growing polypeptide chain through lumen of translocon.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
83
Q

Where does the ER signal sequence go during translocation? Why?

A

It remains in the lumen of the membrane (in the translocon) because it is hydrophobic.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
84
Q

What is BiP and why i s it important?

A

BiP (Binding Protein) is a lumenal ER chaperon, and it helps fold proteins properly as it is translated. It will bind the peptide that is in the lumen and pull it further into the ER.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
85
Q

What happens to an improperly folded protein?

A

It will never get further than the lumen of the translocon.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
86
Q

What is the fate of the ER signal sequence? What enzyme performs this function?

A

It is cleaved as the protein enters the ER lumen.

Signal peptidase

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
87
Q

What happens to a protein chain that has an additional hydrophobic region?

A

It becomes a Single-Pass TM Protein. The additional hydrophobic region will remain in the lumen of the translocon as the protein is synthesized. When synthesis is completed, the ER signal sequence is cleaved, and the finished protein is left embedded in the membrane as an integral protein..

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
88
Q

What is the additional hydrophobic region of a Single-Pass TM protein called?

A

Stop-transfer signal.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
89
Q

What is the internal signal sequence (start-transfer signal)?

A

Signal sequence that initiates translocation WITHIN the protein chain (not the same as a Signal Sequence). End of this sequence is inserted into the ER first.

THIS IS NOT THE STOP-TRANSFER SIGNAL, BUT IT IS WHERE THE PROTEIN WILL BE EMBEDDED IN THE MEMBRANE.

90
Q

What is a Multipass TM protein?

A

It is a protein with more than one of both start-transfer and stop-transfer sequences.

91
Q

Describe the mechanism of a Multipass TM protein being incorporated into the ER membrane.

A
  • Undergoes normal Single Pass TM protein translocation until second start-transfer signal is recognized.
  • Process is repeated multiple times in a ‘sewing’ motion. Protein will be threaded into the ER membrane.
92
Q

How are Single Pass TM Proteins translocated? Is there an exception?

A

Co-translationally.

The only exception is when the Carboxy terminus of the protein is located in the ER lumen; the protein will need to be fully synthesized in order for this to occur.

93
Q

Do the Single Pass and Multipass TM Proteins remain in the ER membrane?

A

No, they are sent to the Plasma Membrane.

94
Q

What happens to proteins as they’re transported to the PM?

A

Their orientation if ‘flipped.’ (Think about how the vesicles must approach the PM and where the protein ends were when they were being synthesized)

95
Q

What are rER resident proteins? What are the proteins we talked about in class called?

A

They are proteins that normally operate within the lumen of the ER. We discussed Chaperone proteins.

96
Q

What is the function of Chaperone proteins? List the three examples we learned.

A

Chaperone proteins bind to exposed protein domains that should not be exposed, folding the entire protein correctly so that those domains are no longer out in the open.

Ex. BiP, Calnexin, Calreticulin.

97
Q

What are the ‘faces’ of the Golgi Apparatus? What are their functions?

A

Cis-Golgi: receive from ER

Trans-Golgi: sort/package proteins and send to target

98
Q

What are some of the polypeptide processing steps in the rER? (5)

A
  • Formation of Disulfide bonds
  • Proper Folding
  • Addition/processing of carbohydrates
  • Specific proteolytic cleavage
  • Oligomerisation
99
Q

What happens to a polypeptide that remains misfolded after everything has been tried (like chaperone proteins)?

A

It is ejected into the cytoplasm, where it is de-glycosylated and poly-ubiquitinated for degradation by a proteosome.

100
Q

In N-linked Glycoslyation, where is the premade oligosaccharide chain assembled, and where does it go upon completion?

A

It is assembled on the Dolichol lipid

Once fully assembled, it is transferred to the Asparagine residue (on the NH2 group, hence N-linked).

101
Q

How is the oligosaccharide from N-linked Glycosylation further processed?

A

4 sugars are removed while it is still in the ER. This prepares it for transport to the Golgi, where it will continue to be trimmed/added to according to its purpose.

102
Q

Where does O-linked glycosylation occur, and on what residues?

A

In the Golgi Apparatus

Sugars are attached to the OH of selected Serine or Threonine residues.

103
Q

What is the general purpose of Glycosylation (N and O)

A

They are important for proper folding, transport, and function.

104
Q

Where are GPI-linked proteins assembled?

A

In the lumen of the ER.

105
Q

Walk through the process of Oligosaccharide Processing in glycolipid synthesis.

A
  • Protein synthesis eventually extrudes protein into ER lumen
  • (Branched) Oligosaccharide assembled on Dolichol
  • Oligo chain transferred to NH2 of Asparagine
  • 4 Sugars clipped off: ready for transport to Golgi
  • Further trimming/adding of monosaccharides occurs in Golgi
  • Glycoprotein complex complete.
106
Q

What is the pathology of Cystic Fibrosis?

A

Defect: Mutation in Cl- ion channel due to incorrectly folded protein.

Symptoms: Rales/crackling, rhonchi, clubbed fingers, thick and heavy secretions (problems with digestion and increased susceptibility of lungs to infection)

Diagnostics: Kiss the baby! (Axillary sweat test)

107
Q

Describe Bronchiectasis.

A

irreversible bronchial dilation and thickened bronchial walls

dilated central bronchi

hyperexpansion

(scarring from chronic expansion)

108
Q

What is the pathology of Hypercholesterolemia? (Familial)

A

Defect: Mutations in the LDL-Receptors

Symptoms: Xanthomata, Xanthelasmata, corneal arcus, atherosclerosis. Increased plasma cholesterol and LDL production

Note: ‘Normal’ mutation of LDL-R prevents it from binding with LDL, meaning it actually reaches the plasma membrane.

109
Q

What is the Class II mutation of LDL-R in Hypercholesterolemia?

A

LDL-R proteins are misfolded, meaning they never reach the plasma membrane to begin with.

110
Q

Give a general description of the Secretory Pathway.

A
  • Proteins enter ER from synthesis
  • Vesicle buds off ER and brings Protein to Cis-Golgi
  • Protein travels through cisternae of the Golgi
  • Vesicle buds off again from Trans-Golgi
  • Vesicle fuses with PM, secreting protein.
111
Q

What are COPII and COPI proteins?

A

They are proteins that form on the surfaces of the ER and Golgi membranes (respectively) that form the vesicles. They remain on the vesicle surface until it reaches its target destination.

112
Q

How are the vesicles moved to their targets?

A

Motor proteins on microtubules will carry the vesicles one way or another based on which direction they travel on microtubules.

113
Q

What about microtubules allows motor proteins to travel in their respective directions?

A

Polarity. Microtubules have + and - ends, and motor proteins will always travel from one to another based on their function.

114
Q

What are targetting signals? What is the default targetting signal?

A

Sequences on the protein that destine it for specific cellular targets.

The default is to have NO ER SIGNAL SEQUENCE.

  • if there are no other sequences on the protein, it just goes to the Cytosol
  • NLS -> Nucleus
  • SKL -> Peroxisome
  • Mitochondrial Signal Sequence -> WELL WHERE DO YOU THINK
115
Q

What happens to a protein with an ER signal sequence?(targetting sequences)

A
  • no other sequence -> rER -> PM/secretion
  • KDEL or KKXX -> ER
  • M6P -> lysosome
116
Q

How does the cell trigger Vesicle Coat Assembly? (What proteins are used?

A

G-Proteins (ARF/SAR) bind a GDP and then bind to membrane, where GEF (REMEMBER THIS ASSHOLE?) is waiting.

GEF will convert GDP to GTP, and the active G-Protein will be bound to adapter.

Now inner COP proteins (SEC) bind to cargo receptors and G-Proteins, attracting the COP coating proteins.

117
Q

What happens to the coating (not the outer COP coat) once the Vesicle has completely formed?

A

The coating falls off (due to hydrolysis of GTP). This exposes binding sites for motor proteins, and allows for eventual fusion with target membrane.

118
Q

What are the proteins involved in Vesicle docking?

A 
Rab effector (on target membrane)
Rab-GTP (on vesicle)

This is the first contact made between Vesicle and target membrane.

119
Q

What are the proteins involved in Vesicle Fusion?

A

v-SNARE (vesicular snare)
t-SNARE (target membrane snare)

SNARE proteins intertwine for fusion. Separate from fused vesicle/membrane and are recycled.

120
Q

What are the proteins that assist in TERMINATING Vesicle Fusion?

A

NSF/SNAPs

They help dissociate the v and t-SNARE proteins, allowing proper membrane fusion.

121
Q

What are the functions of the Golgi Apparatus?

A
  • Major site of carbohydrate synthesis (GAGs included)
  • Adds oligosaccharides to proteins and lipids
  • send protein to PM/secrete proteins
  • sends proteins to Lysosome (REMEMBER THE M6P SIGNAL SEQUENCE)
122
Q

What kind of cell would you find prominent Golgi?

A

Cells specializing in secretion (ex. Goblet Cells).

123
Q

Name the two models of movement of proteins through Golgi apparatus.

A

Vesicular Transport Model

Cisternal Maturation Model

124
Q

Describe the Vesicular Transport Model.

A

Golgi stacks are stationary with separate enzymatics.

Vesicles hop from one stack to another until they are ultimately transmitted to the PM (or other target membrane)

125
Q

Describe the Cisternal Maturation Model.

A

Golgi stacks move, and enzymes are transferred to previous stacks in the order. (They do the same thing?

Incoming vesicles form NEW CIS-FACE, stacks will move forward until TRANS-FACE breaks apart and heads to PM (or other target membrane).

126
Q

What is the ERGIC?

A

ER-Golgi Intermediate Compartment

tube clusters between ER and Golgi

127
Q

Where in the Golgi would the M6P tag/sequence be added to a protein?

A

In the Cis-Face of the Golgi.

128
Q

Which kind of glycosylation occurs in the Golgi?

A

O-linked glycosylation

N-linked oligosaccharide MODIFICATION might occur, but not glycosylation(??)

129
Q

What is the pathology of I-Cell Disease? (Mucolipidosis II)

A

Defect: deficiency of N-acetylglucosamine phosphotransferase
- THIS MEANS M6P TAG IS ABSENT

Symptoms: Distended inclusion bodies; these are lysosomes that don’t have any proper enzymes, so they build up stuff until they interfere with cellular function.)

Presentation: Coarse facial features, skeletal abnormalities (lack of growth), short life expectancy, psychomotor retardation

130
Q

What are the two types of Secretion? What’s the difference?

A

Constitutive Secretion - constant, unregulated membrane fusion.
- ECM components

Regulated Secretion - regulated membrane fusion that only commences once a specific signal has been received by the cell (hormone or neurotransmitter).
- secrete hormones, NTs, digestive enzymes.

131
Q

What would an intracellular signal be for Regulated Secretion be?

A

Increased cytosolic Ca2+ (from ECF or intracellular stores)

132
Q

How is the destination of Vesicles in secretion determined/

A

Constitutive: no signal in unpolarized cells, signal for apical vs. basolateral in polarized cells.

Regulated: Signal selectively groups proteins into secretory vesicle

133
Q

What do Epithelial Cells secrete on their Apical/Basolateral surfaces?

A

Apical: secrete digestive enzymes/mucus

Basolateral: secrete basal lamina

134
Q

How are proteins sent to Apical/Basolateral surfaces?

A

Apical: GPI-linked proteins and membrane proteins with long domain associate with glycosphingolipids and cholesterol in lipid rafts. This directs to the apical surface.

Basolateral: Proteins just have sorting signals.

135
Q

What is Transocytosis?

A

Process that involves both endo and exocytosis.

pH determines direction of process.

Receptor binds protein at a certain pH (lumen on one side of cell will have pH acceptable for binding), and then will endocytose receptor-protein complex. Then the complex will be sent to lumen on other side of cell, where the vesicle will fuse with the membrane and exocytose. The receptor will now release the protein into the other lumen (other lumen has pH unacceptable for binding).

136
Q

What happens to a Vesicle the longer it is active? How?

A

It gets smaller and more acidic; membrane must be recycled.

All vesicles have an H+ pump that pumps H+ into the lumen of the vesicle. Higher acidity allows cargo receptors to detach from the vesicles, recycling them, and also activates certain proteins.

137
Q

What are the proteins involved in Synaptic Vesicle Fusion?

A

v-SNARE: synaptobrevin
t-SNARE: syntaxin
Ca2+ sensors: synaptotagmin

NSF assists in dissociation of -brevin from -taxin

138
Q

What does Botulin toxin do? What pathology follows?

A

It cleaves the v-SNARE protein Synaptobrevin in neurons that transmit ACh at the NMJ.

It results in Flaccid Paralysis (Botulism: paralysis of resp/skeletal muscles)

139
Q

What does Tetanospasmin toxin do? What pathology follows?

A

It cleaves the v-SNARE protein Synaptobrevin in neurons that transmit GABA and glycine from upper motor neurons.

It results in Spastic Paralysis. (Tetanus: prolonged contraction of skeletal muscles)

140
Q

What is the spatula test?

A

Stick a spatula in the mouth to touch uvula/back of neck to stimulate gag reflex.

Normal: Gag reflex
Tetanus: Bite down on spatula.

141
Q

What are the three Endocytotic Mechanisms?

A

Pinocytosis
Phagocytosis
Receptor-mediated Endocytosis

142
Q

What is the primary difference between Pino/Phagocytosis and Receptor-mediated Endocytosis (RME)?

A

In Pino/Phagocytosis, the vesicle is formed by the cytoskeleton.

In RME, the receptor proteins cause the deformation that forms the vesicle.

143
Q

Describe Pinocytosis.

A

“Drinking”

  • ingestion of ECF
  • growth factors and other signals stimulate actin to remodel the cytoskeleton for vesicle formation
  • CONSTITUTIVE.

Vesicle = Pinosome

144
Q

Describe Phagocytosis.

A

“Eating”

  • ingestion of large particles, bacteria, and dead cells
  • performed by specialized cells
  • triggered by receptors, but independent of coating proteins that characterize RME. (Receptors bind Opsonins)

Vesicle = Phagosome/Phagolysosome
- phagolysosome is formed by fusing Lysosome with Phagosome, which contributes to degradation of foreign material.

145
Q

What is an Opsonin?

A

A component on a cell that is bound by receptors on a phagocytic cell for phagocytosis.

146
Q

What are the phases of Phagocytosis?

A

Attachment
- phagocyte binds to Opsonins
Engulfment
- actin filament assembly creates ‘cup’ around foreigner, eventually creates Phagosome
Fusion with lysosome
- Phagolysosome is formed (note that fusion proteins are involved. Ex. Rab, SNAREs, SNAP/NSF)
Digestion

147
Q

What is the difference between a primary and secondary lysosome?

A

Primary = brand-new, fresh off the Trans-Golgi press. Not yet digesting material.

Secondary = any lysosome that has degraded (or is currently degrading substrate). Various states of degradation.

148
Q

Describe the mechanism of RME

A
  • cargo protein binds to cargo receptor
  • Adaptin binds to membrane by receptors and v-SNAREs
  • Adaptin recruits and binds Clathrin, forming clusters of Adaptin-Clathrin.
  • Size of clusters will deform the membrane they’re bound to, which forms the vesicle.
  • At a certain point Dynamin will pinch the membrane off and form the vesicle.
  • Clathrin-Adaptin coat will fall off for reuse in next vesicle.
  • Rab GTPase binds (prep for fusion)
  • Vesicle will fuse to Early endosome (REMEMBER HOW FUSION WORKS? IT’S BASICALLY THE SAME THING)
  • Vesicle will eventually be recycled, along with v-SNARE proteins.
149
Q

What kind of structure does Clathrin have?

A

Triskelion (3 polypeptide chains form 3-legged structure)

150
Q

Recall Familial Hypercholesterolemia. What is the typical pathology and what are the Class II and IV pathologies?

A

Classic: LDL-R does not function properly
Class II: LDL-R does not reach the PM due to misfolding.
Class IV: LDL-R reaches PM but does not cluster properly (inefficient endocytosis)

151
Q

What are Caveolae?

A

“Little cavities” AKA invaginations in the PM. They are involved in the other RME process (Clathrin is the first).

152
Q

Name the protein involved in forming Caveolae and where they would typically form.

A

Caveolin protein.

caveolae will typically be found in lipid rafts

153
Q

How do you differentiate Caveolae from Clathrin Coated Vesicles?

A

Caveolae will have a spiked-coat morphology in comparison with Clathrin Coated Vesicles, which will hav ea noticeably darker inner layer with no spikes.

154
Q

What are contained in Lysosomes? What protects them from those contents?

A

Hydrolytic enzymes/acid hydrolases

Glycosylated membrane of the lysosome is thought to protect the lysosome from itself.

155
Q

What gets sent in a vesicle from the Trans-Golgi to an Endosome/Lysosome?

A

Lysosomal Enzymes only.

156
Q

What gets sent in a vesicle from the Endosome to the Golgi?

A

M6P receptors and recycled membrane only.

157
Q

What gets sent in a vesicle from the Endosome to the PM?

A

LDL-R only

158
Q

What gets sent in a vesicle from the PM to the Endosome?

A

Endocytotic substrate.

159
Q

What are the characteristics of a “Late” endosome?

A
  • Lower pH
  • More enzymes
  • Higher concentration (membrane is being recycled, remember?)

Note: Late endosome may become secondary lysosome(?)

160
Q

What are the three fates of a Vesicle that exits the Trans Golgi Network (TGN)?

A
  • Constitutive Secretion
  • Regulated Secretion
  • Lysosomal/Endosomal Pathway
161
Q

Once again, what must a protein be tagged with in order to be sent to a lysosome? Where does this tag get implemented?

A

M6P Tag

It is placed in the cis-Golgi.

162
Q

What is the enzyme responsible for placing M6P on the protein?

A

GlcNAc phosphotransferase

163
Q

Clathrin coating is only shown in what two pathways?

A

Movement of vesicles from TGN to Lysosome

Endocytosis

Note: Process for Vesicle budding off of TGN is essentially the same as endocytosis, just in reverse.

164
Q

How are lysosomal enzymes activated?

A

When they are transported to the acidic (early) endosome, the phosphate is removed so they can’t rebind to M6P, and the acidity of the endosome activates them.

165
Q

How are Endosomes/Lysosomes acidified? What is the purpose of this acidification?

A

Remember the H+ pump on all lysosomes? It’s called V-Type ATPase, and it pumps H+ into the endosome/lysosome

The acidity of the Lysosome is for degradation as well as detaching of cargo molecules from their receptors.

166
Q

Name the 3 pathways that lead to degradation in Lysosomes.

A

Endocytosis

Phagocytosis

Autophagy

167
Q

Describe the Endocytic pathway.

A
  • Endocytic vesicles are brought to Early Endosomes
  • Maturation of Early Endosomes to Late Endosomes occurs (Multivesicular Bodies, aka MVB)
  • MVBs gradually recycle vesicles back to PM and become Late Endosomes by fusing with each other/other Late Endosomes
  • Late Endosomes become Endolysosomes and Lysosomes by fusing with existing Lysosomes and Progressive Acidification

Note: MVBs break down unneeded TM receptors by exposing them to acidic interior when forming ‘vesicle’ inside itself.

168
Q

How is a protein destined to join MVB? What happens after?

A

It is given a mono-Ubiquitin tag.

This causes an invagination in the Endosome/MVB, which will allow Lysosomal Lipases to chew up the ‘interior vesicle’

169
Q

Describe Autophagy.

A

It is thought that the ER envelopes older organelles and fuses with a Lysosome for breakdown of all inner membranes.

Recall heavily glycosylated membrane of Lysosome offers protection from degrading.

170
Q

What are Residual Bodies? What are their two fates?

A

Material within the Lysosome that can degrade no further.

They are either Exocytosed or remain within the cell as pigmented lipids, called Lipofuscin.

171
Q

What is a cytological characterisitc of Tay Sachs disease?

A

In a ganglion cell, you will see prominent Lysosomes with ‘whorled’ configuration.

172
Q

What is a Gaucher Cell?

A

A cell with elongated, distended Lysosomes.

173
Q

Recall I-Cell Disease! What is its pathology?

A

Defect: Absense of M6P tag.

Symptoms: Symptoms: Distended inclusion bodies; this is due to acid hydrolases being secreted extracellularly (because no M6P tag)

Presentation: Coarse facial features, skeletal abnormalities (lack of growth), short life expectancy, psychomotor retardation

174
Q

What is a milder form of I-Cell disease?

A

Pseudo-Hurler Polydystrophy (Mucolipidosis III)

175
Q

What is a Mucopolysaccharidosis?

A

Defective degradation of GAGs.

MPS I - MPS VII

176
Q

Describe the pathology of Hurler Syndrome (MPS IH)

A

Most severe MPS
Defect: Deficiency of a-L-iduronidase (autosomal recessive)
- accumulation of dermatan sulphate and heparan sulphate

Symptoms: Normal growth up til a few months, then:

  • Physical/Mental deterioration
  • Hepatosplenomegaly
  • Coarse Facial Features
  • Hirsuitism
  • Corneal Clouding
177
Q

What are variants of Hurler Syndrome (MPS IH)? List them all in order of severity.

A

Scheie (MPS IS) and Hurler-Scheie (MPS IHS) Syndrome

There is residual a-L-iduronidase activity.

Severity: MPS IH > MPS IHS > MPS IS`

178
Q

Describe the pathology of Hunter syndrome (MPS II)

A

Defect: Deficiency of iduronodate sulphatase
- accumulation of dermatan sulphate and heparan sulphate

Symptoms: Similar to MPS IH EXCEPT:

  • later presentation/milder course
  • no corneal clouding
  • X-linked, not autosomal recessive
179
Q

Describe the pathology of Sanfilippo syndrome (MPS III).

A

Defect: can be various different enzymes
- problem with heparan sulphate degradatio (types A-D)

Symptoms: Normal development for 1-2 years, then:

  • mental retardation/behavioral disturbance
  • hearing loss
  • mild facial dysmorphism (NO HIRSUITISM)
  • progressive immobility, dysphagia, seizures and demenntia
180
Q

Check to see if you need to know the following:

A

MPS IV, VI, VII

181
Q

Describe Metachromatic Leukodystrophy.

A

Defect: deficiency of ARSA (autosomal recessive)

- defective degradation of sulfatides, which are toxic to nervous system. DESTROYS MYELIN.

182
Q

Describe pathology of Chediak-Higashi syndrome.

A

Defect: Mutation in CHS1/LYST (lysosome trafficking protein involved in vesicle fusion)

Symptoms: Hypopigmentation (autophagy of melanosomes in melanocytes)

  • Delayed fusion of phagosome with lysosome in leukocytes
  • granular defects in NK cells and platelets
183
Q

What is the function of Mitochondrial Cristae?

A

Increase surface area for machinery to attach

184
Q

Where do a majority of mitochondrial proteins come from?

A

They were encoded separately in nucleus, and are added to mitochondria post-translationally.

185
Q

What are the shapes and distributions of mitochondria? What about their cristae?

A

Most cells have mitochondria with Lamellar cristae:

  • Hepatocyte: oval with numerous cristae
  • Skeletal Muscles: rows nestled between myofibrils
  • Sperm: wrapped around flagellum

Steroid-secreting cells have mitochondria with Tubular Cristae

186
Q

What is the structural organization of a Mitochondrion?

A

Outer Membrane (permeable to small molecules/ions)
Intermembraneous Space
Inner Membrane (impermeable to most molecules and ALL ions)
- Cristae!
Matrix (produce ATP)

187
Q

What is the Inner Membrane of the Mitochondria impermeable to?

A

Ions.

188
Q

What is the component of the Inner Membrane that makes it impermeable to ions? Where is this component synthesized?

A

Cardiolipin.

It is manufactured in the Outer Membrane and is sent to function in the Inner Membrane.

189
Q

What are the functions of the three major Mitochondrial compartments?

A

Outer Membrane:

  • Cardiolipin synthesis
  • Lipid modification

Inner Membrane
- ETC/ATP synthase

Matrix
- Oxidative Metabolism

190
Q

What is the integral protein involved in the Outer Membrane? The Inner Membrane?

A

Outer Membrane: Porins
- free diffusion of small molecules and ions

Inner Membrane
- Transport proteins; impermeable to small ions.

191
Q

What special characteristic of Cardiolipin gives it is characteristic of impermeability?

A

It is a ‘double phospholipid’; it has 4 fatty acyl tails instead of 2.

192
Q

Describe Barth Syndrome.

A

Defect: Cardiolipin synthesis disorder (X-linked)

Symptoms: Cardiomyopathy, generalized muscle weakness and chronic fatigue, high mortality in infancy.

193
Q

Where is one place/process Mitochondria gets Acetyl CoA from?

A

Glycolysis in the cytoplasm. It yields pyruvate, which is shuttled into the mitochondrion and broken down into Acetyl CoA, a fundamental compound in the TCA cycle.

194
Q

How does the TCA cycle make use of Acetyl CoA?

A

It is used to reduce reduce NAD+ to NADH, which provides the ETC with high energy electrons it can use to produce ATP.

195
Q

What happens as electrons are moved across the ETC?

A

An electrochemical proton gradient is formed, also known as Proton-motive force. The Intermembrane space is more positive (more H+ because it’s being pumped in there by ETC) than the Matrix.

196
Q

What is the function of the Proton-Motive Force?

A

It provides a proton gradient that ultimately drives the ATP synthase at the end of the ETC cycle.

Protons will flow ‘down’ the gradient to turn the turbine (ATP Synthase). Mechanical energy of turning converts ADP + Pi to ATP.

197
Q

What else does the Proton-Motive Force drive? (Think of the various gradients it forms)

A

More positive outside than inside: drives ADP (3-)/ATP (4-) exchange

More acidic outside than inside: drives Pyruvate and Pi import.

198
Q

What is a function of Mitochondria that happens in babies but not really in adults?

A

Thermogenesis via mitochondria of Brown Adipose (lost by adulthood). Babies do not yet have shaking reflex, so must use this process to regulate temperature.

199
Q

How does Thermogenesis work?

A

An uncoupling protein (UCP), Thermogenin, forms a channel in inner membrane that levels out the Proton-Motive force/Electrochemical Gradient, UNCOUPLING the respiratory processes (ETC, TCA) from ATP synthesis.

Respiratory processes GENERATE HEAT.

200
Q

What damaging compound naturally from what processes in the Mitochondria?

A

Reactive Oxygen Species (ROS) are a natural byproduct of Oxidative Phosphorylation (ETC).

201
Q

What are the dangers of ROS?

A

Can inactivate ETC e- acceptors which build up more ROS.

  • damages protein, RNA, DNA
  • implicated in degenerative diseases (Alzheimers), cancer, aging.
202
Q

What are two antioxidants?

A

Glutathione peroxidase, superoxide dismutase

203
Q

What causes the intrinsic pathway of Apoptosis?

A

Chemo/Radiotherapy.

- Causes Caspase cascade (cytochrome c and Apaf-1), which triggers Apoptosis

204
Q

How is the intrinsic pathway initiated?

A

Cell damage/stress triggers Pro-Apoptotic bcl-2 proteins like BAD and BAX to move from cytosol to mitochondrial membrane, forming pores (BAX)

Pores release cytochrome c into cytosol, which triggers the Caspase Cascade.

205
Q

What are the anti-apoptotic bcl-2 proteins?

A

Bcl-2 protein (lol i still dun get)

206
Q

How do Mitochondria divide? When do they divide?

A

They divide via binary fission, and do so in response to energy needs of the cell, NOT IN RESPONSE TO CELL CYCLE.

207
Q

What contributes to variability of mitochondrial disease?

A

Heteroplasmy, aka how many affected mitochondria are randomly distributed to primary oocytes.

(Note Bottleneck Effect)

208
Q

Where do most Mitochondrial proteins come from?

A

Nuclear genes; translated fully in cytosol.

Bound by Hsp70 in cytosol to prevent complete folding, and is imported into mitochondria thanks to a Mitochondrial signal sequence.

209
Q

How is a Mitochondrial protein imported into the Mitochondria? (What are the 2 proteins involved)

A

TOM (Translocase of OM)
- recognizes signal sequence

TIM (Translocase of IM)

  • translocates protein across IM; requires proton gradient
  • Hsp70 of Matrix (not the same as cytosolic Hsp70) helps pull the protein in, much like BiP.
  • Once in cytosol, protein is allowed to fold.
210
Q

What are the functions of a Peroxisome?

A

Biosynthesis: Plasmalogen synthesis and alternative source of Cholesterol and Dolichol.

Degradation: VLCFA Beta-Oxidation and Purine Catabolism

Note: Also contains Catalases (peroxidases) that break down H2O2 resultant from oxidation reactions.

211
Q

What is the signal sequence responsible for sending a protein to the Peroxisome?

A

No ER Signal Sequence, SKL signal sequence present.

212
Q

How do Peroxisomes form?

A

They form from ER vesicles and/or pre-existing peroxisomes that undergo Fission.

Peroxins are receptors in Peroxisome membranes that import cytosolic proteins post-translationally, completing formation of Peroxisome.

213
Q

Describe Oxidase function vs. Catalase function.

A

Oxidase: use O2 to remove H atoms from organic substrates. Byproduct = H2O2

Catalase: Uses H2O2 to oxidize toxins (and also get rid of H2O2). Byproduct = 2 H2O per toxin molecule.

214
Q

Where else can VLCFA be degraded?

A

NOWHERE. Must degrade VLCFA’s in peroxisomes until their chains (>24) are reduced to around C10.

215
Q

What are the uses for Fatty Acid Oxidation? (VLCFA degradation)

A

Degradation of VLCFA is a source of metabolic energy and a source for Acetyl CoA (used for biosynth of cholesterol and bile acids).

216
Q

What are the products of Purine Catabolism?

A

A and G Nucleic Acids are degraded into xanthine and then into uric acid.

217
Q

What is the enzyme used to catalyze Purine Catabolism?

A

Xanthine Oxidase.

218
Q

What is the pathology of Gout?

A

Defect: Too much uric acid; builds up in joints.

Symptoms: Arthritis from Hyperuricaemia, noticeable swelling of digits in phalangeal joints.

Treatment: Allopurinol (xanthine oxidase inhibitor)

219
Q

Why is Plasmalogen synthesis in Peroxisomes so important?

A

Plasmalogen is responsible for a large chunk of myelination of nerves.

220
Q

Describe the pathology of Zellweger Syndrome.

A

Defect: Peroxins do not recognize SKL sequences (Autosomal recessive)
Note: Look familiar? IT SHOULD. THIS IS WHAT HAPPENS IN I-CELL DISEASE EXCEPT WITH LDL-R.

Symptoms: Peroxisome deficiency. Abnormal brain development due to too much VLCFA accumulating in glial cell membrane.

Prominent forehead, mental retardation.

221
Q

Describe the Pathology of XALD (X-linked AdrenoLeukoDystrophy).

A

Defect: problem with transportation of VLCFA into Peroxisomes.

Symptoms: VLCFA buildup in brain (myelin breakdown) and adrenal cortex (adrenal atrophy)

MCB Block 3 (4 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions