Lysosomes Are Found in All Animal Cells
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8/3/2019 Lysosomes Are Found in All Animal Cells
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• Lysosomes are found in all animal cells, but are mostnumerous in disease-fighting cells, such as white bloodcells.
• This is because white blood cells must digest morematerial than most other types of cells in their quest tobattle bacteria, viruses, ana other foreign intruders.Several human diseases are caused by lysosome enzymedisorders that interfere with cellular digestion.
• Tay-Sachs disease, for example, is caused by a geneticdelect that prevents the formation of an essential enzymethat breaks down complex lipids called gangliosides.
• An accumulation of these lipids damages the nervoussystem, causes mental retardation, ana death in early cnildhood.
• Also, arthritis inflammation and pain are related to theescape of lysosome enzymes.
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Occurence
• Lysosomes are found in most of the animal cells and fewplant eells.The hepatic cell, pancreatic cells, kidney cells,etc. posses large number of lysosomes. According toMatile (1969) the lyososome in plant cell are membranebound. Generally lysosome are absent in the prokaryoticcells. Slime molds also have lysosome.
• Lysosome are pleomorphic as seen in the meristematiccells of root. The diameter may be 0 .4U to o .8u ;but inmammalian kidney cell lysosomes as long as 5 u havebeen found.
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Formation of Lvsosomes
The hydrolytic enzymes are formed in the RER.
• Enzymes have a terminal mannose-6-phosphate groupas a marker to be packaged in lysosomes.
• They are packaged at the trans face of the Gogi complex(termed the Trans Golgi Network -TGN).
• The newly formed vesicles that bud off are termed early endosomes or primary lysosomes. They are small and
have homogeneous, electron-dense contents.
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re
S Lysosome are saccate structure filled with digestiveenzyme. Each lysosome has two parts, vizjimitingmembrane and inner dence mass.
i)Limitting membrane:Sit is not double bound membraned like in other
organelles. It is single and composed of lipoproteins. The membrane however is bilayered like any unitmembrane.
u325S£ ,i*
PROTEINS/ENZYMES
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2)Inner dence mass:• f i t is the core of lysosome; it mostly enzymatic.The
membrane is impermeable to substrate the enzyme of which are present in the lysosome.
S Ocassionaly certain substance called labilizers detabilizethe membrane causing the enzyme to come out.
Alternatively, there are substance called stabilizer whichstabilize the membrene.^The limited permeability of the mambrane prevent
excessive digestion of cellular component by the lyticenzyme of lysosome.
v"The enzyme present in the lysosomeare-Nuclease,Phosphatase,Lipage,Glycosidase and
Sulphatases.
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> Lysosomes are polymorphic assuming various shapesdepending on the cell type and situation. Basicallly thereare two types of lysosome Viz,
1) primary lysosome
2) secondery lysosome
a) Phagosomesb) Residual bodiesc)Autohagic vacuoles
1) Primary lysosome
There are sac like stucture produce like directly froER from the golgi bodies.
2) secondery lysosome
a) Phagosomes:These are also known asheterophagosomes or digestive vacuoles. When a foreign
gene enters the cytoplasm, the plasma membrane formsasac around these substance. These are around these
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substances. These are the phagosome or pinosomes.Thelytic enzyme present in phagosome digest the foreignsubstance. The phenomenone is called Phagocytosis orpinocytosis.
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b) Residual bodies :After the digested meterial haspas out of the lysosome, the undigested material remainswithin the lysosome. Such lysosome with residualsubstrate are called residualbodies.lt may remain withinthe cell or very often they are pushed out of the cell by exocytosis.
c)Autophagic vacuoles :Ocassionally, a lysosomemay digest a part of the cell(ER,mitochondria).This is amechanism to digest the a part of cell without destroyingthe entire cell.Iiver cells show autophagic vacuoles orautophagosome under starvation.
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Origin of lysosome
a)Extra cellular origin : Vacuoles absorbed due topinocytosis or phagocytosis may become secondery lysosome after fusing with primary lysosome.
b)Origin from golgi bodies: There are enough evidence tothat lysosome are produce from golgi bodies at the heightof their secretory activity.
c)Origin from ER : Acorrding to Novikoff (1965), the roghER gives rise to the lysosome.
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COURSE NO: GP 508 (2+1)
CELL BIOLOGY AND MOLECULAR
GENETICS
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three special properties
i)The Proton pump 2 )Gtyco protein
coat ̂ Transporter channel
i) The proton pump:
S It an ATP driven proton [H +] pump to maintain a low pH(4 .5-5.5) in the lysosomal compartment.
Has a lollipop' structure similar to the F 1 and F° of mitochondria, and consisting of.
S A head containing 6 polypeptide units.
s A stalk contains 5 polypeptide units.S It is inhibited by n-ethylmaleimide.
2) A glycoprotein coat:
V rich in carbohydrates, on its inner surface to protect itagainst hydrolysis by its own enzymes
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S by facilitated diffusion; S by active transport;S by co-transport using the proton (H+) gradient to provide
the energy for transport.S They early endosomes (primary lysosomes) may fuse with
phagocytic or other vesicle to form late endosomes orsecondary lysosomes.
• Transporter channels that transport break -downproducts such as amino acids, glucose, nucleotides andother small molecules out of the lysosome. Thesemolecules may move out,
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Major function oflysosome:
• The main function of lysosome is digestion of intracelluler substances.
• Acorrding to Hirsch and Coh (1964), lysosome help indestyoing the dead cell from tissue.
• Recently it has been found out that in some animals(frog), lysosome play an important role inmetamorphosis.
• Lysosome also perhaps help in the formation anddestruction of bone cells. They digest ingested materialand aged or damaged organelles
Functions of Lysosomes
Lysosomes may be involved infollowing pathways:
1. Phagocytosis2. Autophagocytosis
3. Formation of endosomes
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4. Receptor-mediated endocytosis
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osis:Phagocytosis is the process by which the cell engulfs particulate
matter (>o-5 m) from the extra cellular space, and digests it by lysosomalaction. Three main cell types are capable of performing this function.
a) Macrophages:• are widely distributed in the connective tissue around the body
•
phagocytose and digest all particulate matter in the extracellular space,including micro-organisms, foreign particles and damaged cells.• are derived from monocytes, circulating in the peripheral blood.• may have different names in different tissues such as Kupffer cells in the
liver, osteoclasts in bone, and microglia in the central nervous system.
b) Neutrophils: In the peripheral blood, which phagocytose and digestmicroorganisms.
c) Eosinophils: In the peripheral blood, which phagocytose and digestantigen-antibody complexes.
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Phagocytosis Binding
Adhesion of the particle tothe glycxjcalyx or specificreceptor on the plasmamembrane
. Extrusion of pseudopodia tosurround the particle. This
is mediated by actinfilaments.. Formation of a
phagocytic vacuolecontaining the engulfedparticle
- Fusion with a primarylysosome
Phagocytosis
Endocytoticvesicle
Secondarylysosome
Residual body
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2) Autophagocytosis:
• This is the process in which old or damaged organellesare broken down. It occurs in practically all cells as arecycling system. It is most marked in cells that are notreplaced, such as neurons.
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Autophagocytosisi. The organelle is surrounded
by vesicles, whichcoalesce-
2,. The coalesced vesicles
form a membranesurrounding theorganelle. This iscalled an autophagicvacuole. j
3. The autophagic vacuolefuses with one or moreprimary lysosomes toform seconlysosomes.
4. Residual bodies arelysosomes withpartially undigested material.
1 Organelle
Autophagicvacuole
Secondarylysosome
Residual body
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Dr. S.R.PatelAssociate Prof.;Dept. of botany;N.A.U,Navsari.
Movaliya Darshan j.First sem.M.sc(agrL) Dept. of Botany; N.M.CoUege of
Agriculture,Navsari
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osis and exocytosis
■ Endocytosis is the uptake of extra cellular fluid by
infolding of the plasma membrane, and formation of avesicle containing the extra cellular material. Thisprocess was formerly called pinocytosis.
■ Exocytosis is the reverse of pinocytosis, i.e. the extrusionof fluid contained in vesicles into the extra cellular space.
■ Endocytosis and exocytosis are important mostly formembrane flow. For example, exocytosis replaces theplasma membrane removed by phagocytosis. Similarly, exocytosis of secretion vesiclesmust be balanced by endocytosis.
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4) Receptor-mediated endocytosis:
• Receptor-mediated endocytosis is the process whereby cells that have a specific receptor take up specificmacromolecules.
• This process is used for the uptake of hormones, growthfactors, antibodies, lipoproteins etc.
• The receptors are integral membrane proteins.
• The molecule that binds to the receptor is termed theligand.
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Receptor-mediatedendocytosis
jl Binding of the ligand to the receptor.
-z- Lateral diffusion of the ligand-receptor complex.
3. Accumulation of clathrin, adaptor protein anddynamin on the cytoplasmic surface of the plasmamembrane at a particular site.
4. Formation of a pit, and accumulation of the ligandreceptor complex at the site of clathrinacculmulation.
'B- Deepening of the pit and formation of clathrin-coated vesicles containing theligand-receptor complex.
6. The vesicles lose their clathrin coat
7. The vesicles fuse with a primary lysosome (earlyendosome) and the ligand is cleaved from thereceptor.
8. Familial hypercholesterolaemia: is a condition inwhich there is defective binding of low densitylipoprotein (LDL) to its receptor.Receptor-mediated endocytosis of the LDL doesnot occur, and it accumulates as high levels in theblood.
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• Peroxisome are found in animal cell and also in the leaves
of higher plant.• These particles participate in the oxidation of substrateresulting in the formation of hydrogen peroxide.
• In plants, peroxisome are involved in photorespiration.• Structurally peroxisome are variable in shape and size
but are gnerally circular. They have an envalope of a single membrane made up of
protein and lipids enclosing a granular metxix.• In certain instances, the metrix is crystaline or
amorphous. The peroxisome catalize the H 20 2 production.
• In plants, the peroxisomes contain enzymes of glycolatepatheway.
P EROXISOMES AS SEEN IN AHUMAN LIVER SECTION
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History of Peroxisomes
* First observed by electron microscopy in animal cells (1950s), then in plantcells (1960s).
* Christian deDuve (1965)
©Isolated from liver cells by centrifugation9 Called them peroxisomes because they
generate and destroy H 2Oz
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Thel 5e7oxisome
Single membraneV Roughly spherical
* 0.2 - 1.7JU11
V Composition varies
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Number and Size of Peroxisomes VaryDepending on Environment
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Preperoxisomaltemplate
Subset 1 ofmembrane proteins
Nascentperoxisomes
m
e
B
i
o
g
e
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i
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Ea
rly peroxisomal prec
Subset 2 ot membraneproteins _____ 1 ________
Subset 2' ofmembrane proteins _____ 1 ________
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ursors
Prepe^ox somalendo^eribraneSubset 1 of
memb'aneproteins __ I ____ Subset 2 olmembraneproteins
__ 1 ____
Nature Reviews | Molecular Cell Biolo
gy
Metabolic Functions
of̂ *^ PeroxisomesYeasts® Biosynthesis: lysine@Dearadat ion: amino acids, methanol, p-oxidation of fattyacids, decomposition of hydrogen peroxide, glyoxylate cycle.
I arly peroxisomalprecursor
Nascentperoxisome
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Fungi@> Bi osy nth esi s: penicillin©Degradat ion: p -oxidation of fatty acids, decomposition ofhydrogen peroxide, glyoxylate cycle.
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Microbodies
Lysosomes
Peroxisome
Glyoxisome
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@ Degradation: purines, some reactions of photorespiration (theconversion of glycolate to glycine and of serine to glycerate),p-oxidation of fatty acids, decomposition of hydrogen peroxide,glyoxylate cycle.
Mammals@ Biosynthesis: ether phospholipids (plasma log ens), cholesterol
and bile acids, polyunsaturated fatty acids
@ Degradation: amino acids, purines, prostaglandin, polyamines,a-oxidation of fatty acids, p-oxidation of fatty acids, decompositionof hydrogen peroxide.
Humans@ Biosynthesis: ether phospholipids (plasma log ens), cholesterol
and bile acids, polyunsaturated fatty acids.@ Degradation: amino acids, purines, a-oxidation of fatty acids,
p-oxidation of fatty acids, decomposition of hydrogen peroxide.
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Peroxisome in Plants
9 P -oxidation of fatty acids
9 Glyoxylate cycle
9 Photorespiration (Glycolate pathway)
9 Degradation of purines
9 Decomposition of hydrogen peroxide
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Purine Degradation© Nucleic acid purine moieties (adenine and guanine)
are degraded to uric acid
o2 h 2o2 . . o ¥L,0 2 xanthine uric acid allantoin
Xanthine oxidase Urate oxidase
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• High urate oxidaseconcentrations contributeto formation of crystallineinclusions
• All purine degradationleads to uric acid
hypoxanthine xanthine xanthine xanthine uric acidoxidase oxidase
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X X
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Oxidases The oxidases use molecular oxygen to remove hydrogenatoms from specific organic substrates
A variety of compounds, including L-amino acids,D-amino acids, polyamines, methanol, urate,
xanthine, and very-long-chain fatty acids, serve assubstrates for the different oxidases
Peroxide Detoxification
9 Oxidases use 0 2 to oxidize organic substances andproduce hydrogen peroxide (H 20 2)
— e.g., H 20 2 generated by glycolate oxidasereaction, P-oxidation of fatty acids.
9 Peroxisomes also contain catalase, the enzyme thatdegrades H 20 2.
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Importance of H 202 degradation2H202 atdase 2II20+02
Peroxisomes contain a high concentration of catalase,a heme protein
H - - O - - O - - H
HO- -OH (?)
• Other reactive oxygen species (ROS) are formed inperoxisomes
Reactive Oxygen Speciesler le" le" le"
— m — H202 ̂—► OH -+ OH h* — p» H20
■ ■■ • a ■ ■■■■ B H m m m m
. 0 - 0 ' ' O ' O : H:0:0:H H:0:+ O^H H:0-HSuperoxide anion Hydrogen Hydroxyl radical
(radical) peroxide
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# Cause damage to lipids, proteins, DNA
4 Amount ROS is reduced by catalase, and superoxide dismutase(SOD) 20 2" ------------- - 0 2 + H 202
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Microbodies: The cells of plants, fungi, certain protozoa and liver cellsof vertebrates contain certain small granular structures
associated with ER, mitochondria and chloropasts. Thesespherical bodies ranging in size from o .2 \i to 1.5a have acentral cristalline core and are called microbodies.
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Peroxisoma zymesKv y
J | RU HI IOSC -I.S-hlsphnsphatf rariK>xvtas4 >/oxywna<i*' 2 \
PhosphoRlycolate phosplutasc 3 1 Clytolate oxidase
_4jGlulamntr:glyoxylrtir nmliMHniissroi .iv
S | <;1><-I IMT ttt^rtHHixylrtN.' .■:■ I serin* - hydmxyiiwlliyl
IransfonWi* 6 \ SrrtiH«:RlyoxylflU' amlnotransffcraM _7 J I lydroxypyruv.»U- rt-ducl.u*-SJClyccraip kinase 9j Caialase
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Glyoxisome
*Glyoxisome are found in the cells of yeast andcertain other fungi(Neurospora) and also seeds(oil reach) of many higher plant.
+They are similar to peroxisome except thattheire core consists of dence rods of 6.o|im indiameter.
* Functionally the glyoxisome contain enzymes for fatty acids mtabolisome, involved in the conversion of lipids tocarbohydrate during germination.
♦ The glyoxisome play an important role in the glyoxisomecycle.
♦ The enzyme Urate oxidase and allantoinase are alsofound in glyoxisomes.
+ Urate oxidase converts uric acids to allantonin,while
allantonase hydrates allantonin to allantonic acidduring the degrading of purines.
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Lysosomes
(Gr. Lyso=digestive, soma=body)
First discovered in 1949 as dence round bodies
,lysosomes were called pericanalicular bodies. It was de
Duve ,(i955) who gave the present name. They are
membrane bound organelles. They are contain hydrolytic
enzymes.They have acidic contents (pH 4.5- 5.5) and
electron-dense heterogeneous contents.
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• The discovery of lysosomes involved the use of acentrifuge to separate the various components of cells.
• In the mid-twentieth century, the Belgian scientistChristian Reni de Duve was investigating carbohydrate
metabolism of liver cells and observed that that the cellsreleased an enzyme called acid phosphatase in largeramounts when they received proportionally greaterdamage in the centrifuge.
• To explain this phenomenon, de Duve suggested that thedigestive enzyme was encased in some sort of membrane-bound organelle within the cell, which he
dubbed the lysosome.• After estimating the probable size of the lysosome, he wasable to identify the organelle in images produced with anelectron microscope.
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PlasmaMembran
LipidBilaye
FigureHydrolyti
c hnzyiMixture
nzvm
Glycosylated
Membrane Transport
Anatomy of the Lysosome
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Lysosomes are spherical organelles contained by a singlelayer membrane, though their size and shape varies to someextent.
• This membrane protects the rest of the cell from the harshdigestive enzymes contained in the lysosomes, which wouldotherwise cause significant damage.
• The cell is further safeguarded from exposure to the biochemicalcatalysts present in lysosomes by their dependency on an acidic
environment.• With an average pH of about 4.8, the lysosomal matrix is favorable
for enzymatic activity, but the neutral environment of the cytosolrenders most of the digestive enzymes inoperative, so even if alysosome is ruptured, the cell as a whole may remain uninjured.The acidity of the lysosome is maintained with the help of hydrogen ion pumps, and the organelle avoids self-digestion by