The endomembrane system is composed of different membranes that are suspended in the cytoplasm within an eukaryotic cell. These membranes divide the cell into functional and structural compartments, or organelles. In eukaryotes the organelles of the endomembrane system include: the nuclear membrane, the endoplasmic reticulum, the Golgi apparatus, lysosomes, peroxisome. The system is defined more accurately as the set of membranes that form a single functional and developmental unit, either being connected directly, or exchanging material through vesicle transport.
The ribosome is a complex molecular machine, which can be found in all living cells, serving as the site of biological protein synthesis (translation). Ribosomes bind to a messenger RNA chain and use its sequence to determine the correct sequence of amino acids. Amino acids are selected, collected, and carried to the ribosome by transfer RNA (tRNA) molecules, which enter ribosome and bind to the messenger RNA chain. It is during this binding that the correct translation of nucleic acid sequence to amino acid sequence occurs. For each coding triplet in the messenger RNA (mRNA), there is a distinct tRNA which can match and carry the correct amino acid for the coding triplet. The attached amino acids are then linked together by another part of the ribosome.
A ribosome is made from of RNAs and proteins and is therefore a ribonucleoprotein complexes. Each ribosome consists of two components: the small ribosomal subunit, which binds and reads the RNA, and the large subunit, which joins amino acids to form a polypeptide chain. Each subunit is composed of many ribosomal RNA (rRNA) molecules and a variety of ribosomal proteins (r-protein or rProtein). The ribosomes and associated molecules are also known as the translational apparatus.
The ribosome existing in prokaryotic cells is 70S, while in eukaryotic cells is 80S. The size of ribosome is represented by S, S means settlement coefficient, it refers to the sedimentation velocity of matter under the effects of centrifugal force. The bigger molecular weight and particle are, the bigger the S is.
Ribosomes are the workplaces of protein synthesis, the process of translating mRNA into protein. The mRNA comprises a series of codons that dictate to the ribosome the sequence of the amino acids needed to make the protein. Using the mRNA as a template, the ribosome traverses each codon (3 nucleotides)of the mRNA, pairing it with the appropriate amino acid provided by an aminoacyl-tRNA. Aminoacyl-tRNA contains a complementary anticodon on one end and the appropriate amino acid on the other. For fast and accurate recognition of the appropriate tRNA, the ribosome utilizes large conformational changes (conformational proof reading). The small ribosomal subunit, typically bound to an aminoacyl-tRNA containing the amino acid methionine, binds to an AUG codon on the mRNA and recruits the large ribosomal subunit. The ribosome contains three RNA binding sites, designated A, P and E. The A site binds an aminoacyl-tRNA; the P site binds a peptidyl-tRNA (a tRNA bound to the peptide being synthesized); and the E site binds a free tRNA before it exits the ribosome. Protein synthesis begins at a start codon AUG near the 5' end of the mRNA. mRNA binds to the P site of the ribosome first.
There are four activity sites in individual ribosome, which have functions of specific identification in the process of protein synthesis.
Aminoacyl site (A site): it is a site where accepts aminoacy-tRNA that exits in large subunits, it is called aminoacy-tRNA binding site.
Peptidyl site (P site): it is a site where combines peptidyl-tRNA that exits in small subunit, it is peptidyl-tRNA binding site.
Transpeptidase activity site: it is a site with transpeptidase activity that exits in large subunit. It can catalyze the formation of peptide bond between amino acids during peptide chains elongation.
GTP enzyme activity site: it is a site with GTP enzyme activity that exits in large subunits. It can catalyze the decomposition of GTP and provide energy for peptidyl-tRNA, so as to transfer peptidyl-tRNA from A site to P site.
Ribosome is the site of protein synthesis, its function is to translate the genetic information of mRNA that transcribe from DNA into protein. Large and small ribosomal subunits, which are generally free, become monosomes when large subunits combine with small subunits. In the process of protein synthesis, multiple monosomes are bound to an mRNA molecule, arranging in a string and forming polyribosome-the site of protein synthesis. Polyribosome is able to synthesize many identical polypeptide chains at the same time so that improve the efficiency of protein translation.
In cells, large and small ribosomal subunits, monosome and polyribosome are in a dynamic balance of continuous polymerization and depolymerization. During polymerization and depolymerization, polyribosome implements its function, and after the effect, monosome is depolymerized into large and small subunits.
The processes of synthesizing polypeptide chain are as follows:
Initiation: mRNA is the template of synthesizing polypeptide chain, tRNA is a tool for recognizing codons and transferring corresponding amino acid, ribosome is assembly machine for peptide chain. To begin with, mRNA gets into cytoplasm from nucleus and becomes the template of synthesizing peptide chain. Next, the small subunit and mRNA initiate site bond together, initiation codon AUG in the mRNA is recognized by the anticodon of tRNA, which is from DL-Methionine-tRNA (prokaryotic code) or formyl methionine-tRNA (eukaryotic code). Anticodon combines complimentarily with initiation codon AUG, then the large subunit follows on and finally form translation initiation complex.
Elongation: amino acid, which is the raw material for the synthesis of protein, combines with specific tRNA, and then aminoacyl-tRNA complex is formed. tRNA uses anticodon of anticodon loop to recognize the codon and transfers corresponding amino acid to ribosome so that they can synthesize peptide chain.
(1) Registration: ribosome can accommodate two codons at a time. After the translation initiation complex formation, homologous aminoacyl-tRNA (such as alanyl-tRNA) of the second codon gets into A site (aminoacyl site) of ribosome, and codon GCG complementation fixation with anticodon CGC as well.
(2)Transpeptidation: the join keys between amino acid and tRNA in the P site are interrupted under the action of polypeptide chain transferase (transpeptidase), thus the amino acid that carried by tRNA in the P site transfers to A site and forms dipeptide with peptide bond by the means of connecting to the amino acid that located in A site. Transfer RNA (tRNA) leaves P site for cytoplasm, it can carry amino acid again and form the new aminoacyl-tRNA complexes.
(3)Translocation: ribosome moves forward a codon along mRNA.
(4)Ribosome circulation: after ribosome translocation, new codon is in A site of ribosome again, new aminoacyl-tRNA(seryl-tRNA) enters A site. And then under the action of transpeptidase, manufactural dipeptide combines with amino acid of A site, thereby forming tripeptide. Transfer RNA of P site release and ribosome move forward a codon along mRNA. The process makes progress step by step and repeatedly circulates in this way, thus nucleotide sequence of mRNA transforms into amino acid sequence and peptide chain elongation.
Termination and release: the extension of the peptide chain is not unlimited. No corresponding amino acids are transported into ribosome when termination codon (UAG, UGA, UAA) appear in messenger RNA (mRNA), and therefore peptide chains synthesis stop. Synthetic polypeptide chain and tRNA detach under the action of hydrolysis, and then they are released along the centre tube of large subunit and take off finally. At the same time, mRNA separates from large and small subunits, which are able to combine with initiation codon, and free in cytoplasm or be degraded as well. Messenger RNA (mRNA) is degraded too.
(1)Free ribosome: can move about anywhere in the cytosol, but are excluded from the cell nucleus and other organelles. Proteins that are formed from free ribosomes are released into the cytosol and used within the cell (nucleus, mitochondrion, peroxisome).
(2)Membrane-bound ribosomes: When ribosome begins to synthesize some type of proteins, the ribosome can become “membrane-bound”. In eukaryotic cells this happens in a region of the endoplasmic reticulum (ER) called the “rough ER”. The newly produced polypeptide chains are inserted directly into the ER and are then transported to their destinations, through the secretory pathway. Bound ribosomes usually produce secretory protein, lysosome protein, retention protein in ER, and proteins that are used within the plasma membrane.
A polyribosome(or polysome)is a complex of an mRNA molecule and two or more ribosomes that act to translate mRNA instructions into polypeptides. These multiple initiations mean that many more protein molecules can be made in a given time than would be possible if each had to be completed before the next could start. Both free ribosome and membrane-bound ribosome exist in the form of polyribosome during the process of protein translation.
The endoplasmic reticulum (ER) is a network of membrane-enclosed tubules and sacs(cisternae)that extends from the nuclear membrane throughout the cytoplasm. The entire endoplasmic reticulum is enclosed by a continuous membrane and is the largest organelle of most eukaryotic cells. Its membrane may account for about half of all cell membranes.
Lipid account for 1/3 and protein account for 2/3
There are two types of endoplasmic reticulum: rough ER and smooth ER.
(1)Rough Endoplasmic Reticulum (rER)
Membrane-bound ribosomes coat the surface of the ER, creating regions termed rough endoplasmic reticulum, or rough ER. The number of rER existing in cells is associated with cell type, physiological status and differentiation digree. For example, rER is enriched in exocrine pancreas with exuberant secretion function, whereas rER becomes much less when resting stage of secretion. In undifferentiated and immature cells, for example, embryonic cells, stem cells and cultured cells, the number of rER is much less than corresponding normal mature cells.
(2)Smooth Endoplasmic Reticulum (sER)
Regions of ER that lack bound ribosomes are called smooth endoplasmic endoplasmic, or smooth ER. The smooth ER is especially abundant in mammalian liver and gonad cells.
The function of rER is involved in protein synthesis, protein folding and processing, protein packaging and transportation.
(1) Participating in protein synthesis:
The proteins synthesized in rER include secreted proteins（enzyme, antibody）,
membrane proteins, lysosome proteins and ER resident proteins.
Since the chemical composition and structure of both rER and sER are the same, then in the process of protein synthesis, why attatched ribosome can bind to ER, but dissociative ribosome cannot?
In 1975, G.blbel and D.sabatini proposed signal sequence hypothesis, which can explain the mechanism that signal peptide leads ribosome to combine with ER membrane.
The signal sequences span about 20 amino acids, including a stretch of hydrophobic residues, usually at the amino terminus of the polypeptide chain. As they emerge from the ribosome, signal sequences are recognized and bound by a signal recognition particle (SRP) consisting of six polypeptides and a small cytoplasmic RNA (7SL RNA). SRP binds the ribosome as well as the signal sequence, inhibiting further translation and targeting the entire complex (the SRP, ribosome, and growing polypeptide chain) to the rough ER by binding to the SRP receptor on the ER membrane. Binding to the receptor releases the SRP from both the ribosome and the signal sequence of the growing polypeptide chain. The ribosome then binds to a protein translocation complex in the ER membrane, and the signal sequence is inserted into a membrane channel. In both yeast and mammalian cells, the translocation channels through the ER membrane are complexes of three transmembrane proteins, called the Sec61 proteins. Transfer of the ribosome from the SRP to the Sec61 complex allows translation to resume, and the growing polypeptide chain is transferred directly into the Sec61 channel and across the ER membrane as translation proceeds. Thus, the process of protein synthesis directly drives the transfer of growing polypeptide chains through the Sec61 channel and into the ER. As translocation proceeds, the signal sequence is cleaved by signal peptidase and the polypeptide is released into the lumen of the ER.
(2) Protein Folding and Processing:
The ER is also the site of protein folding, assembly of multisubunit proteins, disulfide bond formation. Indeed, the primary role of lumenal ER proteins is to catalyze the folding and assembly of newly translocated polypeptides with the help of molecular chaperones and transport synthesized proteins in vesicles to the Golgi apparatus. Correct folding of newly made proteins is made possible by several endoplasmic reticulum chaperone proteins, including protein disulfide isomerase (PDI), ERp29, the Hsp70 family member BiP/Grp78, calnexin,calreticulin, and the peptidylpropyl isomerase family. Only properly folded proteins are transported from the rough ER to the Golgi apparatus -unfolded proteins cause an unfolded protein response as a stress response in the ER.
(3) Protein glycosylation:
Glycosylation is the process by which monosaccharide or oligosaccharide covalently bound with protein to form glycoprotein. Only N-linked glycosylation can be accomplished in rER lumen, and glycosylation can be eventually finished in golgi apparatus.
The marker enzyme of ER is glucose-6-phosphatase.
(3) Packaging and transport
Proteins Leave the ER in COPII-coated Transport Vesicles
To initiate their journey along the biosynthetic-secretory pathway, proteins that have entered the ER and are destined for the Golgi apparatus or beyond are first packaged into small COPII-coated transport vesicles. These transport vesicles bud from specialized regions of the ER called ER exit sites, whose membrane lacks bound ribosomes. In most animal cells, ER exit sites seem to be randomly dispersed throughout the ER network.
Only Proteins That Are Properly Folded and Assembled Can Leave the ER
To exit from the ER, proteins must be properly folded and, if they are subunits of multimeric protein complexes, they may need to be completely assembled. Those that are misfolded or incompletely assembled are retained in the ER, where they are bound to chaperone proteins, such as BiP or calnexin. The chaperones may cover up the exit signals or somehow anchor the proteins in the ER. Such failed proteins are eventually transported back into the cytosol where they are degraded by proteasomes. This quality-control step is important, as misfolded or misassembled proteins could potentially interfere with the functions of normal proteins if they were transported onward. The amount of corrective action is surprisingly large. More than 90% of the newly synthesized subunits of the T cell receptor and of the acetylcholine receptor , for example, are normally degraded in the cell without ever reaching the cell surface, where they function. Thus, cells must make a large excess of many protein molecules from which to select the few that fold and assemble properly.
The Retrieval Pathway to the ER with COPI-coated Transport Vesicles
COPI coats mediate the budding of vesicles that return to the ER from these clusters. The retrieval pathway for returning escaped proteins back to the ER depends on ER retrieval signals. Resident ER membrane proteins, for example, contain signals that bind directly to COPI coats and are thus packaged into COPI-coated transport vesicles for retrograde delivery to the ER. Unlike the COPII-coated vesicles that bud from the ER, these vesicles carry back to the ER resident proteins that have escaped, as well as proteins that participated in the ER budding reaction and are being returned. This retrieval process demonstrates the exquisite control mechanisms that regulate coat assembly reactions. The COPI coat assembly begins only seconds after the COPII coats have been shed. It remains a mystery how this switchover in coat assembly is controlled.
It synthesizes lipids, phospholipids, and steroids. Cells which secrete these products, such as those in thetestes, ovaries, and sebaceous glands have an abundance of smooth endoplasmic reticulum. It also carries out the metabolism of carbohydrates, detoxification of natural metabolism products and of alcohol and drugs, attachment of receptors on cell membrane proteins, and steroid metabolism. In muscle cells, it regulates calcium ion concentration. Smooth endoplasmic reticulum is found in a variety of cell types (both animal and plant), and it serves different functions in each. The smooth endoplasmic reticulum also contains the enzyme glucose-6-phosphatase, which converts glucose-6-phosphate to glucose, a step in gluconeogenesis. It is connected to the nuclear envelope and consists of tubules that are located near the cell periphery. These tubes sometimes branch forming a network that is reticular in appearance. In some cells, there are dilated areas like the sacs of rough endoplasmic reticulum. The network of smooth endoplasmic reticulum allows for an increased surface area to be devoted to the action or storage of key enzymes and the products of these enzymes.
(1) Lipid synthesis and lipid metabolism
Phospholipid and cholesterol synthesis are the important function of sER. The enzyme needed in synthesizing phospholipid faces to the cytoplasmic side of ER membrane, so the new synthetic phospholipid can only inlay the cytoplasmic side of ER membrane initially, and then, with the help of flippase, a part of new phospholipid flips from the cytoplasmic side of ER membrane to the lumen surface of it, by which makes the phospholipid bilayer of ER membrane stretch parallel.
sER has the entire enzyme system that can synthesize cholesterol and transform it into steroid hormone.
(2) Glycogen Metabolism
(3) Detoxifcation
The detoxifcation of hepatopcyte counts on sER. There is an important oxidase system on sER of hepatopcyte, and it can deteriorate exogenetic and endogenic poison or medicine, or it can change them to something easy-egested and then egests them.
(4) Muscle Contraction
In skeletal muscle cell, sER transform into sarcoplasmic reticulum. Sarcoplasmic reticulum on which Ca2+-ATP enzyme are distributed, regulates the shrink and laxation of muscle respectively by pumping Ca2+ out and in. When muscle is relaxing, Ca2+-ATP enzyme pumps Ca2+ into sarcoplasmic reticulum lumen. When nerve is impulsing, sarcoplasmic reticulum releases a multitude of Ca2+ to cytoplasm. Meanwhile, Ca2+ activates ATP enzyme to break down, and the energy released from this process will be used for muscle contraction.
ER is a kind of sensitive organelle, and many deleterious factors can lead to pathological changes, such as oxygen deficiency, radiation, infection, hunger and chemical.
The Golgi apparatus is an organelle found in most eukaryotic cells. The Golgi apparatus packages proteins into membrane-bound vesicles inside the cell before the vesicles are sent to their destination. The Golgi apparatus resides at the intersection of the secretory, lysosomal, and endocytic pathways. It is of particular importance in processing proteins for secretion, containing a set of glycosylation enzymes that attach various sugar monomers to proteins as the proteins move through the apparatus.
Because of its large and regular structure, the Golgi apparatus was one of the first organelles described by early light microscopists. It consists of a collection of flattened, membrane-enclosed cisternae, somewhat resembling a stack of pancakes. Each of these Golgi stacks usually consists of four to six cisternae, although some unicellular flagellates can have up to 60.
Each Golgi stack has two distinct faces: a cis face (or entry face) and a trans face (or exit face). Both cis and trans faces are closely associated with special compartments, each composed of a network of interconnected tubular and cisternal structures: the cis Golgi network (CGN) (also called the intermediate compartment) and the trans Golgi network (TGN), respectively. Proteins and lipids enter the cis Golgi network in vesicular tubular clusters arriving from the ER and exit from the trans Golgi network bound for the cell surface or another compartment. Both networks are thought to be important for protein sorting. As we have seen, proteins entering the CGN can either move onward in the Golgi apparatus or be returned to the ER. Similarly, proteins exiting from the TGN can either move onward and be sorted according to whether they are destined for lysosomes, secretory vesicles, or the cell surface, or be returned to an earlier compartment.
The Golgi apparatus is especially prominent in cells that are specialized for secretion, such as the goblet cells of the intestinal epithelium, which secrete large amounts of polysaccharide-rich mucus into the gut (Figure 13-24). In such cells, unusually large vesicles are found on the trans side of the Golgi apparatus, which faces the plasma membranedomain where secretion occurs.
Proteins exported from the ER enter the first of the Golgi processing compartments (the cis Golgi compartment), after having passed through the cis Golgi network. They then move to the next compartment (the medial compartment, consisting of the central cisternae of the stack) and finally to the trans compartment, where glycosylation is completed. The lumen of the trans compartment is thought to be continuous with the trans Golgi network, where proteins are segregated into different transport packages and dispatched to their final destinations-the plasma membrane, lysosomes, or secretory vesicles.
In summary, the composition of Golgi complex is:
① Cis golgi network(CGN)
Cis golgi network closes to endoplasmic reticulum (ER). Its function is mainly to identify the glycoprotein and lipid that from endoplasmic reticulum (ER). After the recognition, most glycoprotein and lipid shift to medial Golgi stack, and those retention proteins that carry with ER retention signal are retrieval transported to endoplasmic reticulum (ER).
② Medial Golgi Stack
Medial golgi stack locates between cis Golgi network and trans Golgi network. Its functions are mainly to glycosylation modify for glycoprotein O-linked oligosaccharides, elaborate and synthesize glycolipid, etc.
③ Trans Golgi Network (TGN)
Trans golgi network face to membrane, its function is to select, package and directed transport proteins.
Golgi complex is made up of about 60% proteins and about 40% lipids. Of all kinds of enzymes enriched in Golgi, glycosyltransferase is the characteristic enzyme which can transfer oligosaccharide to protein to generate glycoprotein.
Protein sorting occur in both cis Golgi network (CGN)and trans Golgi network (CGN)
Proteins from the ER are transported to the Golgi apparatus at the cis Golgi network. Proteins entering the CGN can be sorted, either moving onward in the Golgi apparatus or being returned to the ER; Proteins are sorted in the trans Golgi network and transported in vesicles to their final destinations. In the absence of specific targeting signals, proteins are carried to (1) the plasma membrane by constitutive secretion. Alternatively, proteins can be diverted from the constitutive secretion pathway and targeted to other destinations, such as (2) lysosomes or (3) regulated vesicle secretion from the cells.
Oligosaccharide Chains Are Processed in the Golgi Apparatus
As described in the ER section, a single species of N -linked oligosaccharide is attached en bloc to many proteins in the ER and then trimmed while the protein is still in the ER. Further modifications and additions occur in the Golgi apparatus, depending on the protein. The outcome is that two broad classes of N-linked oligosaccharides, the complex oligosaccharides and the high-mannose oligosaccharides, are found attached to mammalian glycoproteins. Sometimes both types are attached (in different places) to the same polypeptide chain.
Proteoglycans Are Assembled in the Golgi Apparatus
It is not only the N-linked oligosaccharide chains on proteins that are altered as the proteins pass through the Golgi cisternae en route from the ER to their final destinations; many proteins are also modified in other ways. Some proteins have sugars added to the OH groups of selected serine or threonine side chains. This O -linked glycosylation, like the extension of N-linked oligosaccharide chains, is catalyzed by a series of glycosyl transferase enzymes that use the sugar nucleotides in the lumen of the Golgi apparatus to add sugar residues to a protein one at a time. Usually, N-acetylgalactosamine is added first, followed by a variable number of additional sugar residues, ranging from just a few to 10 or more.
In summary, both N -linked glycosylation and O -linked glycosylation occur in Golgi apparatus.
Hypertrophy: this symptom is commonly seen in patients with hyperfunction (cell secretion increase) and compensated hyperfunction (neighboring cells dysfunction).
Atrophy: this symptom is commonly seen in patients with toxicosis.
Golgi complex has the functions of transporting and secreting lipid and lipoprotein. Lipoprotein particle can be seen in hepatocyte. When fatty liver or carbon tetrachloride poisons, the contents of golgi complex in fatty liver change and lipoprotein particle disappear. They are replaced by a lot of outstretched or fractured vesicles in which full of lipidosome.
(3) Changes of Golgi complex in cancer cell
The lower differentiation of cancer cells is, the less flourish of golgi complexes is. This shows that cells secrete lowly, and cancer cells now are concentrated on growing and reproducing, and concentrated on synthesizing of proteins as well. Therefore, the grade malignancy of cancer cells is higher.
Lysosomes are membrane-enclosed organelles that contain an array of enzymes capable of breaking down all types of biological polymers-proteins, nucleic acids, carbohydrates, and lipids. Lysosomes function as the digestive system of the cell, serving both to degrade material taken up from outside the cell and to digest obsolete components of the cell itself.
(1) Membrane:
① The lysosome maintains its acidic condition by pumping in protons (H+ ions)from the cytosol across the membrane via proton pumps. Vacuolar H+-ATPases are responsible for transport of protons. In this way a steady acidic environment is maintained. ②The membrane protein of lysosome was highly glycosylated and negatively charged, thus protecting membrane from hydrolysis of hydrolase.
(2) Enzyme: There are more than sixty kinds of acid hydrolases in lysosome. There are different kinds and number of enzymes in lysomes from different types of cells. Phosphatase is the maker enzyme of lysosome.
According to the formation and function, lysosome can be classified to endolysosome and phagolysosome. Transport vesicle and endosome merged into endolysosome; Phagolysosome was formed by the fusion of endolysosome and phagocytosed substrates.
① Hydrolase (zymoprotein )of lysosome is synthesized at ribosome on rER.
② Zymoprotein is partially galactosylated in rER and then is transported to cis-face of Golgi complex.
③ Sorting signal Ｍ-6-P is added to zymoprotein, and specifically binds with Ｍ-6-P receptor in trans-face of Golgi complex, forming clathrin-coated transport vesicles in the way of budding.
④ These clathrin coated transport vesicles budded from Golgi complex, dropping off clathrin coat and becoming smooth transport vesicle.
⑥These transport vesicle and endosome formed from endocytosis merged into endolysosome
⑦ When PH of endolysosome becomes down to about 6 because of proton pump on the membrane pumping H＋ into endosome, Ｍ-6-P breaks up with it receptor, Ｍ-6-P receptor returns to Golgi complex in the way of budding transport vesicle.
Phagolysosome is divided to autophagolysosome and heterophagolysosome according to the origin of zymolyte.
① Autophagolysosome
Zymolyte of autophagolysosome is endogenous，including aging or damaged organelles ( mitochondria, endoplasmic reticulum) and cell contents (glycogen，lipid).
② Heterophagolysosome
Zymolyte of heterophagolysome is exogenous endocytotic or phagocytosed substrates, such as aging cells, cell debris and macromolecular substance. Heterophagolysosome is commonly seen in mononucleate-macrophage system, leukocyte, hepatocyte, nephrocyte and so on. It plays a vital role in defensive system.
Residual body
In the final digestion stage of heterophagolysome, due to the decreased activity of hydrolytic enzyme, some undigested substrates remain and become residual body. Residual body can accumulate in aging cells, such as brain cells, myocardial cells and hypatocyte.
Lysosomes contain a variety of enzymes, enabling the cell to break down various biomolecules it engulfs, including peptides, nucleic acids,carbohydrates, and lipids. The enzymes responsible for this hydrolysis require an acidic environment for optimal activity.
In addition to being able to break down polymers, lysosomes are capable of fusing with other organelles & digesting large structures or cellular debris; through cooperation with phagosomes, they are able to conduct autophagy, clearing out damaged structures. Similarly, they are able to break-down virus particles or bacteria in phagocytosis of macrophages.
(1) Autophagy
Autophagy is a process that lysosome digests endogenous article. Lysosome can clean the aging and damaged organelles, and also it makes sure a steady internal milieu in cell and the update of organelle.
When in staress state, autophagy of cell strengthens. For example, in those cells that are starving, damaged or dying, a large number of autophagic vacuole appears, which can be regarded as self-protection measure. Cell digests a part of it so as to maintain the whole cells life.
(2) Heterophagy
Heterophagy is a process that lysosome digests exogenous article. For example, macrophage digests and dissolves cell's fragment, bacteria and virosome that are phagocytized, supplies nutrient substance for cell's living and makes up cell structure, so it does play a significant role in cell defence.
Human is invaded and attacked by many kinds of microorganisms everyday. As invasion effect overcomes heterophagy, human will be ill. Some causative agent(mycobacterium leprae and mycobacterium tuberculosis)can resist the digestive function of macrophage and breed in devouring bubble, and at the same time it can also escape from digestion function by stopping lysosomes and phagocyte from integrating.
(3) Autolysis
Autolysis is a process that isophagay happens to cell resulting from the rupture of membrane of lysosome and the spillover enzyme of lysosome. For instance, in human embryonic period, his fingers and toes divides; endometrium of mammal shrivels periodically, that is catamenia.
When in inflammation, cell autolysis is good for eliminating infected tissue and necrosing, facilitating new tissue to grow. In initial period of process of sore coming into being, a lot of bacteria are attacking. And then macrophage gathers around lesion under the dive function. After macrophage overworks, lysosome releases lots of bacterolysin to kill bacteria. Meanwhile, macrophage suicides. Thus, sanies is composed by dead macrophage.
(4) Phagolysis
Phagolysis is a process that enzyme of lysosome is released outside cells by exocytosis.
① Assisting sperm and ovum in fertilizing
Actually, acrosome of sperm is a specialized lysosome, including various types of hydrolytic enzyme, such as, acrosin. During fertilization, after sperm and ovum meet, recognize and contact, the membrane of both acrosome and cell membrane integrate to be a pore canal that makes hydrolytic enzyme in acrosome liberate. Then the free hydrolytic enzyme digests the transparency zone and makes it to be a hole so as to opening a path for sperm nucleus to enter ovum, by digesting follicular cells surrounding ovum and membrane of ovum. After fertilization, zygote generates a kind of article that is able to inhibit acrosome and blockades channel for forbidding other sperm entering ovum.
② Updating Sclerotin
During the process of the birth and and rebirth of bone, osteoblast produces new sclerotin while osteoclast destroys the timeworn one. Lysosome in osteobalst can be released outside cells, absorbs and eliminates timeworn sclerotin, which is an important procedure of sclerotin update.
(1) Disease results from lysosomal enzyme deficiency
Owing to the congenital shortage of some kinds of enzyme in lysosome, the relevant substrate can not be dissolved so that it accumulates in lysosome, which causes overloading. Then, deposition disease comes into being.
① Glycogenosis
Due to α-glucosacchaarase deficiency, glycogen metaboly is blocked so it accumulates in many kinds of tissue in body, damaging cerebralis, liver, kidney, adrenal gland, skeletal muscle and cardiac muscle, etc. In the end, lysosome cracks to leak enzyme, to badly destroy tissues and cells.
② Tay-Sachs Diesease
It can be called amaurotic idiocy. Lysosome lacks aminohexose esterase A so that nerve ganglion accumulates a lot in cerebralis, nerve system, heart and liver. Its clinical manifestation is to be blind gradually, till anoia and paralysis.
③ Mucopolysaccharidosis
Mucopolysaccharide is kind of glycoproteins. It maintains the elasticity of human skin and connective tissue, so it prompts metaboly because of the easy elasticity deficiency. Owing to the shortage of digestive enzyme, mucopolysaccharide gets obstruction in metabolizing, and it will deposit in many kinds of tissue, causing crude face, nubecula, anchylosis, hepatosplenomegaly and mental retardation, etc.
There is an assumption that deleted enzyme in lysosome is packaged in artificial lipid, then lipidosome combines with lysosome after cytophagy. Meanwhile, enzyme in lipidosome enters lysosome for therapeutic purposes.
(2) Disease results from lysosome leaking
① Silicosis
Silicosis is occupational disease for those who contacts dust or works in mine. After a silica particular in air is inhaled to lung, it arrives at alveolar space and is swallowed by macrophage, then phagosome, which will integrate lysosome. Lysosome can only partly break down SiO2 to be silicic acid molecule which can integrate lysosomal membrane and cause lysosomal membrane to break, and then lysosomal enzyme and SiO2 are leaking while macrophage autolyzes. Next, SiO2 is swallowed by macrophage again. The process continues to repeat. Lots of dead macrophage releases macrophage fibration factor to rotate fibrocyte to secrete numerous collagen material that accumulates in lung. Finally, fibration and declining elasticity of lungs leads to silicosis.
② Gout
Patient who suffers from gout has a high level urate in his body fluid. Urate deposits in clearance of connective tissue (joint cartilage tissue) to form crystal. These urate crystals can be swallowed by hemameba and combine with lysosome. Urate crystal breaks lysosomal membrane and makes it leak. After hemameba autolyzes, it erodes the tissue that it deposits in, giving rise to the reaction of acute inflammation.
③ Rheumatoid arthritis
The brittleness of lysosomal membrane is increasing, and lysosomal enzyme partly becomes free, during which collagen enzyme erodes joint cartilage, causing part joint injure, that is, rheumatoid arthritis. Its lysosomal enzyme being released may result from that some kinds of rheumatoid are swallowed by macrophage and hemameba then lysosomal enzyme is activated.
Peroxisomes (also called microbodies) are organelles found in virtually all eukaryotic cells. They are involved in catabolism of hydrogen peroxide.
Peroxisome is a kind of circular or oval globule surrounded by one layer unit membrane, having lattice structures of high electronic density in in the center, urate oxidase crystalline core, called nucleoid. Peroxisome and lysosome are very similar in shape, so they can be distinguished only from the nature of enzymes.
Peroxisome contains more than forty kinds of enzymes, mainly including oxidative enzyme, catalase and peroxidase. Of them, catalase existing in all peroxisomes is the marker enzyme of peroxisome.
1. Oxidative enzyme is able to oxidate organic substrates（RH2）and remove the hydrogen atoms off organic substrates. At the same time, it can revert deoxidized oxygen into hydrogen peroxide（H2O2）.
oxidase
RH2＋O2——-→R＋H2O2
2. Catalase is able to revert the hydrogen peroxide (H2O2) into water (H2O), preventing the H2O2 from accumulating in the cells, and eliminating or reducing the toxicity of H2O2 to cells.
catalase
RH2＋H2O2———→R＇＋2 H2O
(1) Detoxication
Catalase can utilize hydrogen peroxide to oxidate substrates, such as methanol, ethanol, formic acid, formaldehyde, et al. The oxidation can turn these toxic substances into innocuous substance, and deoxidize H2O2 into H2O. This kind of detoxication is absolutely crucial to liver and kidney. For example, if someone drinks ethanol, almost half of it will be oxidized to ethanol by peroxisome, relieving toxicity of ethanol to cells.
catalase
RH2＋H2O2———→R＋2 H2O
(2) Oxygen regulation
20% of oxygen in cells is consumed by peroxisomes, and the rest 80% is provided for mitochondria.
When oxygen concentration increases, the oxidation ability of mitochondria cannot increase accordingly, but peroxisome can. Therefore, when the high concentration of oxygen occurs, peroxisome can regulate oxygen concentration, avoiding damage of high oxygen concentration to cells.
oxidase
RH2＋O2——-→R＋H2O2
(3) metabolism of nucleic acid, fat and glucose
1. Hereditary acatalasemia
Lack of catalases and reduction of anti-infection ability can easily lead to diseases, like stomatitis.
2. Pathologic change
When people suffer from hyperthyroidism, chronic alcoholism or chronic hypoxidosis, the number of peroxisomes in the hepatocyte increases; when hypothyroidism, hepatic steatosis or hyperlipemia occurs, the number of peroxisomes decreases.
Since 2021-09-29, 3769 persons visited this page till now.