The Endomembrane System

1. “Lysosome and Peroxisome” “Membrane Flow and Sorting” adalan \all about lysosomes\a tour inside the cell.FLV Mr. Blithe Endomembrane System:

2. Endomembrane System: History Today, scientists know that the endomembrane system includes the  ENDOPLASMIC RETICULUM (ER),  GOLGI APPARATUS , and  LYSOSOMES .  The first Endomemembrane System was discovered by Camillo Golgi in the late 1800s.

3. The endomembrane system is composed of the different inter-related membrane sacs within the cytoplasm of the cell.

4. The Endomembrane System functions in: Synthesis, Modification, Sorting and Transport. BIOMOLECULES

5. Introducing the LYSOSOMES

6. Plant cell Animal Cell

7. lysosomes "The police force of the cell" "suicide bags“ “The cells' garbage disposal system. It is the…

8. Structure… Lysosomes are spherical membranous bags that contain enzymes (Acid Hydrolases) . size varies from 0.1–1.2 μm . The lysosomal enzyemes are capable of digesting all varieties of biological molecules.

9. What Do Lysosomes Do? Functions: Digestion of worn out or non functional organelles. Metabolic functions Degradation of nonuseful tissue.

10. Continuation…What Do Lysosomes Do? These membrane-bound organelles contain a variety of enzymes called  hydrolases  that can digest proteins, nucleic acids, lipids, and complex sugars. Lysosomes break down all varieties of biological molecules into their constituent parts, which are then recycled.

11. Lysosomal Enzymes Biological Molecules Amylase Carbohydrates Proteases Proteins Nucleases Nucleic acids Lipase Lipids Phosphoric acid Monoesters Some important enzymes found within lysosomes include:

12. All those hydrolytic enzymes are produced in the endoplasmic reticulum, and to some extent in cytoplasm are transported and processed through the Golgi apparatus and through Golgi apparatus they pinch off as single membrane vesicles. adalan \endo_a.gif In addition, vesicles that bud off from the plasma membrane via  endocytosis  are also sent to lysosomes, where their contents — fluid and molecules from the extracellular environment — are processed. The process of endocytosis is an example of reverse vesicle trafficking, and it plays an important role in nutrition and immunity as well as membrane recycling.

13. Lysosomal enzymes works best in an acid pH approximately 5.

14. How do Lysosomes break down macromolecules and foreign substance inside the cell? the lysosome membrane fuses with the membrane of a food vacuole or Phagosome (particle containing vessel) and squirts the enzymes inside. adalan \all about lysosomes\lysosomes at work.FLV This action is called AUTOPHAGY… adalan \all about lysosomes\autophagy.avi - YouTube.FLV The digested food can then diffuse through the vacuole membrane and enter the cell to be used for energy or growth.

15. The Lysosomal Membrane Two Important Function: 1. maintain the organelles low pH level. 2. retains the dangerous acid Hydrolases while permitting the final products of digestion to escape so that they can be used by the cell or excreted. The only thing that keeps the cell itself from being digested is the membrane surrounding the lysosomes.

16. There's Dangers Ahead...! When the cell is injured or deprived of oxygen and when excessive amount of Vitamin A are present, the lysosomal membrane becomes fragile. Such ruptured results in Self-Digestion of the cell, a process is called AUTOLYSIS …

17. There's Dangers Ahead...( CONTINUATION) If the lysosomal enzymes do not reach the target it causes Lysosomal Storage Disease. . Pompe's disease an inherited disorder that is caused by the lack of the enzyme hydrolase acid alpha glucosidase (GAA) that is contained in lysosomes. GAA is responsible for breaking down glycogen to glucose. Inclusion cell disease (I-cell disease) this condition is caused by the failure to tag, by phosphorylation, all of the hydrolytic lysosomal enzymes with mannose-6-phosphate. This malfunction means that instead of the enzymes being transported to the lysosome, they are instead secreted from the cell.

18. THE PEROXISOMES.

19. Peroxisomes Peroxisomes were first discovered by Christian de Duve . History… Peroxisomes , also called microbodies, are membranous sacs containing powerful enxymes called PEROXIDASE. .

20. Peroxisome Biogenesis Peroxisomes biogenesis has been unclear. Recent experiments indicate that peroxisomes originate or bud off from the endoplasmic reticulum.

21. Structure… Peroxisomes are about the size of lysosomes (0.5–1.5 µm) and like them are bound by a single membrane. They also resemble lysosomes in being filled with enzymes. contains a p eroxisomal t argeting s ignal ( PTS ). contain about 50 different enzymes. have crystalline and non-crystalline inclusions .

22. Peroxisomes stand out in  electron micrographs Urate Oxidase crystalline core

23. Function… major sites of oxygen utilization Detoxify harmful or toxic substance like alcohol and formaldehyde. Disarm oxygen free radicals such as superoxide radical by converting them to hydrogen peroxide (H 2 O 2 ). And reduce Hydrogen peroxide to water and oxidizes organic compounds ( CH 2 ) 2H 2 O 2 2H 2 O+ O 2 H 2 O 2 + CH 2 2H 2 O+ C

24. Breakdown (by oxidation) of excess fatty acids. Breakdown of hydrogen peroxide (H2O2), a potentially dangerous product of fatty-acid oxidation. It is catalyzed by the enzyme catalase . Participates in the synthesis of cholesterol. One of the enzymes involved is reductase. Participates in the synthesis of bile acids. Participates in the synthesis of the lipids used to make myelin. Functions of the peroxisomes in the human liver:

25. There's Dangers Ahead...! Lack of peroxisomes or dysfunction may lead to: A mutation in peroxin 2 ( Pex2) , a peroxisomal membrane protein involved in import process, causes one form of Zellweger syndrome. It is a rare, congenital (present at birth) disorder characterized by the reduction or absence of peroxisomes (cell structures that rid the body of toxic substances) in the cells of the liver, kidneys, and brain. Zellweger syndrome is one of a group of genetic disorders called peroxisomal diseases that affect brain development and the growth of the myelin sheath, the fatty covering-which acts as an insulator-on nerve fibers in the brain

26. Adrenoleukodystrophy ( ALD) is a rare, inherited metabolic disorder that afflicts the young boy Lorenzo Odone , whose story is told in the 1993 film "Lorenzo's oil." In this disease, the fatty covering (myelin sheath) on nerve fibers in the brain is lost, and the adrenal gland degenerates, leading to progressive neurological disability and death.

27. Vesicular Transport transport vesicles play a central role in the traffic of molecules between different membrane-enclosed compartments. Vesicular transport is thus a major cellular activity, responsible for molecular traffic between a variety of specific membrane-enclosed compartments.

28. Coat Proteins and Vesicle Budding the formation of a vesicle by budding from the membrane. The cytoplasmic surfaces of transport vesicles are coated with proteins. Three kinds of coated vesicles clathrin-coated vesicles are responsible for the uptake of extracellular molecules from the  plasma membrane  by endocytosis as well as the transport of molecules from the trans Golgi network to lysosomes. 2. COPII-coated vesicles- bud from the ER and carry their cargo forward along the secretory pathway, to the Golgi apparatus. 3. COPI-coated vesicles bud from the ER-Golgi intermediate compartment or the Golgi apparatus and function in the retrieval pathways that serve to retain resident proteins in the Golgi and ER.

29. Clathrin (blue) A protein called coat protein II (COPII; green) A different protein called coat protein I (COPI; red)

30. How do the coated vesicles work? clathrin-coated vesicles are composed of two types of protein complexes clathrin and adaptor proteins. Clathrin plays a structural role by assembling into a basketlike lattice structure that distorts the membrane and drives vesicle budding. The binding of clathrin to membranes is mediated by a second class of proteins, called adaptor proteins. COPI- and COPII-coated vesicles composed of distinct protein complexes, which function analogously to  clathrin and adaptor  proteins  in vesicle budding

31. Vesicle Fusion The fusion of a transport vesicle with its target involves two types of events 1.the transport vesicle must specifically recognize the correct target membrane. 2. the vesicle and target membranes must fuse, thereby delivering the contents of the vesicle to the target organelle.

32. THE MEMBRANE TRANSPORT

33. Membrane Transport

34. Protein Synthesis

35. Pathway of Protein Synthesis Transcription

36. Targeting to the endoplasmic reticulum. Two groups of proteins are targeted to the ER: Proteins that are completely translocated into lumen of the ER. These  are soluble proteins destined for secretion, or for the lumen of another organelle. Proteins that are inserted into membranes, and hence are only partially translocated into the endoplasmic reticuluum . These proteins may be destined for ER, another organelle, or the plasma membrane. 

37. Protein Modification Lysosomal proteins from the rough endoplasmic reticulum (ER) must be further modified.

38. The Path Way Of Modifying Proteins… Modification of lysosomal proteins called hydrolases begins in the rough endoplasmic reticulum where a core oligosaccharide is added to the protein.

39. The hydrolases are then packaged into transport vesicles and transferred to the cis-cisterna of the Golgi apparatus. Inside the cis-cisterna of the Golgi, the core oligosaccharide is phosphorylated .

40. One of the mannose residues in the oligosaccharide receives a phosphate by way of two sequential reactions. The modification of the core oligosaccharide on the hydrolase enzyme results in the creation of an mannose 6-phosphate signal unique to proteins destined for the lysosome. Other signals target other proteins for different destinations.

41. Upon reaching the trans-Golgi, the M6P portion of the hydrolase binds to M6P receptors embedded in the trans-Golgi membrane. The membrane of the trans-Golgi then buds off into a vesicle containing the receptors and the bound hydrolases. AAA

42. Protein Sorting Aspects of protein sorting aaa

43. Protein Transport adalan \my report in cell bio\transport of protein from ER to its distination through golgi and sorting of protein.FLV

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