Biology 266: Unit 1

What does the endoplasmic system consist of?

- Endoplasmic Reticulum

- Golgi Complex

- Endosomes

- Lysosomes

- Vacuoles

What is the primary function of the endoplasmic system?

A network in which materials are shuttled back and forth

how is material transported in the endoplasmic system?

Transport vesicles, which then fuse into the membrane if the acceptor

What does the ER consist of?

Network of interconnected internal membranes that extend from the nuclear membrane throughout the cytoplasm

What is the ER Lumen?

internal compartment of the ER

What percent of the cell membrane is the ER membrane?

50%

What is the general function of the Rough ER?

Ribosomes bound to the rough ER synthesize proteins to be secreted and also used by most of the cell's organelles

Which organelles within a cell use proteins synthesized by the rough ER

The ER itself, Golgi, Lysosomes, secretory vesicles, plasma membrane

Around half of the proteins are _________within the ER by covalent attachment of sugars (amino acids etc)

glycosylated

Where do proteins synthesized on free ribosomes in the cytosol remain/ move to?

Nucleus, mitochondria, chloroplast, peroxisomes

what is the general function of the smooth ER

The synthesis of lipids (fatty acids, chlotoesterol, phospholipids)

The smooth ER makes a major contriubution to _____________of all organelles by producing most of their _________

lipid composition of membranes, Lipids

What is the specialized function of the Smooth Er in endocrine cells?

Synthesis of steroid hormones

What's the specialized function of the smooth ER in liver cells?

Detox of various organic compounds

Whats the specialised function of the smooth ER in muscle cells?

sequestration of Ca ion from cytoplasm of muscle cells

General Function of the Transitional ER

A region of the ER where secretory Vesicles exit the ER en route to the golgi apparatus

Both _____and ______ are exported from the ER in transport vesicles.

proteins and Lipids

Where do vesicles in the ER bud from

the transisitional ER

After budding , vesicles carry their cargo first to the ...

ER - Golgi intermediate compartment (ERGIC)

What is the final destination of the vesicles originating from the transitional ER?

Golgi apparatus

what is the general function of the quality control in the ER once a protein has entered this origanelle?

Monitor proper folding of protein

what are the steps of quality control in ER (if a fold is achieved)

0. Glycosylation in the ER

1. Glucose residues are removed, leaving 1 Terminal Glucose

2. Protein associates with chaperones such as calnexin

3. Termincal glucose removed - attempt to fold

What are the steps of quality control that occur when the protein does not fold for the FIRST TIME

4. Enzyme UGGT adds the glucose back

5. Refolding attemped

6. Transported to the next compartment

What are the steps of quality control that occur when the protein does not fold SEVERAL TIMES

1. More sugars like mannose are rmoved

2. Protein is dislocated from the ER to the cytoplasm to be degraded by the proteasome (ER- associated degradation (ERAD))

What degrades the proteins after several failed folding attemps by the ER

Proteasome

What removed the glucose residue

glucosidase 1 and 2

What happens if too many unfolded proteins accumalate in the ER

Unfolded protein response (UPR)

- Stops translation

- Degrades misfolded proteins

- produced more chapersones

Prolonged ____ leads to apoptosis

UPR

What Golgi apparatus made of

Flattened membrane enclosed sacs (cisternae) and associated vesicles

Where is the golgi located

near the cell nucleus

What are the three functions of the Golgi

1. A factory in which proteins received from the ER:

a) are further glycosylated

b) sorted for transport to their eventual destinations:

- Lysosomes

- The plasma membrane

- Extracellular medium

2. Syntesization of some lipids including glycolipids and sphingomyelin

3. In plant cells, Golgi serves as the which the complex polysaccharides of the cell wall - Hemicellusloses and pectins are synthesisized

What are the five functionally distinct compartments of the Golgi (in order from top to bottom)

1 - Cis golgi network

2 - cis compartment of the golgi stack

3 - medial compartement of the golgi stack

4 - trans compartment of the golgi stack

5 - trans golgi network

Each golgi stack has 2 ____________,

1-

2-

Distinct faces

1. Cis - Entry - adjacent to the ER

2. Trans - Exit - towards the plasma membrane

Describe the movement of proteins within the golgi apparatus

1 - Proteins and lipids enter the cis golgi network in transport vesicles from ER

2- Proteins + lipids progress through the golgi stack in order: Cis, Medial, Trans

3 - Proteins + Lipids move into the trans golgi network which sorts/distrubites/directs traffic to lysosomes, plasma membrane,cell exterior

Where do proteins and lipids get sorted to in the trans golgi network (3)?

1 - Lysosomes

2 - Plasma Membrane

3 - Cell exterior

What are the 2 methods of movement for proteins within the GOLGI

1 - Vesicular Transport

2 - Cisternal Maturation

What is vesicular transport?

Cargo is shuttled from the CGN to the TGN in vesicles

enzymes work their magic and cargo is then shipped out

students (cargo) move from class to class to see different professors (enzymes)

What is cisternal maturation?

Cisternae (cargo) become the next type (they "mature"), and vesicles move backwards (trans to cis)

What are lysosomes and what do they contain?

Small membrane bound organelles; contain 50 different degradative enzymes : hydrolases

what do the degradative enzymes break down is lysosomes

Nucleic acids (nucleases) ,proteins ( proteases ) , Lipids (lipases) , Carbohydrates ( glycosidases )

All lysosomal enzymes are____?

acid hydrolases

What pH are acid hydrolases active in?

5

What pH are acid hydrolases inactive in? where is this pH characteristcally found?

7.2 - Cytosol

How is the lysosome's acidic pH maintained ?

an H+ (proton) ATPase in the membrane pumps protons into the lumen

What is the lumen?

central blood-filled space of a vessel

what shields the membrane of the lysosome from its degradative enzymes?

the integral membrane proteins are highly glycosylated

T/F: Lysosomes are consistenely the same size

False!

They are morphologically diverse organelles that are definded by their common function of degrading intracellular material

How can lysosomes vary in size/shape?

this may occur as a result of differences in the material that have are being degraded

what are primary lysosomes?

roughly spherical and do not contain obvious particulate or membrane debris

what are secondary lysosomes?

they are large and irregulary shaped as a result of fusion of the primary lysosomes with membrane engulfed aged and defective orgamelles : also contain particles of membranes in the process of being digested

why are secondary lysosomes deformed?

they have fused with primaries that have membrane engulfed organelles that are aged and defective: also contain particles of membranes in the process of being digested

what do secondary lysosomes contain?

contain particles of membranes in the process of being digested (autophagy)

what is an example of autophagy

mitophagy

What is mitophagy?

Form of autophagy that specifically targets and degrades defective mitochondria

what can autophagosomes contain? (3)

- Organelles

- Cytosolic proteins

- lipids

what are the three pathwayds for delivering materials to lysosomes?

1 - the digestion of molecules taken up from outside the cell (ENDOSYTOSIS)

2 - the digestion of large particles (bacteria, cell debris, ages cells from outside the cell) by phagosytsosis

3 - the digestion of aged or defective organelles by autophagy

What is phagosytosis?

Cell eating, essentially

example of phagocystosis

bacterium is "swallowed" by the cell and a membrane forms around it then delivered to the lysosome

example of endocytosis

"swallow" molecules then deliver to lysosome

example of autophagy

mitochondrial life span is only 10 days, thus a membrane begins to surround mitochondria forming an autophagosome and fuses with a lysosome for degradation

what is responsible for more than 30 human different genetic diseases?

mutations in the genes that encode lysosome acid hydrolases

what occurs when lysosome acis hydrolases are mutated

undegraded material accumulates within the lysosomes of affected individuals, hence the name Lysosomal Storage Disease

What kind of disease is Gacher's Disease

a lysosomal storage disease

how does gaucher's disease occur

mutation of the lysosomal enzyme required for the hydrolisis of glycolipid hlucocerbroside to glucose and ceramide

what can be used to treat gaucher's disease?

Cerezyme

what does cerezyme do to fight against gaucher's disease?

Cerezyme is a modified form of glucocerebrosidase - which is taken up my endocytosis and delivered to the lysome alloing the hydrolisis to occur

what are 2 ways to treat lysomal storage diseases

1 - using endocytosis of similar enzymes since endosomes end up fusing with lysosomes

2 - inhibiting production of the accumilating substance

in gaucher's case wed inhibit the production of glucocerebrosidase

What do peroxisomes do?

site of synthesis and degradation of hydrogen peroxide (H2O2) very toxic

how is hydrogen peroxide produced in peroxisomes?

oxidation of RH2 and O2 into H2O2

What helps break hydrogen peroxide into water and oxgen

catalase

what does h2o2 break down into?

water and o2 with the help of catalse (2H2o2)

what are the functions of peroxisomes (4)?

1 - Oxidation of very long fatty acid chains (16 or more)

2 - Decomposition of hydrogen peroxide (into water and oxygene)

3 - bisyntehsis of plasmamalogens (lipid in myelin)

4 - Conversion of stored fatty acids to carbs in germinating seeds of plants (provides energy for growth - glyoxosome)

what does the oxidation of very long chain fatty acids lead to?

production of hydrogen peroxide - NOT LINKED TO ATP FORMATION

What are three similarities between peroxisomes and mitochondria?

1 - both formed from a pre existing organelle (divide by fission)

2 - both import preformed proteins from the cytosol

3 - both oxidize fatty acids

where do peroxisomes import from

directly from cytosol

Mitochondria may even form ___________ that carry _______ to peroxisomes

vesicles, material

what are difference between mitochondria and peroxisomes? (2)

1 - Mitochondria have 2 bilayers, peroxisomes have but 1

2 - peroxisomes do not contain DNA/ribosomes but mitochondria do

what are 2 peroxisomal disorders?

1 - Zellweger syndrome

2 - X - Linked adrenoleukodystrophy

What is Zellweger syndrome?

Patients CAN synthesze peroxsimal enzymes but CANNOT import them into the organnell - appear as ghosts

what is a conseqeunce on the brain of the zellweger syndrome?

lack of myelin!!

what is X- linked adrenoleukodystrophy (X -ALD )

inability to import long chain fatty acids which accumilate and impair the myelin

how has X- linked adrenoleukodystrophy (X -ALD ) been treated?

gene therapy ( adding back a functional VLCFA transporter)

What is the cytoskeleton?

network of protein filaments extending throughout the cytoplasm

what are the functions of the cytoskelaton

1 - provides the structural framework of the cell:

- determines cell shape and general orientation of cytoplasm

2 - Responsible for movements of entire cells, organelles, transport vesicles, chromosomes during cell division

what are the three main kind of cytoskeletal filaments?

1 - Microtubule

2 - Actin Filaments

3 - Intermediate filaments

what are microtubules built of

protein tubulin

what is the diameter of microtubules

25 nm

What do microtubules help in?

Intracellular transport, cell division, cell organization

what are actin filaments made of

protein actin

what is the diameter of actin filaments?

8nm

what do actin filaments help in

mobility and muscle contraction

what is the diameter of intermediate filaments?

10 nm

what are intermediate filaments made of?

70 different proteins - some being tissue specific

what do intermediate filaments help with?

provide structural support and mechanical strength

What does the nuclear envelope consist of? (3)

1 - 2 concentric membranes (inter and outer nuclear memb.)

2 - nuclear lamina

3 - Nuclear pore complexes

What is the nuclear lamina?

a fibrous network that provides structural support to the nucleus (a bunch of proteins)

NPC are the only ________through which _________ are able to travel between the nucleus and the cytoplasm

Channels, molecules

what does the nuclear lamina support?

nuclear envelope

what is the nucleur envelope consist of?

Lamins

what is the integreity of the nuclear lamina regulated by?

phosphrylation & dephosphorlation