Lysosomes contain hydrolytic enzymes, the lysosomal acid hydrolases, which require an acidic pH(around 4. 8-5.0)to function. They include: Proteases Phospholipases Polysaccharidases Oligosaccharidases Glucosaminoglycan(GAG)-hydrolysing enzymes Lysosomal storage diseases are caused by defects of lysosomal enzymes resulting in intracellular accumulation of non-degraded substances. ysosomal storage diseases Mucopolysaccharidoses: I to VII Sphingolipidoses: Gaucher's disease, metachromatic leukodystrophy Neutral sphingolipidoses: Fabry disease, Niemann-Pick disease Neutral lipid-storage diseases: Wolman disease, cholesterol ester storage disease Peroxisomes(microbodies) Peroxisomes are round or oval membrane-bound organelles, with an average diameter of 0.5 um. They contain high concentrations of oxidative enzymes, i.e. catalase, D-amino oxidase and urate oxidase Peroxisomes are abundant in the liver and kidney Their functions include Synthesis of plasmalogens, important in cell membranes and myelin ile acid synthesis; Beta oxidation of fatty acids: the peroxisomal oxidation of ultra long-chain fatty acids is defective in X-linked adrenoleukodystrophy: Conversion of amino acids into glucose; The reduction of hydrogen peroxide, preventing tissue damage The prevention of excess synthesis of oxalate cytoskeleton The cytoskeleton is responsible for: Maintaining cell shape by mechanically strengthening it
Peroxisomes (microbodies) Peroxisomes are round or oval membrane-bound organelles, with an average diameter of 0.5 mm. They contain high concentrations of oxidative enzymes, i.e. catalase, D-amino oxidase and urate oxidase. Peroxisomes are abundant in the liver and kidneys. Their functions include: Synthesis of plasmalogens, important in cell membranes and myelin; Cholesterol synthesis; Bile acid synthesis; Beta oxidation of fatty acids: the peroxisomal oxidation of ultra long-chain fatty acids is defective in X-linked adrenoleukodystrophy; Conversion of amino acids into glucose; The reduction of hydrogen peroxide, preventing tissue damage; The prevention of excess synthesis of oxalate. Cytoskeleton The cytoskeleton is responsible for: * Maintaining cell shape by mechanically strengthening it; Lysosomes contain hydrolytic enzymes, the lysosomal acid hydrolases, which require an acidic pH (around 4.8–5.0) to function. They include: Proteases Lipases Phospholipases Nucleases Phosphatases Polysaccharidases Oligosaccharidases Glucosaminoglycan (GAG)-hydrolysing enzymes Lysosomal storage diseases are caused by defects of lysosomal enzymes resulting in intracellular accumulation of non-degraded substances. Lysosomal storage diseases Mucopolysaccharidoses: I to VII Glycoproteinoses Sphingolipidoses: Gaucher’s disease, metachromatic leukodystrophy Gangliosidoses Neutral sphingolipidoses: Fabry disease, Niemann-Pick disease Neutral lipid-storage diseases: Wolman disease, cholesterol ester storage disease Subcellular organelles 15
classification of peroxisomal disorders Peroxisomal structural defects, with generalised peroxisomal disorders Zellweger syndrome(cerebro-hepato-renal syndrome) Infantile Refsum disease x e enzyme deficiencies with an intact peroxisomal structure linked adrenoleukodystrophy Hyperoxaluria type Directional cell motility Intracellular movements, including organelle, protein and vesicle transport Providing the structural backbone of cilia and flagella, which produce beating movements on cell surfaces The structure of the axoneme in the flagellum of spermatozoa Spindle assembly and chromosome movement during mitosis Phagocytosis e Cell-cell and cell-extracellular matrix adherence Components of the cytoskeleton Microfilaments(8 nanometre diameter)containing polarised alpha-helical double-stranded polymers of actin. The two ends of the polymer are not Intermediate filaments(10 nanometre diameter), which are tissue-specific. Microtubules(25 nanometre diameter) containing tubulin monomers. The power for motility is provided by molecular motor proteins, the myosins (which move along actin microfilaments)and the dyneins and kinesins(which move along actin microfilaments and along microtubules). They are homolo- gous proteins, containing core structures of the P-loop NTPase superfamily which undergo change in conformation in response to nucleoside triphosphate binding and hydrolysis Functions of microfilaments Specific functions mediated by actin microfilaments include: Phagocytosis Linkage of transmembrane proteins to cytoplasmic proteins Amoeboid motility of macrophages and neutrophils
* Cell polarity; * Directional cell motility; * Intracellular movements, including organelle, protein and vesicle transport; * Providing the structural backbone of cilia and flagella, which produce beating movements on cell surfaces; * The structure of the axoneme in the flagellum of spermatozoa; * Spindle assembly and chromosome movement during mitosis; * Phagocytosis; * Cell–cell and cell–extracellular matrix adherence. Components of the cytoskeleton The cytoskeleton comprises: Microfilaments (8 nanometre diameter) containing polarised alpha-helical double-stranded polymers of actin. The two ends of the polymer are not equivalent. Intermediate filaments (10 nanometre diameter), which are tissue-specific. Microtubules (25 nanometre diameter) containing tubulin monomers. The power for motility is provided by molecular motor proteins, the myosins (which move along actin microfilaments) and the dyneins and kinesins (which move along actin microfilaments and along microtubules). They are homologous proteins, containing core structures of the P-loop NTPase superfamily which undergo change in conformation in response to nucleoside triphosphate binding and hydrolysis. Functions of microfilaments Specific functions mediated by actin microfilaments include: Phagocytosis; Linkage of transmembrane proteins to cytoplasmic proteins; Amoeboid motility of macrophages and neutrophils; Classification of peroxisomal disorders Peroxisomal structural defects, with generalised peroxisomal disorders Zellweger syndrome (cerebro-hepato-renal syndrome) Infantile Refsum disease Single enzyme deficiencies with an intact peroxisomal structure X-linked adrenoleukodystrophy Hyperoxaluria type 1 Cell physiology 16
The intermediate filament proteins include: Cytokeratin-epithelial cells Glial fibrillary acidic protein-glial cells Desmin -muscle cells Vimentin-mesenchymal cells Peripherin Neurofilament proteins: NF-L, NF-M, NF-H-nerve cells Interaction with myosin(thick) filaments in skeletal muscle fibres to allow skeletal muscle contraction: Anchoring of centrosomes at opposite poles of the cell during mitosis Contraction of intestinal microvilli Change in shape of activated platelets Outgrowth of dendrites and axons in developing neuroblasts The functions of the intermediate filaments include Anchoring of thick and thin filaments in skeletal muscle cells; Mechanical strengthening of axons Anchoring the nucleus in the cells, which is achieved by keratins Microtubule structure Thirteen lobular tubulin subunits form the walls of a hollow cylindrical or tubular structure. The tubular structure is stabilised by microtubule-associated proteins, including capping proteins There are two families of microtubule motor proteins, dyneins and kinesins They translocate along the microtubules in opposite directions. Microtubule based structures include cilia, axons and mitotic spindles Structure of cilia The core or axoneme of each cilium comprises two single central and nine peripheral pairs (doublets) of microtubules, composed of tubulins. This is referred to as a 9+2 array. Each peripheral microtubule pair possesses an inner and an outer cross-arm composed of dyneins. Each pair is connected by a series of radial spokes with the central pair, preventing buckling when the cilium bends. The dynein arms possess ATPase activity and an affinity for tubulin. The peripheral microtubule pairs are connected by interdoublet links
Interaction with myosin (thick) filaments in skeletal muscle fibres to allow skeletal muscle contraction; Anchoring of centrosomes at opposite poles of the cell during mitosis; Contraction of intestinal microvilli; Change in shape of activated platelets; Outgrowth of dendrites and axons in developing neuroblasts. The functions of the intermediate filaments include: Anchoring of thick and thin filaments in skeletal muscle cells; Mechanical strengthening of axons; Anchoring the nucleus in the cells, which is achieved by keratins. Microtubule structure Thirteen lobular tubulin subunits form the walls of a hollow cylindrical or tubular structure. The tubular structure is stabilised by microtubule-associated proteins, including capping proteins. There are two families of microtubule motor proteins, dyneins and kinesins. They translocate along the microtubules in opposite directions. Microtubulebased structures include cilia, axons and mitotic spindles. Structure of cilia The core or axoneme of each cilium comprises two single central and nine peripheral pairs (doublets) of microtubules, composed of tubulins. This is referred to as a 9 þ 2 array. Each peripheral microtubule pair possesses an inner and an outer cross-arm composed of dyneins. Each pair is connected by a series of radial spokes with the central pair, preventing buckling when the cilium bends. The dynein arms possess ATPase activity and an affinity for tubulin. The peripheral microtubule pairs are connected by interdoublet links. The intermediate filament proteins include: Cytokeratin – epithelial cells Glial fibrillary acidic protein – glial cells Desmin – muscle cells Vimentin – mesenchymal cells Peripherin Alpha-internexin Neurofilament proteins: NF-L, NF-M, NF-H – nerve cells Lamin Subcellular organelles 17
ciliary disorders Primary: primary ciliary dyskinesia is associated with abnormal ciliary activity, defec- tive or absent muco-ciliary transport and abnormal ciliary ultrastructure. Kartageners syndrome is associated with the triad of sinusitis, bronchiectasis and situs inversus Secondary(acquired) Toxins Environmental factors Microbial pathogens The immotile cilia syndrome is associated with lack of dynein cross-arms or ■ Cell polarity Epithelial cells demonstrate structural and functional polarity, with: An apical domain, which may bear cilia, microvilli, or stereocilia. This domain is the interface with the external environment A basolateral domain, which contains junctional complexes and cell adhesion molecules. This domain is the interface with the internal environment BIBLIOGRAPHY Danielli, J.F. Davson, H. A contribution to the theory of permeability of thin films. J. Cell mp. Physiol.,5(1935),495-508 Singer, S J& Nicolson, G. The fluid mosaic model of the structure of cell membranes science,175(1972),720-31 RECOMMENDED FURTHER READING Alberts, B, Johnson, A, Lewis, J, Raff, M, Roberts, K& Walter, P. Molecular Biology of The Cell, 4th ed. New York: Garland Science (Taylor Francis Group). 2003. Bolsover, S, Hyams, J, Shephard, E, White, H. Wiedemann, C Cell Biology. A Short Course. Hoboken, N]: John Wiley Sons, Inc. 2004 Hille, B. Jon Channels of Excitable Membranes. Sunderland, MA: Sinauer Ass 2001 Pollard, T D. Earnshaw, W. C. Cell Biology. Philadelphia: W.B. Saunders, 2002
The immotile cilia syndrome is associated with lack of dynein cross-arms or radial spokes. & Cell polarity Epithelial cells demonstrate structural and functional polarity, with: An apical domain, which may bear cilia, microvilli, or stereocilia. This domain is the interface with the external environment. A basolateral domain, which contains junctional complexes and cell adhesion molecules. This domain is the interface with the internal environment. BIBLIOGRAPHY Danielli, J. F. & Davson, H. A contribution to the theory of permeability of thin films. J. Cell. Comp. Physiol., 5 (1935), 495–508. Singer, S. J. & Nicolson, G. The fluid mosaic model of the structure of cell membranes Science, 175 (1972), 720–31. RECOMMENDED FURTHER READING Alberts, B., Johnson, A., Lewis, J., Raff, M., Roberts, K. & Walter, P. Molecular Biology of The Cell, 4th ed. New York: Garland Science (Taylor Francis Group). 2003. Bolsover, S., Hyams, J., Shephard, E., White, H. & Wiedemann, C. Cell Biology. A Short Course. Hoboken, NJ: John Wiley & Sons, Inc. 2004. Hille, B. Ion Channels of Excitable Membranes. Sunderland, MA: Sinauer Associates, Inc. 2001. Pollard, T. D. & Earnshaw, W. C. Cell Biology. Philadelphia: W. B. Saunders, 2002. Ciliary disorders Primary: primary ciliary dyskinesia is associated with abnormal ciliary activity, defective or absent muco-ciliary transport and abnormal ciliary ultrastructure. Kartagener’s syndrome is associated with the triad of sinusitis, bronchiectasis and situs inversus. Secondary(acquired): Drugs Toxins Environmental factors Microbial pathogens Cell physiology 18
Water and electrolyte balance Water balance In most steady state situations, water intake matches water losses through all sources. Water balance involves adjusting the effects of intake, which is deter- mined by thirst; renal dilution or concentration of urine; and losses, via the skin kidney, gastrointestinal tract, respiratory tract. The usual sources of water intake are ingested liquids, foods(fruits and vegetables) and endogenous metabolic water production Sensible losses: urine, stools and sweat. The ability to dilute and to concentrate Insensible losses: skin loss (insensible perspiration; exhaled air from the respiratory tract. Mechanisms of water homeostasis The mechanisms contributing to water balance can be outlined as Afferent mechanisms, involving hypothalamic osmoreceptors; non-osmotic arginine vasopressin sensors, activated by pain, stress, vomiting and extra lular fluid changes; and thirst sensors. Efferent mecha luding arginine vasopressin release, and increased thirst. osmolality and tonicity The total solute concentration(tonicity) of body fluids is maintained virtually constant Body fluid osmolality is defined by the ratio of total body solute to total body water. It is regulated at 280-95 mOsm/l Osmolality is a colligative property, depending on the number of dissolved solute particles, and not on size or structure of the particles. The maintenance of osmolality is achieved primarily through the regulation of water balance
Water and electrolyte balance & Water balance In most steady state situations, water intake matches water losses through all sources. Water balance involves adjusting the effects of intake, which is determined by thirst; renal dilution or concentration of urine; and losses, via the skin, kidney, gastrointestinal tract, respiratory tract. The usual sources of water intake are ingested liquids, foods (fruits and vegetables) and endogenous metabolic water production. The sources of water output comprise: Sensible losses: urine, stools and sweat. The ability to dilute and to concentrate urine allows for a wide flexibility in urine flow. Insensible losses: skin loss (insensible perspiration); exhaled air from the respiratory tract. Mechanisms of water homeostasis The mechanisms contributing to water balance can be outlined as: Afferent mechanisms, involving hypothalamic osmoreceptors; non-osmotic arginine vasopressin sensors, activated by pain, stress, vomiting and extracellular fluid changes; and thirst sensors. Efferent mechanisms, including arginine vasopressin release, and increased thirst. Osmolality and tonicity The total solute concentration (tonicity) of body fluids is maintained virtually constant. Body fluid osmolality is defined by the ratio of total body solute to total body water. It is regulated at 280–95 mOsm/l. Osmolality is a colligative property, depending on the number of dissolved solute particles, and not on size or structure of the particles. The maintenance of osmolality is achieved primarily through the regulation of water balance. 2 19