Medical Power point..

1. Seminar on
CELL ORGANELLES
Dr.Simi M
Dept of Physiology
Sree Gokulam Medical College & Research Foundation.
26th August 2011.

2. Introduction
 Discrete organelles that subserve
distinct functions.
 Bounded by limiting membrane
“Membrane-enclosed organelles”
 Contain enzymes.

3. History
 Homogenised by disrupting cell
membrane with Tween 20
 Albert Claude (Nobel Prize 1974)
 Marker enzymes.

4. CELL ORGANELLES
 Nucleus
 Endoplasmic reticulum
 Golgi Apparatus
 Mitochondria
 Lysosomes
 Peroxisome
 Ribosome
 Centrosomes

5. CELL ORGANELLES

8. THE NUCLEUS – stores,replicates &
reads Cell’s Genetic Information.
 Described by Robert Brown (1831)
 First Discovered & Largest organelle
 2-20 µm in diameter

9. Structure of Nucleus
 Sorrounded by double membrane
- outer membrane
- inner membrane
 Space b/w 2 membranes
"Perinuclear Cistern"

10. Structure of Nucleus

11. Structure of Nucleus

12. Structure of Nucleus

13. THE NUCLEUS
Nuclear Pores
“Nuclear Localisation Sequence”
Nuclear Pore Complex
Outer diameter : ~100 nm
Resting State : ~9 nm

15. Nucleus : Storehouse of DNA
 Chromosomal DNA present inside
nucleus
 Chromatin
- Heterochromatin
- Euchromatin
 Transport pathways
-Importins
-Exportins

17. Nucleolus
 described by Gabriel Valentin 1836
 prominent in cells actively
synthesizing proteins
 Function :
- RNA Processing
- Ribosome synthesis

18. ENDOPLASMIC RETICULUM
 Web of Tubules or Saccules
sorrounding the nucleus.
 “ Railway Track Appearance ” - EM
George Palade
(Nobel Prize 1974)
 2 forms : RER & SER

19. RER SER
Granular  Agranular
Ribosome studded Not Ribosome
studded
PROTEIN SYN LIPID &STERIOD SYN
Egs:
Egs: Leydig cells
Nissl Granules Cells of Adrenal
Russel bodies Cortex
Acinar cells

20. Structure of Endoplasmic Reticulum

21. ENDOPLASMIC RETICULUM
 Functions:
1.Synthesis of proteins,Glycoprotein &
Lipoproteins
2.Detoxification of various drugs
3.Major Reservoir of Ca2+ ions
Modified ER (Sarcoplasmic Reticulum)

22. Microsomes :
Formed by automatic reassembly of
disrupted complex ER on cell
fractionation.
Func:
1.Valuable tool for understanding
metabolism of compounds.
2.Study drug – drug interactions

23. MITOCHONDRIA - Site of
Oxidative Energy Production.
 “Power House of the Cell”
 Richard Altman (1886)
 Carl Benda coined the term
 0.5 – 1 µm in diameter &
 7 µm in length.

24. Structure of Mitochondria
 Described as a “Balloon with in a
balloon”
 Cigar shaped organelles/
Sausage shaped organelles
 2 membrane
- outer membrane
- inner membrane (Cristae)
Lollipop shaped globular structures

25.  Define 2 distinct internal compartments
- inter membrane space
- matrix space
 Capable of “Self replication”
 Short Life span

26. Structure of Mitochondria

30. Mitochondrial Enzymes
 A. Membrane enzymes
1.Enzymes of outer membrane
a) Cytochrome b5 & b5 reductase
b) Fatty acid coA synthase
c) Phospholipase A
d) Nucleoside diphosphokinase

31. Mitochondrial Enzymes
 2. Enzymes of inner membrane
a) Cytochrome b,C1,C,a& a3
b) NADPH dehydrogenase
c) Succinate dehydrogenase
d) Electron transferring flavoproteins
e) β-OH-butyrate dehydrogenase
f) Carnitine – palmitoyl transferase
g)All translocases

32. Mitochondrial Enzymes
 B. Enzymes of inter membrane space
a) Adenylate kinase
b) Nucleoside diphoshokinase
c)Sulfite oxidase

33. Mitochondrial Enzymes
 C. Enzymes in the matrix
a) Pyruvate dehydrogenase complex
b) Citrate synthase
c) Isocitrate dehydrogenase
d)Malate dehydrogenase
e) Fatty acid oxidation system
f) Ornithine transcarbamoylase
g) α-oxoglutarate dehydrogenase
h) Aconitase

35. MITOCHONDRIA
 Functions:
 Critical manufacturer of ATP.
 Programmed Cell death (Apoptosis)
intracellular Ca 2+ stores.

36.  ETC (innermemb )
 TCA Cycle (matrix )
 β-Oxidation of FA (matrix )
 Ketone body production
 Urea,Heme,Pyramidine syn
 Gluconeogenesis

37. Mitochondrial diseases dt mtdna
mutations
 Leber hereditary optic neuropathy (LHON)
 NARP, Leigh's disease
 MELAS
 MERRF
 Progressive sensorineural deafness
 Chronic progressive external
ophthalmoplegia (PEO)
 Pearson syndrome
 Kearn-Sayre syndrome (KSS)

39. GOLGI APPARATUS – stack of
pancakes/stack of dinner plates
 Also called “Dyctyosome”
 Collection of membrane enclosed sac
(abt 6 sacs )
 Camillo Golgi (Nobel Prize 1906)
 Continuous with ER
 >200 enzymes
 Processing station

40. Structure of Golgi Apparatus

41.  Polarised structure with cis & trans
sides
 Membrane vesicle containing proteins
bud off from ER
↓
 fuse with the cistern on the cis side of
the apparatus.
↓
 passed via other vesicles to the middle
cisterns
↓
finally to the cistern on the trans side,
from which vesicles branch off into the

44. Functions :
 Site for Packaging of proteins
synthesized in ER into vesicles
 Formation of Lysosomal enzymes
 Transport to other organelles
 Glycosylation of proteins

45. LYSOSOMES – Cell’s Trash Incinerato
 Discovered by Rene de Duve (Nobel Prize
1974)
 Large irregular structures bounded by
membrane
 Lysosomes act as “cellular stomachs,”
breaking down bacteria
and the debris from
dead cells that have
been engulfed by a cell.

46. LYSOSOMES
 Proton Pump or H+-ATP ase
acidic interior (ph 5.0)
 40 types of enz
“Acid Hydrolases”
 Specially adapted lys.membrane
Clinical app: Gout(loss of memb
integrity)
 Endocytic Vesicle
 Autophagy : “Multivesicular body”

47. LYSOSOMES
 Particularly abundant in cells involved
in phagocytic activity. (Eg: Neutrophils &
Macrophages)
 3 Forms of lysosomes
Primary
Secondary
Residual Bodies

48. Important Lysosomal Enzymes
Proteolytic 1.Cathepsins 2.Collagenas 3.Elastases
Enzymes es
Lipolytic 1.Lipases 2.Phospholip 3.Fatty acyl
Enzymes ase Esterases
Carbohydrat 1.α- 2. β- 3.Hyaluronid 4.Aryl
e splitting glycosidase galactosidas ase Sulphatase
enzymes e
Nucleic acid 1.Ribonuclea 2.Deoxy
Hydrolysing e Ribonucleas
enzymes e
Other 1.Acid 2.Catalase
enzymes Phosphatse

49. Lysosomal storage diseases
- Congenital absence of Lysosomal
enzymes

50. Disease Enzyme Unique Features
deficiency
Fabry disease α-galactosidase A Cutaneous
Angiokeratomas&
hypohydrosis
Gaucher disease Acid β glucosidase HSM & Skeletal Dysplasia
Niemann - Pick Sphingomyelinase MR,Seizures & Lung
Failure
disease
Tay- Sachs disease β-hexaminidase A MR,Macrocephaly &
Hypercuisis in infants
Hurler disease α-L-iduronidase MR,Coarse facies,CVS inv
Pompe disease Acid α-glucosidase Myocardiopathy

51. Functions of Lysosomes:
 1.Contain enzymes essential for
intracellular digestion
2.Kill & remove foreign bodies
3.Acrosome :- specialised lysosome
4.Autolysis
5.remove IC pdts of metabolism

52. Ribosomes – Sites of Protein
Synthesis.
 Granular structures present on surface
of ER & also as free
 1st observed by George Palade (1953)
 Non membrane bound organelle
 Measure ~ 22 x 32 nm.
 Contain 85% RNA of cell

53. Ribosomes
 Each is made up of a large and a small
subunit
 on the basis of their rates of
sedimentation in the ultracentrifuge, the
60S and 40S subunits
 Polyribosomes(3-5)
 Func
Main Site of Protein Synthesis

54. PEROXISOMES
 also known as microbodies
 “Subcellular respiratory organelles”
 0.5 µm in diameter
 Predominantly present in Hepatocytes &
Tubular Epithelial cells.
 surrounded by a membrane.

55.  This membrane contains a no of
peroxisome-specific proteins
 PEROXINS-
the protein Chaperones,various proteins
with specifc signal sequence are directed
to peroxisome.

56. Function:
 Essentially contain two types of Enzymes
:
 Oxidases : which are active in oxidation
of lipid
 Catalase : which act on Hydrogen
Peroxide to liberate Oxygen.

57.  Several years ago, a number of synthetic
compounds were found to cause
proliferation of peroxisomes by acting
on receptors in the nuclei of cells.
 These receptors Peroxisome
Proliferation Activated Receptors
(PPARs)

58. Peroxisome Proliferation
Activated Receptors (PPARs)
• Three PPAR receptors α ,β and γ have been
characterized.
• When activated, they bind to DNA,
producing changes in the production of
mRNAs.
• Mutations of the peroxisome
proliferators' activator receptor γ
(PPARγ) cause insulin resistance

59. Lysosomes Peroxisomes
Larger  Smaller
Formed from Golgi Formed by self-
Apparatus replication or budding
from smooth ER
Digestive organ of cell Detoxifying organ of the
cell
Contain Hydrolases Contain oxidases and
form H2O2
Helps in intracellular Along with
digestion of food, catalase,helps in the
bacteria,damaged cell detoxification of injurious
structures etc substances

60. Applied Physiology
 Perioxisomes protect from oxidative
stress (OS)
 1. Zellweger Syndrome
- peroxisome abnormal or absent
 2. Infantile Refsums Disease
- few proteins are affected
 3.Brown Schilders Disease
-insufficient oxidn of VLCFA by perox

61. Centrosomes –
 Situated near the nucleus
 made up of 2 centrioles
 surrounding amorphous pericentriolar
material.
 centrioles are short cylinders,
arranged at right angles
to each other.

62. Centrosomes –
 Microtubules in groups of 3 ,run
longitudinally in the walls of each
centriole.
 9 of these triplets
are spaced at regular intervals
around the circumference.

64. Centrosomes –
 “microtubule-organizing
centers” (MTOCs) that contain γ-
tubulin.
 Func:
monitor steps in cell division.
regulate chromosome movement

65. References
 1.Walter.F.Boron & Emile .L.Boulpaep
Medical Physiology 2nd edition
 2.Ganong’s Review of Physiology 23
rd
edition
 3.GK Pal Textbook of Medical Physiology
2nd edition
 4.Guyton & Hall Text book of Physiology
12th edition
 5.Vanders Human Physiology 8
th edition

66. References
 6.Sreekumari & Vasudevan Textbook of
Biochemistry 6th edition
 7.Harrison’s Principles of Internal
Medicine 17th edition
 8.Indu Khurana Textbook of Medical
physiology
 9.N Geetha Textbook of Medical Physiology
2nd edition.
 10.A.K Jain Textbook of Physiology
4th edition.

67. RECENT ADVANCES
 Organellar dysfunction in the pathogenesis of
pancreatitis.
 Acute pancreatitis is an inflammatory
disease of exocrine pancreas that carries
considerable morbidity and mortality; its
pathophysiology remains poorly
understood.
 Recent findings obtained on experimental
models, which reveal disordering of key cellular
organelles, namely, mitochondria,
autophagosomes, and lysosomes, in pancreatitis.
 Ref

68. RECENT ADVANCES
 (PPAR) represented by 3 types: PPAR alpha, PPAR
beta, PPAR gamma.
 PPAR alpha is a key regulator of fatty acid beta-
oxidation, participates in development of
inflammatory reaction and atherosclerosis
formation.
 PPAR gamma plays important role in lipid
metabolism, processes of cell differentiation
and growth, participates in glucose utilization
and mechanisms of insulin resistance. Specific
activators of PPAR gamma are glytazones
 Ref :http://www.ncbi.nlm.nih.gov/pubmed/14671562

69. RECENT ADVANCES
 The nuclear (PPAR gamma) in DM,HTN,atherosclerosis
 is a transcription factor that is activated by
polyunsaturated fatty acids and their
metabolites and is essential for fat cell
formation.
 PPAR gamma activators such as the glitazone
drugs lower glucose and lipid levels in patients
with type 2 diabetes and also have
antiatherosclerotic and antihypertensive effects.
 Ref :http://www.ncbi.nlm.nih.gov/pubmed/11395411.

70. Thank You !!!