Enzymatic Constituents of Cell Organelles - 1 Lecture NO: 1 st MBBS

1. Enzymatic Constituents of Cell Organelles - 1 Lecture NO: 1st MBBS Dr. Muhammad Ramzan

2. Cell Organelles – the definition • Organelle - Little organ- analogous to an organ • Are the specialized components of the living cell • Carry out various functions that are essential for cell life and metabolism • www.biology- online.org

3. Cell organelle – the backgroundAre insulated by membrane • All the organelle are Bilayered. Peroxisome is single layered • Ribosome has no membrane • Are always present and able to self replicate • Ribosome is produced by the Nucleolus • Their numbers , size and shape is variable • Are abundant in metabolically active cells like thyroid/ Pancreas • www.wikepedia.com – www.Khan academy.com

4. Cell Organelles - the list of 8 • Nucleus, Endoplasmic Reticulum and Golgi complex • Lysosome, Mitochondria and : • Ribosome • Peroxisome/ Micro bodies and • Secretary Vesicles • www.wikepedia. com

5. Cell organelle – Nucleus to secretary vesicles

6. Lysosomes – the definition Present in all cells except RBC • Are spherical vesicles which contain acid Hydrolases (50) to degrade all types of biological polymers • (Proteins; nucleic acids, CHO and lipids) • Lysosomes are referred to as Suicide bags because of their role in Autolysis • www.biology- online org. www.wikipedia.com

7. Lysosomes- the background • Lysosomal enzymes are synthesized in ERand pinched off from Golgi as Transport vesicles • Acid Hydrolases work best at acidic pH(5) VS pH 7.2 • Lysosome actively concentrate proton(H+) via Protonpump in its membranes via ATP hydrolysis • Degrade extra cellar material and damage organelle • www.biology – online.org – www.NCBI book shelf.org

8. Lysosome

9. Proton pump - Conc. H+

10. Role of Lysosomal MembranesPrevention of Damage • Lysosomal membranes prevent the leakage of the acid hydrolytic enzymes into Cytosole 1 • Their damage causes release of acid hydrolases which are inactive at neutral Cytosolic pH 7.2 2 • This provides double protection against the digestion of Cytoplasmic contents in membrane rupture

11. Synthesis of Lysosome • 2 pathways • Secretary pathway • Secretary endocytic pathway • Secretary pathway: Lysosome and their enzymes are produced separately and pinched off from Golgi • Enzymes in Transport vesicles and Lysosome bind together cytoplasm to have mature Lysosome

12. Synthesis of LysosomeEndocytic/secretary Pathway ```` • Extra cellular moles are taken up in the cell as endocytic vesicles which fuse with the early endosome • Early endosome matures into late endosome • Transport vesicles from Golgi fuse with lateendosome that also contain certain moles taken up by the Endocytosis • Enzymes in Transport vesicles are delivered to endosome via receptors of Mannose – 6 Phosphate • Transport vesicles and endosome are transformed into Lysosome

13. Endocytosis and Lysosome formation

14. Lysosome – the waste boxes • Constitute an Intracellular Digestive System for the : • Damaged cellular structures / debris • The materials taken by Endocytosis and Phagocytosis EXT • Food particles ingested by the cell • Unwanted Matter like Bacteria • Macromolecules like Proteins; nucleic acids, CHO and lipids

16. Lysosomal enzymes- Disposal of products • Lysosomes are now known to contain ˃ 50 acid Hydrolases that can digest all macro moles in the cells • The breakdown products are transported back to the Cytosole by specific transport proteins in the Lysosomal membrane • Functional deficiencies of these enzymes result in the Lysosomal storage disease like Gauchors" disease

17. Lysosomal enzymes – the list • Proteases : that degrade Proteins/peptides into AAs • Nucleases: Degrade DNA/RNA into mononucleotides • Phosphatases: Remove PO4 group from mononucleotides/Phospholipids • Lipases degrade lipids into fatty acids and glycerol

18. Lysosomal Storage diseasesGauchors" disease • The mutations of the genes for Lysosomal enzymes give rise to 30 different genetic diseases • Lysosomal storage diseases • There is accumulation of un degraded materials due to the deficiency of Lysosomal enzymes • Guachars" Disease: is due to the deficiency of the enzyme for the degradation of Glycolipids

19. Peroxisome – Produces H2O2is single layered • Peroxisome are so called as they all produce H2O2 through the process of per oxidation • Peroxisome are produced through self replication or from endoplasmic reticulum (ER) • Is a single layered organelle and is self replicated • Are present in all animal cells except RBC

20. Peroxisome – Oxidases and Catalasesthe major enzymes • Contain about 50 enzymes – Oxidases and Catalases • Oxidases splitorganic moles (FA) to produce H2O2 by the process of oxidation – A free radical • Catalases then split H2O2to water and O2 to make it safe • Peroxisome also break down uric acid and amino acids

22. Mitochondria – the cellular power house • Mitochondria, are power house of cells and the principal site for ATP production in aerobic cells • Extract energy from the nutrients to carry out cell function. • No. of mitochondria are variable and depend upon activity of the cell - from100 to several thousands like : • Thyroid gland, Pancreas and renal tubules

23. Mitochondria - structure in generalare mobile • Mitochondria are variable in size and shape • May be Globular or elongated • Mitochondria move freely with in the cells • Mitochondria are bilayered with Inner and Outer membranes.1 • An inter membranous space exists B/w the 2 layers 2

24. Mitochondria – structure

25. Composition of the Mito.membranes • Outer membrane of mitochondria is composed of about half lipids and half protein • Low Protein in the outer membrane render it permeable to molecules having molecular weight < 10,000KD • The inner one has 80% proteins and 2o% lipids and is less permeable to large molecules like LCFAs • This is significant for entry of FAs into matrix for oxidation

26. Mitochondria – Enzymes of membranes and matrix • Inner membrane has folding shelves and Cristie to ↑ the surface area forenzyme action • Cavity under inner membrane has fluid – the Matrix • Matrixcontains abundantly dissolved Oxidative enzymes to extract energy from nutrients • Liberated energyis utilized to synthesize ATP

27. Enzymes of outer Mitochondria membrane NO:2 • External surface of Outer mitochondrial membrane has • Fatty Acyl Co A Synthetase for the: • Activation of Long chain saturated fatty acid (LCSFA) • Inner surface of outer mitochondrial membrane has : • Carnitine Acyltransferase(CAT 1) to transfer LCSFA to the mitochondrial matrix

28. Enzymes of inner Mitochondrial membrane No:2+5 • Inner surface of external Mitochondrial membrane has : • Carnitine Acyltransferase 11 • It separates Carnitine from Acyl Carnitine so that LCSFA remains in the matrix for oxidation • Carnitine is translocated to the inter membranous space for reuse by the Carnitine Translocase

29. Enzymes of inner Mitochondrial membrane cont. and Matrix • Inner surface of the Inner Mitochondrial membrane has 5 enzymes including ATP Synthase and: • enzymes for Oxidative Phospho rylation (ETC) • Ribosome and Ribosomal DNA for protein synthesis • Matrix has the enzymes for : • Citric acid cycle and Fatty acid oxidation

30. Carnitine shuttle

31. Mitochondria – the synthetic role • Mitochondria have their own DNA with 37 no of genes that encode for the required Mitochondrial proteins • Have their Ribosomes and DNA on the : • inner Mitochondrial Membrane • Expression of these genes leads to the translation and synthesis of proteins via mRNA in the matrix • The product proteins are used with in the mitochondria

32. Mitochondria – the Metabolic role • Mitochondria carry out oxidation of the nutrients in matrix like FAs to yield energy for ATP synthesis • The process is called oxidation of FAs that releases 129no of ATP for a single mole of Palmatic acid(16C) • This energy is used to carry out cell function and survival

33. Electron transport chainOxidative Phosphorylation