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ENDOPLASMIC RETICULUM Functions: 1.Synthesis of proteins,Glycoprotein & Lipoproteins 2.Detoxification of various drugs 3.Major Reservoir of Ca2+ ions Modified ER (Sarcoplasmic Reticulum)
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
MITOCHONDRIA - Site ofOxidative 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.
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
Define 2 distinct internal compartments - inter membrane space - matrix space Capable of “Self replication” Short Life span
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
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
Mitochondrial Enzymes B. Enzymes of inter membrane space a) Adenylate kinase b) Nucleoside diphoshokinase c)Sulfite oxidase
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
MITOCHONDRIA Functions: Critical manufacturer of ATP. Programmed Cell death (Apoptosis) intracellular Ca 2+ stores.
ETC (innermemb ) TCA Cycle (matrix ) β-Oxidation of FA (matrix ) Ketone body production Urea,Heme,Pyramidine syn Gluconeogenesis
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
Functions : Site for Packaging of proteins synthesized in ER into vesicles Formation of Lysosomal enzymes Transport to other organelles Glycosylation of proteins
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.
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”
LYSOSOMES Particularly abundant in cells involved in phagocytic activity. (Eg: Neutrophils & Macrophages) 3 Forms of lysosomes Primary Secondary Residual Bodies
Important Lysosomal EnzymesProteolytic 1.Cathepsins 2.Collagenas 3.ElastasesEnzymes esLipolytic 1.Lipases 2.Phospholip 3.Fatty acylEnzymes ase EsterasesCarbohydrat 1.α- 2. β- 3.Hyaluronid 4.Aryle splitting glycosidase galactosidas ase Sulphataseenzymes eNucleic acid 1.Ribonuclea 2.DeoxyHydrolysing e Ribonucleasenzymes eOther 1.Acid 2.Catalaseenzymes Phosphatse
Lysosomal storage diseases - Congenital absence of Lysosomalenzymes
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
Ribosomes – Sites of ProteinSynthesis. 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
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
PEROXISOMES also known as microbodies “Subcellular respiratory organelles” 0.5 µm in diameter Predominantly present in Hepatocytes & Tubular Epithelial cells. surrounded by a membrane.
This membrane contains a no of peroxisome-specific proteins PEROXINS- the protein Chaperones,various proteins with specifc signal sequence are directed to peroxisome.
Function: Essentially contain two types of Enzymes : Oxidases : which are active in oxidation of lipid Catalase : which act on Hydrogen Peroxide to liberate Oxygen.
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)
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
Lysosomes PeroxisomesLarger SmallerFormed from Golgi Formed by self-Apparatus replication or budding from smooth ERDigestive organ of cell Detoxifying organ of the cellContain Hydrolases Contain oxidases and form H2O2Helps in intracellular Along withdigestion of food, catalase,helps in thebacteria,damaged cell detoxification of injuriousstructures etc substances
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
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.
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.
Centrosomes – “microtubule-organizing centers” (MTOCs) that contain γ- tubulin. Func: monitor steps in cell division. regulate chromosome movement
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
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.
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
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
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.