Lysosome

Question 1

Describe lysosomes

Answer 1

Primary site of intracell digestion. Full of hydrolytic enzymes (M6P tag) activated by pH = 4.5-5 (includes proteases, nucleases, lipases, phospholipases, phosphatases, sulfatases). Two types of lysosomes. Formed form late endosomes

Question 2

What are the types of lysosomes

Answer 2

Primary = Bud from TGN contains newly synthesized hydrolases with no material to digest
Secondary = Fusion of primary with substrate, includes all various stages of digestion

Question 3

Describe evolution of endosome

Answer 3

Late endosome cotains material from endo and H-lytic enzymes and becomes lysosome when most material is degraded as acidity increases

Question 4

Describe M6P tag transfer to lysosome

Answer 4

N-linked oligo chains put on in rER (from dolichol). Signal in hydrolase for adding M6P: cleavage in rER leaves mannose side chains and M6P put on in cis-golgi by GlcNAc phosphotransferase causing M6P to have greater affinity for M6P-R in TGN

Question 5

Describe packaing in TGN

Answer 5

Clathrin coat (triskelion) 36 polyhedral. Inner layer to adaptins

Question 6

Describe acidification of Endo and Lys

Answer 6

H-lytic enzymes need activation in acidic enviroment. V-type ATPase in membrane pumps H into lys (needed for cargo/receptor detach as well). Lys membrane heavily glycosylated to protect

Question 7

What are the three degradation pathways

Answer 7

Phagocytosis, endocytosis recycling, autophagy

Question 8

Describe Phagocytosis

Answer 8

Chemotaxis and adherence of microbe to phag - phagosome - fusion with lys - digestion - residual body - discharge by exo or accumulate as lipofucin

Question 9

Describe Endocytosis Recycling

Answer 9

Maturation of early endo to late endo via MVBs which shed material to PM. To late endo by fusion with lysosome or progressive acidification. Down regulate by ubiq tag to invagination to lys lipases (downreg of LDL-R)

Question 10

Describe Autophagy

Answer 10

ER envelopes old organelle (2x memb) to lys to lys lipases

Question 11

What are lysosomal storage diseases

Answer 11

Defects in hydrolases (recessive) leading to accumulation of insoluble metabolites in lys leading to cell functional defect

Question 12

What is mucopolysacchyridosis (MPS)

Answer 12

Defect in degrade of GAGs, most recessive besides Hunters. Symptoms: course facial features, can have corneal clouding, joint stiffness and deform, hepatosplenomegaly, M retard, Hirsutism, Arterial deposits, urinary excretion of GAGs

Question 13

Define MPS1 (Hurlers Syndrome)

Answer 13

Defect in aplha-L-iduronodide sulphatase - accumulate dermatin and heparin sulphate normal symptoms. Milder is Scheoic with L-activity

Question 14

MPS2 (hunter)

Answer 14

X linked defect in iduronodide sulphatase leading to accumulation of DH sulphate similar to Hurlers but with no corneal clouding

Question 15

MPS3 (Sanflippo)

Answer 15

Hep sulphate degradation with normal until 2 years than progressive mental degradation and behavior changes

Question 16

MPS4 (Morquio)

Answer 16

Keratin sulphate defect with two variations: Galactoserine-G-sulfatase and B-galactosidase. Normal IQ shory, kyphoscolio, deaf and weak

Question 17

MPS 6 (Maroteux-Lamy)

Answer 17

Amylsulphatase B similar to hurler but with normal IQ

Question 18

MPS 7 (sly)

Answer 18

Beta glucoronidase variety of severity

Question 19

What are lipid storage diseases

Answer 19

Sphingolipids defects. Gauchers (glucocerebroside) Niemann Prak (sphingomyelin and cholesterol) Tay Sachs (GM2 gangliosidase)

Question 20

Chedrick Higashi

Answer 20

Microtubule defect. Defect in NK cells and platlets with autophagy of melanosomes leading to albinism

Question 21

Mucolipidases

Answer 21

Acummulation of glycoprotein and glycolipids. Primary (Sialidoses) Secondary (I-call disease) tertiary (Pseudohurler)

Question 22

I cell disease

Answer 22

Defect in NAcGluphosphotransferase leading to no M6P leading to inclusion bodies

Question 23

PseudoHurler Syndrom

Answer 23

Mild I cell, late onset, Survive to adult