NUCLEUS The cell nucleus is a double membrane-bound organelle that contains the genetic information of the cell packaged

ged in the form of chromatin. The nucleus is considered to be one of the most important structures of eukaryotic cells as it serves the function of information storage, retrieval and duplication of genetic information. The key functions of the cell nucleus include deoxyribonucleic acid (DNA) replication, transcription and further post-transcriptional processing of pre-messenger ribonucleic acids (mRNAs), transport of the mature mRNAs into the cytoplasm where the translational events occur. Double membrane of nucleus is called the nuclear envelope, which consists of outer and inner nuclear membranes and perinuclear space between them. Nuclear pore complexes (NPCs) are large proteinaceous channels that perforate the nuclear membrane and allow transport of molecules into and out of the nucleus. In general, proteins destined for import contain nuclear localisation signal (NLS) and proteins destined for export contain nuclear export signal (NES). Small molecules (less than 5000daltons) diffuse fast, large proteins traverse the NPC much more slowly, proteins larger than 60 000daltons can barely enter by passive diffusion Genes are located in chromosomes inside the nucleus, which consists of a long DNA that is highly coiled and folded by proteins. A chromosome is confined to a distinct territory within the interphase nucleus. The genetic material, DNA is transcribed into pre-messenger RNA (pre-mRNAs) inside the nucleus. Further intron splicing of the pre-mRNA takes place. The mature mRNA is exported to the cytoplasm for translation. The clearest substructure in the nucleus in most eukaryotes is the nucleolus, which is the site of rDNA transcription and ribosome biosynthesis. The nucleolus is the nuclear subdomain that assembles ribosomal subunits in eukaryotic cells. The nucleolus disassembles at the beginning of mitosis, its components disperse in various parts of the cell and reassembly occurs during telophase. The nucleolus also contains proteins and RNAs that are not related to ribosome assembly and a number of new functions for the nucleolus have been identified. These include assembly of signal recognition particles, sensing cellular stress and transport of human immunodeficiency virus 1 (HIV-1) messenger RNA. The nuclear lamina is a meshwork of lamins that are a special class of intermediate filament proteins.The nuclear lamina gives shape and stability to the nuclear envelope .Together with the lamina the inner membrane proteins provide structural links between the DNA and the nuclear envelope. When a nucleus disassembles during mitosis, the nuclear lamina depolymerizes. Later in mitosis the nuclear envelope reassembles on the surface of chromosomes

MITOCHONDRIA: Mitochondria are double-membrane enclosed organelles; they specialize in ATP synthesis . They contain their own DNA, ribosomes and other components required for protein synthesis .
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There are two subcompartments in mitochondria: the internal matrix space and intermembrane space. The inner membrane encloses the matrix space and forms extensive invaginations called cristae. The outer membrane is in contact with the cytosol. New mitochondria are produced by the growth of preexisting organelles followed by fission Protein translocators mediate protein translocation across the mitochondrial membranes .The TOM complex transfers proteins across the outer membrane. The two TIM complexes (TIM 22, TIM 23) transfer proteins across the inner membrane. These complexes contain some components that act as receptors for mitochondrial precursor proteins, and other components that form the translocation channels.

PEROXISOMES: Peroxisomes are surrounded by only a single membrane, they dont contain DNA or ribosomes. They contain oxidative enzymes, such as catalase and urate oxidase Peroxisomes are major sites of oxygen utilization. Peroxisomes usually contain one or more enzymes that use molecular oxygen to remove hydrogen atoms from specific organic substrates in an oxidation reaction that produces hydrogen peroxide. Catalase uses hydrogen peroxydase to oxidase a variety of other substrates including phenols, phormic acid, formaldehyde and alcohol by the peroxidation reaction. This type of oxidation reaction is particularly important in liver and kidney cells, where peroxisomes detoxify various toxic molecules. When excess hydrogen peroxide accumulates in the cell, catalase converts it to water A major function of oxidation reactions performed in peroxisomes is the breakdown of fatty acid molecules. This process called oxidation shortens the alkyl chains of fatty acids sequentially in blocks of two carbon atom at a time, converting the fatty acids to Acetyl CoA. An essential biosynthetic function of peroxisomes is to catalyse the first reactions in the formation of plasmalogens, which are the most abundant class of phospholypids in myelin Thats why peroxisomal disorders lead to neurological disease. So the three major functions of peroxisomes are: detoxication, oxidation and formation of plasmalogens. The importance of the import process and of peroxisomes is demonstrated by the inherited human disease Zellweger Syndrome, in which a defect in importing proteins into peroxisomes leads to a profound peroxisomal deficiency. Individuals whose cells contain such empty peroxisomes have severe abnormalities in the brain, liver and kidnays and they die soon after birth. New peroxisomes are thought to arise from pre-existing ones by organelle growth and fission

ENDOPLAMSIC RETICULUM

All eucaryotic cells have an Endoplasmic Reticulum. The ER is organized into a netlike labyrinth of branching tubules and flattened sacs that are inteconnected . The ER membrane
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forms a continuous sheet enclosing a single internal space the ER lumen or the ER cysternal space. The ER has a central role in lipid and protein biosynthesis Functions of smooth endoplasmic reticulum (that lacks membrane-bound ribosomes) include: Lipid metabolism, synthesis of steroid hormones from cholesterol, synthesis of the lipid components of lipoprotein particles in hepatocytes, detoxification reactions in hepatocytes that are carried out by Cytochrome P450 family of enzymes. In muscle cells a special type of smooth endoplasmic reticulum sarcoplasmic reticulum sequesters calcium from the cytosol. The release and reuptake of calcium by the sarcoplasmic reticulum trigger the contraction and relaxation of muscles. The import of proteins into ER: The import of proteins into the ER begins before the polypeptide chain is completely synthesized that is import is a co-translational process. According to the signal hypothesis, ER signal sequence directs the secreted protein to the ER membrane and is then cleaved off by a signal peptidase in the ER membrane ER signal sequence is guided to the ER membrane by at least two componnets: A signal recognition particle (SRP) and SRP receptor in the ER membrane SRP is a complex particle consisting of six different polypeptide chains bound to a single small RNA molecule Once formed, the SRP-ribosome complex binds to the SRP receptor, which is an integral membrane protein exposed on the cytosolic surface of the RER This interaction brings the SRP-ribosome complex to membrane translocator The functions of ER: ER resident proteins contain an ER retention signal of four amino acids at their C-terminus that is responsible for retaining the protein in the ER ER resident proteins are protein disulfide isomerase (PDI), chaperone protein BiP that recognizes incorrectly folded proteins; calnexin and calreticulin that bind to incompletely folded protein and prevent them from undergoing irreversible aggregation The covalent addition of sugars to proteins is one of the major biosyntehtic functions of the ER. In protein glycosylation a precursor oligosaccharide is transferred to proteins in the ER The ER membrane synthesizes nearly all of the major classes of lipids The major lipid made is phosphatidylcholine, which can be formed in three steps from choline, two fatty acids and glycerol phosphate So we can summarize that the ER is the site of following processes: glycosylation of proteins formation of disulfide bonds, folding of proteins and assembly of protein subunits

THE GOLGI COMPLEX The Golgi apparatus consists of a collection of flattened, membrane-enclosed compartments, called cisternae. Tubular connections between corresponding cisternae link many stacks,
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thus forming a single complex, which is usually located near the cell nucleus and close to the centrosome. Each Golgi stack has two distinct faces: a cis face (or entry face) and a trans face (or exit face) . The Golgi complex consists of following parts: the cis Golgi network (CGN), cis cisterna, medial cisterna, trans cisterna and trans Golgi network (TGN) Proteins and lipids enter the cis Golgi network and exit from the trans Golgi network . Proteins exiting from the TGN move onward and are sorted according to their next destination: lysosomes, secretory vesicles or the cell surface

The function of Golgi complex: Glycosylation of lipids and proteins Assembly and glycosylation of proteoglycans, that are important components of extracellular matrix Addition of Mannose-6-Phosphate (M6P) to lysosomal hydrolases Sorting and packaging of molecules for further transport to lysosomes, plasma membrane or secretory vesicles

LYSOSOMES: Lysosomes are membrane-enclosed compartments filled with soluble hydrolytic enzymes . Lysosomes contain about 40 types of hydrolytic enzymes, including proteases, nucleases, glycosidases, lipases, phospholipases, phosphatases and sulfatases . All are acidic hydrolases. Most of the lysosomal membrane proteins are highly glycosylated, which helps to protect them from the lysosomal proteases in the lumen. A vacuolar H ATPase in the lysosomal membrane uses the energy of ATP hydrolysis to pump H into the lysosome, thereby maintaining the lumen at its acidic pH (PH 5). The three ways that materials are delivered to lysosomes are: phagocytosis, autophagy and endocytosis. In phagocytosis, the plasma membrane surrounds a smaller cell or food particle, forming a structure called phagosome, this structure is delivered to lysosome, where it is digested. During autophagy damaged organelles are surrounded by a membrane and delivered to a lysosome. Endocytosed molecules are initially delivered in vesicles to early endosomes . Then they pass on into late endosomes. Mature lysosomes form by a maturation process from late endosomes.

VESICULAR TRANSPORT: Vesicular transport is an active process in which materials move into or out of the cell enclosed as vesicles. Vesicles are bubble-like structures surrounded by a membrane. They can form at the cell membrane or can fuse with the membrane. Solid particles, droplets of fluid or many molecules at a time can be moved across the membrane in vesicles. There are two basic types of vesicular transport-endocytosi s and exocytosvesicles bud from the ER and COPI-coated vesicles bud from Golgi compartments. Each clathrin subunit consists of three large and three small polypetide chains that form a three-legged structure called a triskelion.
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vSNARE and tSNARESs are thought to have a central role in membrane fusion

EXOCYTOSIS: transport vesicles destined for the plasma membrane normally leave the TGN in a steady stream as irregularly shaped tubules . The fusion of the vesicles with the plasma membrane is called exocytosis . This constitutive secretory pathway operates continuousely .In regulated secretory pathway soluble proteins and other substrates are stored in secretory vesicles for later release. This pathway is found in cells specialized for secreting products rapidly on demand hormones, neurotransmitters, digestive enzymes. ENDOCYTOSIS: By the process of endocytosis cells remove plasma membrane components and deliver them to internal compartments called endosomes, from where they can be recycled to the same or different regions of the plasma membrane or can be delivered to lysosomes for degradation. Cells also use endocytosis to capture important nutrients, such as vitamins, lipids, cholesterol, and iron. The routes that lead inward from the surface of the cell to lysosomes start with process of endocytosis . By this process cells take up macromolecules, particulate substances, and, in specialized cases, even other cells The three types of endocytosis are: pinocytosis or cell-drinking, phagocytosis or cell-eating and receptor-mediated endocytosis In phagocytosis large particles are ingested via large vesicles called phagosomes . In pinocytosis fluid and solutes are ingested via small pinocytic vesicles. Phagocytosis is a triggered processs, that is carried out by specialized cells called professional phagocytes such as macrophages and neutrophils. The triggers of phagocytosis are antibodies. Virtually all eucaryotic cells ingest bits of their plasma membrane in the form of small pinocytic vesicles, which are later returned to the cell surface. This process is called pinocytosis . Since a cells surface area and volume remain unchanged during this process, it is clear that the same amount of plamsa membrane is being added to the cell surface by the converse process of exocytosis. Since extracellular fluid is trapped in clathrin-coated pits as they invaginate to form coated vesicles, any substance dissolved in the extracellular fluid is internalized a process called fluid-phase endocytosis In the process of receptor-mediated endocytosis, the macromolecules bind to complementary transmembrane receptor proteins, accumulate in coated pits and then enter the cell as receptor-macromolecule complexes in clathrin-coated vesicles. More than 25 distinct receptors are known to participate in receptor-mediated endocytosis of different types of molecules. Many animal cells take up cholesterol by receptor-mediated endocytosis . Most cholesterol is transported in the blood as cholesterol esters in the form of lipid-protein particles known as low-density lipoproteins (LDLs). This regulated pathway is disrupted in individuals who inherit defective genes encoding LDL receptors. The resulting high levels of blood cholesterol predispose these individuals to develop atherosclerosis prematurely. In some cases receptors are lacking altogether, in others the receptors are defective PLAMSA MEMBRANE:
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Encloses the cell, Defines its boundaries, Maintains the essential differences between the cytosol and the extracellular environment, Maintains the characteristic differences between the contents of organelles and the cytosol. The lipid bilayer provides the basic structure for all cell membranes. Lipid molecules constitute about 50 % of the mass of most animal cell membranes All of the lipid molecules of cell membranes are amphiphilic : they have a hydrophilic polar end, and a hydrophobic or non-polar end Phospholipids are the most abundant membrane lipids. They have a polar (hydrophilic) had group and two hydrophobic (non-polar) hydrocarbon tails. Tails are fatty acids. One tail typically has one or more cis-double bonds unsaturated, while the other tail does not saturated . Cis-double bond creates a small kink in the tail The main phospholipids in most cell membranes are phosphoglycerides which have a threecarbon glycerol backbone. Phosphatidylethanolamine, phosphatidylserine and phosphatidylcholine are the main ones in mamallian cell membranes. Another important phospholipid is called sphyngomyelin . Eucaryotic plasma membranes contain especially large amounts of cholesterol, which is a sterol. Lipid molecules spontaneousely aggregate to burry their hydrophobic hydrocarbon tails in the interior and expose their hydrophilic heads to water. Being cylindrical phospholipid molecules spontaneousely form bilayers in aqueous environment. One of the most important chararcteristics of membrane is fluidity The fluidity of a lipid bilayer depends on both its composition and its temperature . A shorter chain length reduces the tendency of hydrocarbon chains to interact with one another. Cisdouble bonds produce kinks in hydrocarbon chains that make them more difficult to pack together. The membrane remains fluid at lower temperatures. Cholesterol modulates the properties of lipid bilayers . Cholesterol makes the lipid bilayer less deformable and thereby decreases the permeability of bilayer to small water-soluble molecules . At high concentrations cholesterol also prevents the hydrocarbon chains from coming together and crystallizing Although the lipid bilayer provides the basic structure of biological membranes, the membrane proteins perform most of the membranes specific tasks and therefore give each type of cell membrane its characteristic functional properties. Membrane proteins can be associated with the lipid bilayer in different ways . According to this two types of membrane proteins can be distinguished: integral and peripheral Membrane proteins have a variety of functions. They act as: Transporters, Anchors, Receptors, Enzymes 5 % of lipids of outer monolayer and most of membrane proteins are glycosylated: they are called glycolipids and glycoproteins. The terms cell coat or glycocalyx are sometimes used to describe the carbohydrate-rich zone on the cell surface The functions of glycocalyx are: defensive , cell recognition, cell adhesion

MEMBRANE TRANSPORT: The smaller the molecule and the more soluble it is in oil, the more rapidly it will diffuse across the lipid bilayer . Small nonpolar molecules, such as O2 and CO2, readily dissolve in bilayers and therefore diffuse rapidly across them. Small
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uncharged polar molecules, such as water and urea, also diffuse across a bilayer, albeit much more slowly. By contrast, lipid bilayers are highly impermeable to charged molecules (ions) . Transporters and channels are two major classes of membrane transoprt proteins All channels and many transporters allow the solutes to cross the membrane only passively downhill, a process called passive transport or facilitated diffusion. Chemical or electrochemical gradient drives passive transport. Transporters actively pump certain solutes across the membrane against the electrochemical gradient uphill. This process, known as active transport is mediated by transporters which are also called pumps. Thus transmembrane movement of small molecules mediated by transporters can be either active or passive, whereas that mediated by channels is always passive. Some transporters simply mediate the movement of a single solute from one side of the membrane to the other, they are called uniporters Others function as coupled transporters, in which the transfer of one solute strictly depends on the transport of the second Coupled transport involves either the simultaneous transfer of a second solute in the same direction, performed by symporters (co-transporters), or the transfer of a second solute in the opposite direction performed by antiporters (exchangers) Three types of ATP-driven pumps: P-type pumps multipass transmembrane proteins. They phosphorylate themselves during the pumping cycle (maintain gradients of Na+, K+, H+, Ca+ across the cell membrane) F-type pumps ATP synthase, they use H+ gradient to drive synthesis of ATP ABC transoporters pump small molecules across the cell membranes, unlike Ptype and F-type pumps which exclusively transport ions

Sodium-Potassium Pump Ion Channels Ion channels form hydrophilic pores across membranes. They can not be coupled to an energy source, so the transport is always passive downhill Two main distinctions: Ion channels are ion selective, Ion channels are gated, which allows them to open briefly and then close again The gate opens in response to a stimulus. The known stimuli are:
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The concentration of K+ is typically 10 to 30 times higher inside cells than outside, whereas the reverse is true for Na+ These concentration differences are maintained by Na+ K+ pump or Na+ pump found in the plasma membrane of all animal cells The pump operates as an antiporter, actively pumping Na+ out of the cell against its electrochemical gradient and pumping K+ in The pump hydrolizes ATP to pump Na+ out and K+ in, it is also known as Na+ K+ ATPase

Change in the voltage across the membrane voltage-gated ion channels A mechanical stress mechanically-gated ion channels Some ligand ligand-gated ion channels Water channels - aquaporins allow water move readily across the membrane