Term
| What are the basic characteristics of Lysosomes? |
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Definition
Filled with about ~40 acid hydrolases
Proteases, nucleases, lipases, phospholipases, phosphatases, sulfatases
Require acidic environment; pH 4.5–5
H+ pump inside to maintain low pH
Reverse of ATP Synthase
Heavily glycosylated membrane |
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Term
| What are Primary lysosomes? |
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Definition
Bud from TGN, contain newly synthesised acid hydrolases
Not yet acquired material to be digested
Vesicle that is NOT YET DIGESTING |
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Term
| What are Secondary lysosomes? |
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Definition
Fusion of primary lysosome with substrate to be degraded
In various stages of degradation
Vesicle IS DIGESTING |
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Term
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Definition
| Become progressively more acidic. With increased activation you get increased enzymatic activity, continued digestion. |
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Term
| Late endosomes contain what? |
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Definition
Late endosomes contain material from endocytosis & hydrolytic enzymes
Become lysosome when most material degraded. Can reenter the system by fusing with another late endosome |
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Term
| Lysosomal sorting tag M6P are attached to Lysosomal proteins (acid hydrolases). Where so these proteins come from and where do they go? |
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Definition
| TGN to early / late endosome (M6P lysosomal sorting tag) |
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Term
| Vesicles with material to be degraded / released (ie: endocytosis); |
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Definition
| → early endosome → late endosome → lysosome |
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Term
| Where and by what is the Mannose-6-Phosphate put on the lysosomal proteins? |
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Definition
Put on in CIS GOLGI BY N-ACETYLGLUCOSAMINE PHOSPHOTRANSFERASE
NAG-PT |
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Term
| How does NAG-PT N-ACETYLGLUCOSAMINE PHOSPHOTRANSFERASE know to add M6P? |
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Definition
There is a signal in hydrolase for it
Cleavage in RER leaves mannose side chains 3 CHOs removed (glucose) |
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Term
| N-linked Oligosaccharides are what?, put on lysosomal protein where? and transferred from what? |
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Definition
| N-linked (ASPARAGINE RESIDUE) oligosccaharide chains put on in rER; transferred from dolichol |
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Term
| How to these damn lysosomal vesicles Budd from TGN? |
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Definition
There are M6P receptors on the trans Golgi Network.
- The Lysosomal proteins with the M6P tag bind to these recepors.
- The receptors have an adaptor protein attached to it.
- The M6P tag attaches to the receptor
- This attracts clathrin protein to cover the membrane...then u got your coat! |
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Term
| What is the Transport of hydrolases to lysosomes? |
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Definition
Cargo binds to M6P Receptor
M6P Receptor clusters, with adaptors, clathrin buds off vesicle
Clathrin coat removed & fusion with acidic endosome
Acid dissociates cargo from M6P receptor
Phosphate removed from cargo so can not rebind to M6P receptor
M6P Receptors recycled to TGN |
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Term
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Definition
| Low pH in endosome causes enzymes to become active AND dissociation of cargo!!! |
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Term
| Name some hydrolytic enzymes (=acid hydrolases) |
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Definition
These are active in acidic conditions
Nucleases
Proteases
Glyosidases
Lipases
Phosphatases
Sulfatases
Phospholipases |
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Term
| What are the 3 ways to degradation in lysocomes? |
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Definition
1. Phagocytosis
2. Endocytosis
3. Autophagy-double membrane around the organelle. |
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Term
Pathways to the Lysosome
What is Phagocytosis? |
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Definition
Digestion of macromolecules; ingestion of other dying cells or larger extracellular material
Opsionization
Non-specific |
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Term
Pathways to the Lysosome
What is Endocytosis? |
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Definition
Receptor proteins recycled from the cell surface
SPECIFIC |
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Term
Pathways to the Lysosome
What is Autophagy? |
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Definition
| Old or unneeded organelles or proteins in the cytoplasm |
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Term
| What are the Phases of Phagocytosis? |
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Definition
After a phagocyte ingests a microbe, it becomes a "phagosome"
Fusion of the phagosome with a lysosome forms a phagolysosome
Now that the lysosomal enzymes are there, digestion of ingested microbe occurs by enzyme.
Formation of RESIDUAL BODY containing indigestible material.
Discharge of waster materials by by exocytosis, or accumulation in cytosol as lipofucin |
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Term
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Definition
| contains indigestible material from fusion of a lysosome and phagosome. |
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Term
| What happens to late endosomes to become endolysosmes & lysosomes? |
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Definition
Late endosomes become endolysosmes & lysosomes by
1.Fusing with preexisting lysosomes
2. Progressive acidification |
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Term
| What is the Endocytic pathway: PM to lysosomes? |
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Definition
- Proteins destined to join MVB get a mono-ubiquitin tag
- Invagination of the endosome becomes the MVB
Combines with primary Lysosome that contains lysosomal proteases and lipases.
(lysosomal lipases completely chew up interior vesicle)
- The point of all of this is to downregulate receptors. |
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Term
| Going from LATE ENDOSOME TO ENDOLYSOSOME TO LYSOSOME there is an increase in hydrolytic activity. How? what is happening? |
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Definition
| PROGRESSIVELY MORE ACIDIC FROM LATE ENDOSOME TO ENDOLYSOSOME TO LYSOSOME VIA V-TYPE ATPase!!!!!! |
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Term
| What are the stages of Receptor-mediated endocytosis? |
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Definition
Vesicles leaving TGN (carrying acid hydrolases) fuse with an endosome
Vesicles from the plasma membrane fuse with early endosome which fuses with / becomes late endosome
Maturation of the late endosome creates the lysosome |
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Term
Receptor-mediated endocytosis of LDL
STEPS: |
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Definition
-The LDL comes and binds the LDL Receptor
These receptors have those adaptins which attract the clathrin proteins
-Clathrin coat forms as endocytosis keeps going and finishes.
-Once inside the cell you have uncoating of the clathrin coat.
-The naked vesicle fuses with the endosome (early)
NOTE: here the receptors can either be recycled or if it was another pathway the receptors would be destroyed
- Progressive acidification
Digestion
Cholesterol Released
- Lysosome is formed with the hydrolytic enzymes ready to eat up the coat holding the cholesterol.
-Free cholesterol is released. |
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Term
| What are the possible causes of Familial hypercholesterolemia? |
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Definition
Possible causes:
-mutation in LDL receptor, no clustering, no correct folding, no binding, no transport, no recycling, etc |
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Term
| Describe what happens in Familial Hypercholesterolemia: |
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Definition
| • Familial Hypercholesterolemia: defective LDL-R (doesn’t make it to membrane)(class II)→ LDL can’t be taken up from the plasma (blood) so stay in circulation → premature atherosclerosis, corneal arcus, xanthomata (cholesterol lumps in tendons), xanthelasmata (cholesterol lumps under skin) |
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Term
| What are the step of Authophagocytosis? |
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Definition
ER envelopes old organelles (ie: mitochondria)
→ double-membraned vessel enclosing organelle(s)
Fusion with a lysosome
lysosomal lipases break down all inner membranes; |
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Term
| During phagocytosis, how is the lysosomal membrane protected? |
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Definition
| lysosomal membrane protected by heavily glycosylated proteins & lipids |
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Term
| In Autophagy, we can also have what with a phagosome? |
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Definition
Phagosomes & autophagosomes fuse with primary lysosomes
→ autophagolysosome: digestion |
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Term
| There are two destinations for autophagocytosis: |
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Definition
Released as a residucal body..Can become lipofuscin “age pigment” OR
Exocytose from the cell– do u know what does this??? |
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Term
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Definition
Lipofuscin = pigmented lipids (“age pigments” accumulate in multiple organs)
Mainly LIVER |
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Term
| Lysosomal storage diseases |
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Definition
Defects in lysosomal hydrolases
Recessive
Most affect an individual hydrolase |
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Term
| What happens in lysosomal storage diseases? |
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Definition
Accumulation of partially degraded insoluble metabolites in lysosomes
→ enlarged lysosomes, interfere with normal cell function |
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Term
| What is the Most severe Lysosomal storage diseases? |
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Definition
Most severe = I-cell disease (inclusion cell disease);
almost all hydrolytic enzymes missing from fibroblast lysosomes
Undigested substrates accumulate → large inclusions in cells. |
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Term
| What does the Lost of Function in Enzyme B do/cause? |
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Definition
| LOF in Enzyme B causes you to not be able to further digest, enlarged lysosomes -> issues. |
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Term
| Ganglion in Tay Sachs...have.... |
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Definition
Have Prominent lyosomes with whorled configuration
Defect: GM2 ganglioside
Hexosaminidase A
“cherry-red” macula |
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Term
| Gaucher cell is a Lysosomal storage diseases that has.... |
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Definition
Elongated distended lysosomes
Defect: glucocerebrosidase |
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Term
| What are the 4 types of Lysosomal storage diseases? |
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Definition
1. Mucopolysaccharidoses (accumulation of sulfated polysaccharides / GAGs)
- Storage of disaccharides that cannot be broken down!
2. Lipid storage disorders / Sphingolipidoses (accumulation of sphingolipid)
3. Mucolipidoses (accumulation glycoprotein & glycolipid)
4. Leukodystrophies |
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Term
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Definition
| Glycos-amino-glycans[1] (GAGs) or mucopolysaccharides[2] are long unbranched polysaccharides consisting of a repeating disaccharide unit. |
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Term
| What is Mucopolysaccharidoses? |
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Definition
accumulation of sulfated polysaccharides / GAGs
Hunter syndrome
Hurler syndrome
Sanfilippo syndrome
Morquio syndrome
Maroteaux-Lamy syndrome
Sly syndrome |
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Term
| What are Lipid storage disorders / Sphingolipidoses? |
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Definition
accumulation of sphingolipid)
Gaucher's disease (accumulation of glucocerebroside)
Niemann-Pick disease (accumulation of sphingomyelin & cholesterol)
Gangliosidoses; Tay Sachs disease (GM2 gangliosidosis) |
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Term
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Definition
accumulation glycoprotein & glycolipid
I : sialidosis
II: I-cell disease
III: pseudo-Hurler polydystrophy (milder form of I-cell disease) |
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Term
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Definition
Mucolipidoses (accumulation glycoprotein & glycolipid)
I : sialidosis
II: I-cell disease
III: pseudo-Hurler polydystrophy |
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Term
What is Pseudo-Hurler Polydystrophy?
Mucolipidosis III |
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Definition
Partial Function of enzyme (N-acetylglucosamine phosphotransferase)
Some get M6P tag, some do not, hence why it is milder, but still develop symptoms
Milder form of I-cell disease |
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Term
| What are Mucopolysaccharidoses? |
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Definition
ACCUMULATION OF DISACCHARIDES!!!
Defective degradation of GAGs (mucopolysaccharides)
MPS I – MPS VII |
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Term
What is Scheie & Hurler-Scheie syndrome
(MPS IS & MPS IHS)? |
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Definition
Residual α-L-iduronidase activity!!
Milder disease (Scheie = mildest MPS I) |
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Term
| What is Sanfilippo syndrome (MPS III)? |
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Definition
(Hurler = most severe MPS but children with Sanfilippo live longer with more severe behavioural problems)
Defect in heparan sulphate degradation (types A-D) |
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Term
| What is Morquio syndrome (MPS IV)? |
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Definition
Defective degradation of keratan sulphate
Deficiency of:
Galactosamine-6-sulphatase (MPS IV A)
β-galactosidase (milder) (MPS IV B)
Short stature
Pectus carinatum (pigeon chest)
Normal IQ |
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Term
What is Maroteaux-Lamy syndrome (MPS VI)?
What is Sly syndrome (MPS VII)? |
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Definition
Similar to Hurler but normal IQ
different mutations |
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Term
Specialised lysosomes
Defects in melanosome exocytosis |
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Definition
Melanocytes produce & store pigment in melanosomes (= specialised lysosomes)
→ hypopigmentation |
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Term
Pigment taken up by keratinocytes
Melanosomes can fuse with PM, releasing pigment into extracellular space of dermis by exocytosis |
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Definition
| → Normal skin pigmentation |
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