Notes Membrane bound organelles PDF

Membrane bound & non-membrane organelles Ardaning Nuriliani Lab. Struktur Perkembangan Hewan Fakultas Biologi Universitas Gadjah Mada  Membranous Organelles completely surrounded by a phospholipid bilayer sim...

Membrane bound & non-membrane organelles Ardaning Nuriliani Lab. Struktur Perkembangan Hewan Fakultas Biologi Universitas Gadjah Mada  Membranous Organelles completely surrounded by a phospholipid bilayer similar to the plasma membrane surrounding the cell isolate of each individual organelle - so that the interior of each organelle does not mix with the cytosol -known as compartmentalization BUT - cellular compartments must “talk” to each other → therefore the cell requires a well-coordinated transport system in order for the organelles to communicate and function together -”vesicular transport” -active process – requires ATP  Membranous Organelles major functions of the organelles 1. protein synthesis – ER & Golgi 2. energy production – mitochondria 3. waste management – lysosomes & peroxisomes  Membranous Organelles the organelles of a eukaryotic cell are not constructed de novo they require information in the organelle itself when a cell divides – it must duplicate its organelles also in general – the cell enlargen existing organelles by incorporating new phospholipids & proteins into them the bigger organelle then divides when the daughter cell divides during cytokinesis  The Endomembrane System: A Review endomembrane system is a complex & dynamic player in the cell’s compartmental organization divides the cell into compartments includes the: Nucleus Endoplasmic Reticulum Golgi apparatus lysosomes, endosomes vacuoles & vesicles  The Endomembrane System: A Review proteins travelling through the ER & Golgi are destined for 1. Secretion outside the cell 2. Plasma membrane 3. Lysosome 1. Endoplasmic reticulum (ER) = series of membrane-bound, flattened sacs in communication with the nucleus and the plasma membrane -each sac or layer = cisternae -inside or each sac = lumen (10% of total cell volume) - with a membrane surface up to 30 times that of the plasma membrane, -distinct regions of the ER are functionally specialized – Rough ER vs. Smooth ER  Endoplasmic Reticulum: Biosynthetic Factory ER: endoplasmic = “within the cytoplasm,” & reticulum is Latin for “little net.” ER → a network of membranous tubules & sacs called cisternae (from the Latin cisterna, a reservoir for a liquid). ER membrane separates the internal compartment of the ER (ER lumen (cavity) or cisternal space), from the cytosol. ER membrane is continuous with the nuclear envelope, the space between the two membranes of the envelope is continuous with the lumen of the ER. Smooth ER: its outer surface lacks ribosomes. Rough ER: studded with ribosomes on the outer surface of the membrane & appears rough through the electron microscope. Ribosomes → also attached to the cytoplasmic side of the nuclear envelope’s outer membrane → continuous with rough ER. 1. Endoplasmic reticulum (ER) -two types: Rough ER - outside studded with ribosomes -continuous with the nuclear membrane -protein synthesis, phospholipid synthesis -also the initial site of processing & sorting of proteins 1. Endoplasmic reticulum (ER) Smooth ER – extends from the RER -free of ribosomes main function is transport vesicle synthesis – area where this happens can be called transitional ER 3 functions of ER: 1. synthesis – phospholipids, lipids, & proteins 2. storage – intracellular calcium 3. transport – site of transport vesicle production  1. Endoplasmic reticulum (ER) -the import of proteins into the RER is a co- translational process -import of proteins into an organelle = translocation -proteins are imported as they are being translated by ribosomes -in contrast to the import of proteins into other organelles (e.g. chloroplasts, mitochondria, peroxisomes) & the nucleus = post-translational process  Co-translational Protein Synthesis 2 kinds of proteins enter the ER: 1. ER proteins – transmembrane proteins that stay stuck in the ER membrane PLUS ER lumen proteins that remain in the ER 2. proteins destined for the Golgi, PM or lysosome or secretion Co-translational Protein Synthesis transport from the ribosome across the ER membrane requires the presence of an ER signal sequence (red in the figure) 16-30 amino acids at the beginning of the peptide sequence (N-terminal)  Co-translational Protein Synthesis a complex of proteins will bind this signal in the cytoplasm = signal recognition particle/SRP the ER membrane has receptor for the SRP and ribosome – SRP receptor (yellow protein in figure) the ribosome is “docked” next to a “hole” in the ER membrane (blue protein in figure) = translocon translocon recognizes the signal sequence and binds it 🡪 “guides” the rest of the translating polypeptide into the ER lumen once the polypeptide is fed into the ER lumen – a peptidase (located in the SRP receptor complex) cleaves the signal sequence off  Translocation try this animation – it might be a bit complicated – but give it a try anyway http://www.rockefeller.edu/pubinfo/proteintarget.html here’s a figure from a molecular biology text that summarizes the process  once the polypeptide is fed into the ER lumen – a peptidase cleaves the signal sequence off = PRODUCES A SOLUBLE PROTEIN localizes to the ER lumen the presence of another sequence of amino acids within the polypeptide – stop-transfer sequence – the translocator stops translocating and transfers the polypeptide into the ER membrane = PRODUCES A TRANSMEMBRANE PROTEIN  Modifications in the RER 1. folding of the peptide chain actually a spontaneous process – due to the side chains on the amino acids only properly folded proteins get transported to the Golgi for additional processing and transport many proteins located in the ER which supervise this folding 2. formation of disulfide bonds help stabilize the tertiary and quaternary structure of proteins 3. breaking of specific peptide bonds – proteolytic cleavage or proteolysis 4. assembly into multimeric proteins (more than one chain)  Modifications in the RER 5. addition and processing of carbohydrates = glycosylation N-linked glycosylation = attachment of 14 sugar residues as a group to an asparagine amino acid within the protein the sugar is actually built and then transferred as one unit to the nearby translating protein by a transferase protein needs to be trimmed down in order to allow protein folding most proteins made in the ER undergo N-linked glycosylation but other cell types have SER with enzymes embedded in it for additional functions: 1. lipid and steroid biosynthesis for membranes 2. detoxification of toxins and drugs 3. cleaves glucose so it can be released into the bloodstream 4. uptake and storage of calcium  Functions of Smooth ER Smooth ER functions diverse & vary with cell type. Smooth ER functions: synthesis of lipids, metabolism of carbohydrates, detoxification of drugs and poisons, and storage of calcium ions. Enzymes of the smooth ER are important in the synthesis of lipids, including oils, steroids, and new membrane phospholipids. Functions of Rough ER Many cells secrete proteins that are produced by ribosomes attached to rough ER. For instance, certain pancreatic cells synthesize the protein insulin in the ER and secrete this hormone into the bloodstream. rough ER is a membrane factory for the cell; it grows in place by adding membrane proteins & phospholipids to its own membrane. Like smooth ER, rough ER also makes membrane phospholipids; enzymes built into the ER membrane assemble phospholipids from precursors in the cytosol.  Rough Endoplasmic Reticulum Rough endoplasmic reticulum (RER): prominent in cells specialized for protein secretion, such as pancreatic acinar cells (making digestive enzymes), fibroblasts (collagen), and plasma cells (immunoglobulins). Major function of RER: production of membrane associated proteins. Proteins synthesized in the RER can have several destinations: - intracellular storage (eg, in lysosomes & specific granules of leukocytes), - provisional storage in cytoplasmic vesicles prior to exocytosis (eg, in the pancreas, some endocrine cells), - integral membrane proteins.  MEDICAL APPLICATION Quality control during protein production in the RER & properly functioning ERAD to dispose of defective proteins are extremely important & several inherited diseases result from malfunctions in this system. Ex: in some forms of osteogenesis imperfecta bone cells synthesize & secrete defective procollagen molecules that cannot assemble properly & produce very weak bone tissue.  Smooth Endoplasmic Reticulum Lacking polyribosomes, SER is not basophilic → best seen with the TEM. SER cisternae are more tubular or saclike, with interconnected channels of various shapes & sizes rather than stacks of flattened cisternae. 3 main functions, which vary in importance in different cell types. Enzymes in the SER perform synthesis of phospholipids and steroids, major constituents of cellular membranes. Other SER enzymes, including those of the cytochrome P450 family, allow detoxification of potentially harmful exogenous molecules such as alcohol, barbiturates, & other drugs. In liver cells, these enzymes also process endogenous molecules such as the components of bile. SER vesicles → responsible for sequestration & controlled release of Ca2+, which is part of the rapid response of cells to various stimuli. This function is particularly well developed in striated muscle cells, where the SER has an important role in the contraction process and assumes a specialized form called the sarcoplasmic reticulum.  MEDICAL APPLICATION Jaundice denotes a yellowish discoloration of the skin and is caused by accumulation in extracellular fluid of bilirubin & other pigmented compounds, which are normally metabolized by SER enzymes in cells of the liver & excreted as bile. A frequent cause of jaundice in newborn infants is an underdeveloped state of SER in liver cells, with failure of bilirubin to be converted to a form that can be readily excreted.  2. Ribosomes = can be considered a non-membranous organelle, thus are not considered organelles, made in the nucleolus 2 protein subunits in combination with rRNA: -large subunit = 28S rRNA, 5.8S rRNA, 5 rRNA + 50 proteins -small subunit = 18S rRNA + 33 proteins proteins are translating in the cytoplasm & imported into the nucleus rRNA is transcribed in the nucleolus ribosomes found in association with the ER = where the peptide strand is fed into from the ribosome also float freely within the cytoplasm as groups = polyribosomes  Ribosomes: Protein Factories Ribosomes, which are complexes made of ribosomal RNAs and proteins →carry out protein synthesis. Cells with high rates of protein synthesis have particularly large numbers of ribosomes as well as prominent nucleoli Ribosomes build proteins in two cytoplasmic regions: Free ribosomes are suspended in the cytosol, while bound ribosomes are attached to the outside of the endoplasmic reticulum or nuclear envelope. Bound and free ribosomes are structurally identical, and ribosomes can play either role at different times. Most of the proteins made on free ribosomes function within the cytosol; examples are enzymes that catalyze the first steps of sugar breakdown. Bound ribosomes generally make proteins that are destined for insertion into membranes, for packaging within certain organelles such as lysosomes, or for export from the cell (secretion).  Ribosom Ribosomes: macromolecular machines, about 20 × 30 nm in size, which assemble polypeptides from amino acids on molecules of transfer RNA (tRNA) in a sequence specified by mRNA. A functional ribosome has two subunits of different sizes bound to a strand of mRNA. The core of the small ribosomal subunit is a highly folded ribosomal RNA (rRNA) chain associated with more than 30 unique proteins; the core of the large subunit has three other rRNA molecules and nearly 50 other basic proteins. rRNA molecules in the ribosomal subunits not only provide structural support but also position transfer RNAs (tRNA) molecules bearing amino acids in the correct “reading frame” & catalyze the formation of the peptide bonds. The more peripheral proteins of the ribosome seem to function primarily to stabilize the catalytic RNA core. These ribosomal proteins are themselves synthesized in cytoplasmic ribosomes, but are then imported to the nucleus where they associate with newly synthesized rRNA. 3. Golgi Apparatus = stacks of membranes called cisternae (cisterna, singular) -the first sac in the stack = cis-face (faces the ER) -the last sac in the stack = trans-face -the ones in the middle = medial cisterna or cisternae Named after Camillo Golgi in 1897 3. Golgi Apparatus - associated with the cis & trans faces are additional networks of interconnected cisternal structures - called the cis Golgi network (CGN) and trans Golgi network (TGN) - the TGN has a critical role in protein sorting  3. Golgi Apparatus site of final protein modification and packaging of the finished protein functions: 1. protein modification A. glycosylation - creation of glycoproteins and proteoglycans B. site for phosphate addition to proteins = phosphorylation C. protein trimming 2. production of sugars Golgi makes many kinds of polysaccharides 3. formation of the lysosome 4. packaging of proteins and transport to their final destination TGN acts as a sorting station for transport vesicles  Modifications in the Golgi glycosylation = produces a glycoprotein or a proteoglycan most plasma membrane and secreted proteins have one or more carbohydrate chains sugars help target proteins to their correct location; are important in cell-cell and cell-matrix interactions two kinds: N-linked and O linked O-linked sugars are added one at a time in the Golgi to the amino acids serine, threonine or lysine (usually one to four saccharide subunits total) N-linked sugars are added as a group (about 14 sugars!) in the ER Proteoglycan  glycosylation: glycosylation starts in the ER N-linked glycosylation – addition of N-linked oligosaccharides many of these N-linked sugar residues are trimmed off within the ER important for folding of the protein glycosylation continues in the cisternae of the Golgi addition of O-linked oligosaccharides to proteins PLUS modification of the N-linked oligosaccharides - either addition or removal of sugar residues  Why Glycosylation? the vast abundance of glycoproteins suggests that glycosylation has an important function N-linked is found in all eukaryotes – including single-celled yeasts a type of N-linked can even be found in archaea – in their cell walls WHY GLYCOSYLATION? N-linked in the ER is important for proper protein folding N-linked also limits the flexibility of the protein the sugar residues can prevent the binding of pathogens sugar residues also function as signaling chemicals sugar residues function in cell interactions  Why Glycosylation? O-linked glycosylation O-linked are added one at a time in the Golgi to the amino acids serine, threonine or lysine (one to four saccharide subunits total) added on by enzymes called glycosyltransferases human A, B and O antigens are sugars added onto proteins and lipids in the plasma membrane of the RBC everyone has the glycosyltransferase needed to produce the O antigen those with blood type A have an additional Golgi glycosyltransferase enzyme which modifies the O antigen to make the A antigen a different glycosyltransferase is required to make the B antigen both glycosyltransferases are required for the creation of the AB antigen coded for by specific gene alleles on chromosome 9 (ABO locus) Modifications in the Golgi: Protein Trimming some plasma membrane proteins and most secretory proteins are synthesized as larger, inactive pro-proteins that will require additional processing to become active this processing occurs very late in maturation ◦ processing is catalyzed by protein-specific enzymes called proteases ◦ some proteases are unique to the specific secretory protein ◦ trimming occurs in secretory vesicles that bud from the trans-Golgi face ◦ processing could be at one site (albumin) – other proteins may require more than one peptide bond (insulin) The Golgi: Protein transport within the cytoplasm protein transport within the cell is tightly regulated most proteins usually contain “tag” or signals that tell them where to go in the Golgi - specific sequences within a protein will cause: 1. retention in the Golgi 2. will target it to lysosomes 3. send it to the PM for fusion 4. send it to the PM for secretion a lack of a signal means you will automatically be secreted = constitutive secretion  SO - WHERE DO PROTEINS GO AFTER THE GOLGI??? - proteins budding off the Golgi have three targets: targets: 1. secretory vesicles for exocytosis 2. membrane vesicles for incorporation into plasma membrane 3. transport vesicles for the lysosome WHAT IF YOU AREN’T ONE OF THESE PROTEINS?? ER proteins stay in the ER ◦ never traffic to the Golgi ◦ these ER proteins will have a retention signal Ribosomal proteins ◦ translation of ribosomal proteins are done in the cytoplasm by polyribosomes ◦ assembled into the large and small protein subunits in the cytoplasm ◦ imported into the nucleus ◦ rRNAs are transcribed in the nucleolus - no translation!!! ◦ protein subunits and rRNAs are assembled in the nucleolus to form the small and large ribosomal subunits – exported from nucleus mitochondrial proteins ◦ the mitochondria has its own DNA, transcribes its own mRNA and has its own ribosomes for translation  The Golgi Apparatus: Shipping & Receiving Center Golgi is a warehouse for receiving, sorting, shipping, & even some manufacturing. Products of the ER, such as proteins, are modified & stored and then sent to other destinations. Golgi apparatus is especially extensive in cells specialized for secretion. Golgi apparatus consists of a group of associated, flattened membranous sacs—cisternae—looking like a stack of pita bread. A cell may have many, even hundreds, of these stacks. Membrane of each cisterna in a stack separates its internal space from the cytosol. Vesicles concentrated in the vicinity of the Golgi apparatus are engaged in the transfer of material between parts of the Golgi & other structures. A Golgi stack has a distinct structural directionality, with the membranes of cisternae on opposite sides of the stack differing in thickness and molecular composition. 2 sides of a Golgi stack → cis face & trans face; these act, respectively, as the receiving and shipping departments of the Golgi apparatus. Cis means “on the same side,” & cis face is usually located near the ER. Transport vesicles move material from the ER to the Golgi apparatus. A vesicle that buds from the ER can add its membrane & the contents of its lumen to the cis face by fusing with a Golgi membrane on that side. Trans face (“on the opposite side”) gives rise to vesicles that pinch off and travel to other sites. Golgi function producing a large variety of carbohydrates. Membrane phospholipids alteration. Manufactures some macromolecules. Many polysaccharides secreted by cells are Golgi products. The Golgi manufactures and refines its products in stages, with different cisternae containing unique teams of enzymes.  Apparatus Golgi named after histologist Camillo Golgi (1898). consists of many smooth membranous saccules, some vesicular, others flattened, but all containing enzymes and proteins being processed. In most cells the small Golgi complexes are located near the nucleus. Golgi saccules at sequential locations contain different enzymes at different cis, medial, & trans levels. Enzymes of the Golgi apparatus are important for glycosylation, sulfation, phosphorylation, & limited proteolysis of proteins. Golgi apparatus initiates packaging, concentration, & storage of secretory products.  Secretory Granules Originating as condensing vesicles in the Golgi apparatus Secretory granules are found in cells that store a product until its release by exocytosis is signaled by a metabolic, hormonal, or neural message (regulated secretion). The granules are surrounded by the membrane & contain a concentrated form of the secretory product. The contents of some secretory granules may be up to 200 times more concentrated than those in the cisternae of the RER. Secretory granules with dense contents of digestive enzymes are also referred to as zymogen granules. 4. Lysosomes = “garbage disposals” - dismantle debris, eat foreign invaders/viruses taken in by endocytosis or phagocytosis - also destroy worn cellular parts from the cell itself and recycles the usable components = autophagy - form by budding off the trans-Golgi network?? - cell biologists not really sure exactly how the lysosome forms  4. Lysosomes - contains powerful enzymes to breakdown substances into their component parts - over 40 kinds of hydrolytic enzymes - these enzymes are collectively known as acid hydrolases - acidic interior - critical for function of these enzymes - the hydrolytic enzymes of the lysosome need to be cleaved first in order to become enzymatically active - done by the acidity of the lysosomes interior - acidic interior created and maintained by a hydrogen pump (H+ ATPase) that pumps H+ into the interior - Active transport - chloride ions that diffuse in passively through a chloride channel - forms hydrochloric acid (HCl) 4. Lysosomes several different kinds of lysosomes – diverse in shape & size types: lysosome – form from the budding and fusion of vesicles from the TGN these vesicles contain lysosomal enzymes early endosome – forms through receptor-mediated endocytosis from the plasma membrane late endosome – forms by fusion of early endosomes with vesicles containing lysosomal enzymes endolysosome – fusion of a late endosome with a pre-existing lysosome transforms it into a lysosome an endolysosome may be considered an immature lysosome Lysosomes: Digestive Compartments A lysosome is a membranous sac of hydrolytic enzymes that many eukaryotic cells use to digest (hydrolyze) macromolecules. Lysosomal enzymes work best in the acidic environment found in lysosomes. How are the proteins of the inner surface of the lysosomal membrane & the digestive enzymes themselves spared from destruction? Apparently, the three-dimensional shapes of these proteins protect vulnerable bonds from enzymatic attack. Lysosomes carry out intracellular digestion in a variety of circumstances. Amoebas & many other unicellular protists eat by engulfing smaller organisms or food particles, a process called phagocytosis (from the Greek phagein, to eat, and kytos, vessel, referring here to the cell). The food vacuole formed in this way then fuses with a lysosome, whose enzymes digest the food. Digestion products, including simple sugars, amino acids, and other monomers, pass into the cytosol and become nutrients for the cell. Some human cells also carry out phagocytosis. Among them are macrophages, a type of white blood cell that helps defend the body by engulfing and destroying bacteria and other invaders.  Lysosomes → use their hydrolytic enzymes to recycle the cell’s own organic material (autophagy). During autophagy, a damaged organelle or small amount of cytosol becomes surrounded by a double membrane (of unknown origin), & a lysosome fuses with the outer membrane of this vesicle. Lysosomal enzymes dismantle the inner membrane & the enclosed material → the resulting small organic compounds are released to the cytosol for reuse. A human liver cell → recycles half of its macromolecules each week. Cells of people with inherited lysosomal storage diseases lack a functioning hydrolytic enzyme normally present in lysosomes. Lysosomes become engorged with indigestible material, which begins to interfere with other cellular activities. Tay-Sachs disease → a lipid-digesting enzyme is missing or inactive, the brain becomes impaired by an accumulation of lipids in the cells. Diseases at the Organelle Level Tay Sachs and lysosomes: also known a Hexosaminidase A deficiency - named after Waren Tay and Bernard Sachs - key identifying mark = cherry red spot in the retina - lack one of the 40 lysosomal enzymes – hexosaminidase - results in the accumulation of gangliosides (phospholipid) in the cell membrane of neurons - death of the neuron results 🡪 failure of nervous system communication - infantile form of the disease = death by 4 yrs - juvenile form = death from 5 to 15 yrs - adult onset – not fatal; progressive loss of nervous function - most common in Ashkenazi Jews, French Canadians and Cajun populations in Lousiana (same mutation as Jews)  Proteasome very small abundant protein complexes that are not associated with membrane, each approximately the size of the small ribosomal subunit. Function to degrade denatured or otherwise nonfunctional polypeptides. Remove proteins no longer needed by the cell and provide an important mechanism for restricting the activity of a specific protein to a certain window of time. Whereas lysosomes digest organelles or membranes by autophagy, proteasomes deal primarily with free proteins as individual molecules. Proteasome is a cylindrical structure made of four stacked rings, each composed of seven proteins including proteases. At each end of the cylinder is a regulatory particle that contains ATPase and recognizes proteins with attached molecules of ubiquitin, an abundant cytosolic 76-amino acid protein found in all cells. Misfolded or denatured proteins, or short-lived proteins with oxidized amino acids, are recognized by chaperones and targeted for destruction by other enzyme complexes that conjugate ubiquitin to lysine residues of the protein, followed by formation of a polyubiquitin chain. Ubiquinated proteins are recognized by the regulatory particles of proteasomes, unfolded by the ATPase using energy from ATP, and then translocated into the core of the cylindrical structure and degraded by endopeptidases. The ubiquitin molecules are released for reuse and the peptides produced may be broken down further to amino acids or they may have other specialized destinations, such as the antigen-presenting complexes of cells activating an immune response.  MEDICAL APPLICATION Failure of proteasomes or other aspects of a cell’s protein quality control can allow large aggregates of protein to accumulate in affected cells. Such aggregates may adsorb other macromolecules to them & damage or kill cells. Aggregates released from dead cells can accumulate in the extracellular matrix of the tissue. In the brain this can interfere directly with cell function and lead to neurodegeneration. Alzheimer’s disease & Huntington’s disease are two neurologic disorders caused initially by such protein aggregates  5. Mitochondria -surrounded by a dual phospholipid bilayer an outer mitochondrial membrane an inner mitochondrial membrane a fluid-filled space = mitochondrial matrix (contains ribosomes!) - the inner membrane is folded into folds called cristae - these increase the membrane surface area for the enzymes of Oxidative Phosphorylation  outer membrane - 50% phospholipid & 50% protein -very permeable - contains pores for the import and export of critical materials inner membrane - 20% phospholipid & 80% protein -less permeable vs. the outer membrane -folded extensively to form partitions = cristae -contains proteins that work to create an electrochemical gradient -contains enzymes that use this gradient for the synthesis of ATP -also contains pumps to move ATP into the cytosol matrix - lumen of the mitochondria - breakdown of glucose into water and CO2 ends here (enzymes of the Transition phase Kreb’s Cycle) Cellular Respiration -glycolysis -transition phase -citric acid cycle -electron transport chain http://biology.about.com/gi/dynamic/offsite.htm?site=http://www.sp.uconn.edu/%7Eterry/images/anim/ETS.html http://biology.about.com/gi/dynamic/offsite.htm?site=http://www.biocarta.com/pathfiles/krebPathway.asp http://vcell.ndsu.nodak.edu/animations/etc/movie.htm 6. Peroxisomes: found in all cells but abundant in liver and kidney cells - only identified in 1954 - may arise from pre-existing peroxisomes or may bud from the ER - major function is oxidation (breakdown) of long chain fatty acids (beta-oxidation) - results in the conversion of the fatty acid into acetyl coA 🡪 Kreb’s cycle - in plant cells – beta-oxidation is only done by the peroxisome - in animal cells – the mitochondria can also perform this reaction - oxidation is done by oxidases = enzymes that use oxygen to oxidize substances - remove hydrogen atoms from the fatty acid - this reaction generates hydrogen peroxide (H2O2)  6. Peroxisomes: found in all cells but abundant in liver and kidney cells PROBLEM #1: H2O2 is very corrosive - therefore peroxisomes also contain an enzyme called catalase to break this peroxide down into water and oxygen PROBLEM #2: the electron transport chain in mitochondria produces superoxide radicals (O2-) as a normal consequence of electron “leaking” (from complex I) - peroxisomes also contain anti-oxidant enzymes to break down other dangerous oxidative chemicals made by the cell during metabolism e.g. SOD – breaks down O2- to make H2O2 -other functions of peroxisomes: 1. synthesis of bile acids 2. breakdown of alcohol by liver cells Adrenoleukodystrophy and peroxisomes: -X linked disorder in the gene ABCD1 (transporter protein) -1:20,000 to 1:50,000 births -in ALD - peroxisomes lack an essential enzyme -leads to a build up of a long-chain saturated fatty acids on cells of throughout the body -can results in the loss of the myelin sheath – not known why -lethargy, skin darkens, blood sugar drops, altered heart rhythm imbalanced electrolytes, paralysis, death *** slowed by a certain triglyceride found in rapeseed oil Lorenzo Odone = “Lorenzo’s Oil” (mixture of unsaturated fatty acids that slows the development of these saturated FAs) F-actin and  Peroxisomes: Oxidation specialized metabolic compartment bounded by a single membrane. Peroxisomes contain enzymes that remove hydrogen atoms from various substrates and transfer them to oxygen (O2), producing hydrogen peroxide (H2O2) as a by-product (from which the organelle derives its name). Some peroxisomes use oxygen to break fatty acids down into smaller molecules that are transported to mitochondria and used as fuel for cellular respiration. Peroxisomes in the liver detoxify alcohol and other harmful compounds by transferring hydrogen from the poisonous compounds to oxygen. The H2O2 formed by peroxisomes is itself toxic, but the organelle also contains an enzyme that converts H2O2 to water. This is an excellent example of how the cell’s compartmental structure is crucial to its functions: The enzymes that produce H2O2 and those that dispose of this toxic compound are sequestered away from other cellular components that could be damaged. Specialized peroxisomes called glyoxysomes are found in the fat-storing tissues of plant seeds. These organelles contain enzymes that initiate the conversion of fatty acids to sugar, which the emerging seedling uses as a source of energy and carbon until it can produce its own sugar by photosynthesis. Peroxisomes grow larger by incorporating proteins made in the cytosol and ER, as well as lipids made in the ER and within the peroxisome itself. But how peroxisomes increase in number and how they arose in evolution—as well as what organelles they are related to—are still open questions Vacuoles: Diverse Maintenance Compartments Vacuoles are large vesicles derived from the endoplasmic reticulum and Golgi apparatus. Thus, vacuoles are an integral part of a cell’s endomembrane system. Like all cellular membranes, the vacuolar membrane is selective in transporting solutes; as a result, the solution inside a vacuole differs in composition from the cytosol. Vacuoles perform a variety of functions in different kinds of cells. Food vacuoles, formed by phagocytosis, have already been mentioned (see Figure 6.13a). Many unicellular protists living in fresh water have contractile vacuoles that pump excess water out of the cell, thereby maintaining a suitable concentration of ions and molecules inside the cell (see Figure 7.13). In plants and fungi, certain vacuoles carry out enzymatic hydrolysis, a function shared by lysosomes in animal cells. (In fact, some biologists consider these hydrolytic vacuoles to be a type of lysosome.) In plants, small vacuoles can hold reserves of important organic compounds, such as the proteins stockpiled in the storage cells in seeds. Vacuoles may also help protect the plant against herbivores by storing compounds that are poisonous or unpalatable to animals. Some plant vacuoles contain pigments, such as the red and blue pigments of petals that help attract pollinating insects to flowers  Mature plant cells generally contain a large central vacuole (Figure 6.14), which develops by the coalescence of smaller vacuoles. The solution inside the central vacuole, called cell sap, is the plant cell’s main repository of inorganic ions, including potassium and chloride. The central vacuole plays a major role in the growth of plant cells, which enlarge as the vacuole absorbs water, enabling the cell to become larger with a minimal investment in new cytoplasm. The cytosol often occupies only a thin layer between the central vacuole and the plasma membrane, so the ratio of plasma membrane surface to cytosolic volume is sufficient, even for a large plant cell. Peroxisomes Spherical organelles enclosed by a single membrane & named for their enzymes producing & degrading hydrogen peroxide, H2O2. Oxidases located here oxidize substrates by removing hydrogen atoms that are transferred to molecular oxygen (O2), producing H2O2. Peroxidases such as catalase immediately break down H2O2, which is potentially damaging to the cell. These enzymes also inactivate various potentially toxic molecules, including some prescription drugs, particularly in the large and abundant peroxisomes of liver and kidney cells. Other diverse enzymes in peroxisomes complement certain functions of the SER and mitochondria in the metabolism of lipids and other molecules. Thus, the β-oxidation of long-chain fatty acids (18 carbons and longer) is preferentially accomplished by peroxisomal enzymes that differ from their mitochondrial counterparts. Certain reactions leading to the formation of bile acids & cholesterol also occur in peroxisomes. Peroxisomes form in two ways: budding of precursor vesicles from the ER or growth and division of preexisting peroxisomes. Peroxisomal proteins are synthesized on free polyribosomes and have targeting sequences of amino acids at either terminus recognized by receptors located in the peroxisomal membrane for import into the organelle.