Cell Bio: Organelles

Front 1

ER Basics

Back 1

1. 10% of cell volume
2. Continuous through cell
3. ER membrane produces lipids and protiens
4. Enzymes attached to cytosolic surface use fatty acids to make phospholipids that flip (via flippase enzyme) to cisternal surface
5. Self replicating.

Front 2

Smooth ER (SER)

Back 2

1. Abundant in cells that detox molecules: Liver (cytochrome 450 in SER oxidizes drugs)
2. Abundant in cells that produce steroid hormones--SER makes cholesterol and synthesizes steroids) (adrenal gland)
3. in Sarcoplasmic reticulum where Ca+ is released to cause contractions

Front 3

Rough ER

Back 3

1. Has polyribosomes on surface that translate proteins of ER, Golgi, endosome, lysosome, plasma membrane, and cell exterior.

Front 4

Ribosomes

Back 4

1. Large and Small subunit that attach to mRNA to form polyribosome.
2. Free polyribosomes translate proteins of cytosol, mitochondria, and nuclei

Front 5

ER Signal Sequence

Back 5

1. 16-30 AA chain is made (signal sequence)
2. Signal Sequence binds to Signal Recognition Particle (SRP) on ER. SRP is released and translation begins.
3. Growing polypeptide passes through ER membrane into ER cisterna.
4. Signal Peptidase removes signal sequence. Protein folds.
~co-translational (post-translational are proteins translated on free ribosomes)
~misfolded proteins are exported to cytosol and broken down in proteasomes.

Front 6

Transmembrane Proteins on ER

Back 6

1. Have stop signal (alpha helix).
2. Signal Sequen is removed and protein stays.

Front 7

The Mighty Golgi and COPs transport

Back 7

1. Modifies, sorts, and packages proteins and lipids from ER.
2. COPII-coated vesicles transport from RER to cis Golgi.
3. COPI-coated vesicles --> transfer from Cis to medial to trans (antrograde)
4. COPI-Coated vesicles (retrograde) bring soluble ER residents and membranes back to golgi

Front 8

Clathrin-Coated vesicles and SNARES

Back 8

1. From or two trans golgi
2. Has receptor that binds cargo
3. Dynamin pinches off vesicle. Clathrin is removed.
4. V- SNARES direct vesicles to T - SNARES.

Front 9

Glycosylation in ER

Back 9

1. Oligosaccharde of 14 sugars is transferred from lipid dolichol in the ER membrane to asparagine on nascent protein as it inters ER.

Front 10

KDEL Signal

Back 10

1. ER resident retention signal.
2. If ER resident proteins enter Golgi, they bind to KDEL receptors and COPI returns the bad boys.

Front 11

Modifications in the Golgi (on Cis, Medial, and Trans)

Back 11

Cis Golgi: Sorting, phosphorylation
Cis Cisterna: Removal of Mannose
Medial Cisterna: Removal of Mann, addition of GlcNac
Trans Cisterna: addition of Gal, addition of NANA
Trans Golgi: sulfation of tyrosines, carbs, and more sorting

Front 12

Constitutive Secretion

Back 12

1. Golgi Products are discharged to cell surface and are immediately ushered out of cell. This can make the ECM fibers (collagen--strengthen and organize, Elastin--resilience, fibronectin--attach fibroblasts to the ECM, and Laminin--to attach epithelia to basal lamina).
2. Procollagen is modified after leaving cell into collagen.

Front 13

Regulated Secreation

Back 13

1. Golgi Products (ex: insulin) are stored in secretory vesicles which are released rapidly in response to hormone or neural stimuli.
2. Packaged on trans and sorted into vesicles where contents can be proteolytically processed.
3. Vesicle membrane proteins may be recycled by endocytosis or remain apart of membrane (ion channels in apical surface of epithelial cells)

Front 14

Leishmania Parasite

Back 14

1. Use phagocytosis to enter cell where it blocks fusion to lysosomes

Front 15

Phagocytosis

Back 15

1. Cell engulfs entire cells or parts of cells. ex: white blood cells

Front 16

Receptor-mediated endocytosis

Back 16

1. Uptake of specific molecules (ligands)
2. Possible fates for molecules in cell: terminate in lysosomes, remain in cytoplasm, pass unchanged through cell (transcytosis)
3. Recycling of receptors is important for cellular uptake of ligand. Low pH removes receptor.

Front 17

How Lysosomes Destroy

Back 17

1. Contain 40ish enzymes to digest endocytosed material. Protected by glycosylation.
2. pH is about 5 and maintained by protein pump
3. Digest molecules that enter by receptor mediated endocytosis and digest cells and cell fragments by phagocytosis.
4. Can be stained because phosphatase precipitates in lead.

Front 18

Lysosome synthesis

Back 18

1. Translated on RER. Oligosaccharides are added in ER cisterna.
2. Arrive at cis Golgi, enzymes add M6P.
3. At trans Golgi, M6P binds to transmembrane M6P receptors and clathrin coated vesicle forms w/lysosomal enzymes.
4. Fuses with endosome, phosphate group is removed (prevents reattachment to M6P receptors; M6P are removed because of low pH receptors are recycled)
5. If lysosome fuses with plasma membrane, enzymes attach to M6P and are re-routed.

Front 19

Tay-Sachs Disease

Back 19

M6P doesn't direct lysosomal enzyme to lysosome ad lysosome doesn't destroy ganglioside. Resulting in ganglioside build up in brain.

Front 20

Silica and Asbestos fibers

Back 20

End up in lysosome and puncture its membrane.

Front 21

Perosixomes

Back 21

1. Contain enzymes that produce hydrogen peroxide by oxidizing substrate and a catalase that breaks down excess hydrogen peroxide into water and oxygen. Carries out beta oxidation of fatty acids into acetyl CoA
2. Found in liver to detox drugs and alcohol
3. Arise from RER and import proteins synthesized on free polyribosomes.
4. Capable of division, do not have nucleic acids

Front 22

Lysosomal Storage Disease

Back 22

Build up of substrate because enzymes are not appropriately targeted to lysosome or if lysosomal enzymes are defective.

Front 23

Inclusion-Cell (I-cell) disease

Back 23

1. Inherited
2. Caused by deficiency of enzyme that is responsible for phosphorylating mannose on M6P in golgi. Without M6P to target enzyme to lysosomes, enzymes are transported from golgi to extracellular fluid.
3. Accumulation of mucolipids and mucopolysaccharides results in large intracellular inclusions which manifest in coarse facial features, skeletal abnormalities, and mental retardation.

Front 24

Zellwegers Syndrome

Back 24

1. Lack key enzymes that lead to accumulation of toxic molecules, hepatomegaly, and high levels of iron and copper in blood. Fatal during infancy
2. Perixosome

Front 25

Neonatal Adrenoleukodystrophy

Back 25

1. Long chain fatty acids cannot be oxidized (beta oxidation proteins are not imported) and accumulate in brain, destroys myelin sheaths and in adrenal glands cause deficiency of adrenal steroid hormones. Fatty acids are found in CNS.
2. Perixisome disease

Front 26

Mitochondria Basics

Back 26

1. mt DNA lack histones, maternally inherited
2. Encodes 37 genes, including 13 subunits of OXPHOS in inner mitochondrial membrane.
3. Chaperon proteins (cytosolic Hsp70 and Mitochondrial Hsp70) control folding

Front 27

Inner Mitochondrial Membrane

Back 27

1. Invaginates to form cristae.
2. Contains enzymes to oxidize reactions.

Front 28

Mitochondrial Matrix

Back 28

1. Contains: TCA cycle, enzymes for oxidation of pyruvate and fatty acids, mtDNA, ribosomes, and tRNA.

Front 29

Intermembrane Space

Back 29

Where protons accumulate

Front 30

Mitochondrial Proteins from Nuclear DNA

Back 30

1. Coded by nuclear genes and translated on cytosolic polyribosomes.
2. Associate with hsp70 chaperon. Prevents folding and helps import
3. Signal sequence binds to the receptor on mito membrane.
4. Chaperon is released while ATP and proton gradient imports protein into IMM.

Front 31

Mitochondrial Ribosomes

Back 31

1. Smaller than cytosolic ribosomes
2. Similar to some prokaryotes and thus sensitive to Chloramphenicol (CAP and insenstive to cycloheximide (CH).

Front 32

Heteroplasmy

Back 32

1. Mitochondrial respiratory chain diseases caused by damage to nuclear DNA-encoded or mt DNA encoded proteins involved in OXPHOS.
2. Some mitochondria have normal DNA, while others have damaged.
3. If not enough good mitochondria to support ATP synthesis, cell dies.

Front 33

Leber's Hereditary Optic Neuropathy

Back 33

1. NADH dehydrogenase is normally located in IMM and removes high energy electrons from NADH.
2. Base substitution changes histidine to arginine in NADH dehydrogenase, blocking electron transport resulting in ATP blockage.

Front 34

Lysosomal Storage Disease: Lipid Storage Disorders

Back 34

Gaucher's and Neimann-Pick

Front 35

Lysosomal Storage Disease: Gangliosides

Back 35

Tay-Sachs

Front 36

Lysosomal Storage Disease: mucopolysacchariesoses

Back 36

Hunter Syndrome and Hurler Disease