Structural Biochemistry/Cell Organelles

General Information

Pictorial representation of organelles in a typical animal cell

Cell

Structural biochemistry plays a vital role in the functions of an organism's cell through various means, one of them being the organelles in a cell. It is through the structure and functions of living molecules (and some non-living), such as nucleic acids, amino acids, purine, and lipids that life is even possible.

Organelles are the components of the cell that synthesize new materials, recycle old materials, transport molecules, and anything else that is essential to ensure the proper survival of the cell and its propogation. Organelles incorporate all broad ranges of organic molecules including nucleic acids, amino acids, carbohydrates, and lipids to produce a viable cell.

Cellular Organization of the Membrane

As discussed before, the "lipid bilayer" that forms the cell membrane contains membrane protein and cholesterol. The membrane protein plays a vital role in the membrane functions while the cholesterol performs the structural role within the membrane.

There are two types of protein membranes:

• Integral membrane protein: lies within the membrane
• Peripheral membrane protein: bound to membrane

The cell membrane is often referred to as a mosaic. Proteins in the membrane determine most of the membranes specific function. These proteins are categorized as integral and peripheral proteins. Integral proteins can perform a number of functions such as being transport proteins that provide a hydrophilic channel across the membrane. Integral proteins can also act a receptor sites for chemical messengers like hormones. Enzymes can also be found in the lipid bilayer with its active site exposed to substances in adjacent solutions. Elements of the cytoskeleton may also be bonded to the membrane proteins; a function that helps maintain cell structure. The structure of these membrane protein can also be either alpha helices or beta sheets. Due to the hydrophobic interactions, the hydrophobic residues of the alpha helices will not exposed to the aqueous environment. The beta sheet forms a hollow cylindrical configuration where the inside is hydrophilic. The cylindrical structure is driven by the unsatisfied hydrogen bonding at the ends of the beta sheet. Wrapping around itself, the beta sheet is able to satisfy all hydrogen bonding.

Cholesterol regulates the fluidity of the membrane in eukaryotic cells. The ability to incorporate cholesterol into the cell membrane with hydrophobic and hydrophilic interactions allows the cholesterol to disrupt the phospholipid interaction within the bi-layer. Since prokaryotic cells do not have cholesterol to regulate fluidity, these cells depend on the variation in the saturation level and length of the fatty acid chain. The shorter and more saturated the chain the more rigid the membrane will become (due to the fact that the longer and saturated chains can interact more closely with one another)

Fluid Mosaic Model

This claims that the lipid layer plays a dual role in cell membrane. The cell membrane serves as the solvent for the integral membrane proteins, and it also serves as a barrier that separates the cellular activities within the cell from the extracellular space. The permeable barrier regulates what enters the cell. This fluid mosaic model is regulated by the concentration of cholesterol and fatty acid chain mentioned above.

The Properties of Membrane

• Sheet-like structure
• Formed by lipids and proteins
  • The different ratio of lipids to proteins will correspond to the different cell types and organelles
• Lipid
  • Which gives it the amphiphatic properties
• Non-covalent assemblies
  • That includes: van deer Waals, hydrogen bonding, and hydrophobic interactions
• Asymmetric
  • The orientation of the proteins are fixed and will not interchange between the inner or outer layers
• Fluid Structures
• Electrically polarized
  • This is due to the charged head groups

Common Organelles

Ribosome

Ribosomes are the sites by which nucleic acids are translated and proteins are synthesized. Ribosomes are about 20 nm in diameter and are composed of ribosomal RNA and proteins. They can be found freely floating in the cytosol and not attached to any organelles in prokaryote cells. In eukaryote, ribosomes may be found on the rough endoplasmic reticulum. The rough ER earns its name because of ribosomes on its surface, giving a studding appearance. The proteins produced by the ribosomes of the rough ER are sent through the lumen of the ER, where they are modified. The protein is then transported in a vesicle to the Golgi Apparatus, where the protein undergoes further modification.

First, the genetic code from DNA is transcribed into a complementary strand called messenger RNA (mRNA) by DNA polymerase. In prokaryotes, the mRNA moves away from the nucleoid and is bound to free-floating ribosomes in the cytosol. Whereas, in eukaryotes, mRNA is made in the nucleus and transported across the nuclear membrane and into the cytoplasm. This is called translocation. In the next step, known as translation, the mRNA is attached to the ribosome, and codons on the mRNA are matched with the complementary nucleotide bases (anticodons) located on a transfer RNA (tRNA) molecule. The enzyme aminoacyl tRNA synthetase matches the tRNA codons with the appropriate amino acids through a series of esterification reactions. Ribosomal RNA synthesizes the protein through use of RNA polymerase. This elongates the protein until a stop codon terminates the protein synthesis chain. The synthesis of proteins always moves in the direction of the N-terminus to the C-terminus. Prokaryotic ribosomes typically produce ribosomes at a much faster rate than eukaryotic ribosomes.

Cell Membrane

The cellmembrane, as explained above, is a selectively permeable barrier of ions and molecules that move into and out of the cell.

Organelles Exclusively Found in Prokaryotes

Prokaryotes typically have no compartmentalized organelles. The cell's DNA and ribosomes are free-floating with the cytosol, which is surrounded by a cell membrane. A prokaryotic cell is generally one hundred times smaller than an eukaryotic cell.

Nucleoid

While lacking a nucleus, the nucleoid in prokaryotes is the region in which DNA is tightly packed in a supercoil without a membrane. This region also consists of a much smaller content of RNA and protein, which are typically from messenger RNA and the proteins holding the supercoil of the DNA together.

Pili

Prokaryotes use their pili to transfer gene and attaching to surface of microorganisms. Bacteria cells can attach to multiple of acceptor bacteria cells at once(this process is called conjugation), which give prokaryotes the ability to become resistant to drug--adapt to a new environment--with more ease.

Organelles Exclusively Found in Eukaryotes

Eukaryotes, which include animals, plants, fungi, and protists, are typically more complex than prokaryotic cells. There are many compartmentalized organelles enclosed in membranes within the cell which allow for various reactions to take place. The eukaryotic cell is typically much larger than the prokaryotic cell, usually by a factor of around 100.

Nucleus

The nucleus is one of the primary organelles that distinguish eukaryotic cells from prokaryotic cells. The nucleus of eukaryotic cells contain Chromosomes that house the genes coding for the synthesis of proteins, antibodies and molecules that perform the basic functions of the cell. The genome is surrounded by a nuclear envolope to ensure that its genetic material is isolated from other organelles, the cytoplasm and other chemical reactions. Replication, transcription and RNA processessing (such as the cap at the 5' end and a poly-A tail at the 3' end RNA splicing) occur in the nucleus,while translation occurs seperately in the cytoplasm. Prokaryotes in the other hand localize their genome within the cell without a nuclear envolope to seperate it from the cystoplasm. Thus, replication, transcription, translation and all other chemical reactions all occur in the same location

• Chromosomes

Chromosomes consist of proteins and DNA that are tightly bound together. These condensed structures of DNA house the genes of the cells coding for expression of the cell's different proteins and structures. In most prokaryotes these chromosomes are circular whereas those of eukaryotes are linear. In eukaryotes the chromosomes are tightly packed into chromatins which vary in structure between different eukaryotic cells. These chromatin structures consist of a centromere and chromatids. The ends of the chromosomes are termed telomeres.

• Telomeres

Telomeres are defined as the sequence of DNA that occurs at the end of the chromosomes. These parts of the DNA strand contain hundreds of repeats of a six-nucleotide sequence (These repeats are usually rich in the guanosine nucleotide). It was found that one strand containing the repeats, was longer than the other. Thus these elongated sequences formed duplex loops which are stabilized by telomere binding proteins. The reason for this is to protect the rest of the chromosome from degradation.

• Telomerase

Telomeres are sequenced by special proteins (a type of polymerase) called telomerase. Normal DNA/RNA polyermase have the problem of only being able to synthesize the sequence from the 5'-->3' direction. So after the primer is removed the strand would be shortened by one nucleotide. Most telomeres are concentrated in guanine residues, and often times these guanine residues will normally pair with cytosine residues. The guanine sometimes pair with themselves (through hydrogen bonds), forming loops.

The telomerase is able to add the loops of telomeres because it contains an RNA molecule that acts as a small template. Along with this RNA molecule, telomerase also contains a protein related to an enzyme (found in the retrovirus) that copies RNA to DNA. So Telomerase is also a specialized reverse transcriptase.

Nucleolus

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Endoplasmic Reticulum

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Mitochondrion

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Golgi Apparatus

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Centriole

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Cell Wall

The cell wall, located outside the cell membrane, is a tough layer that provides the rest of the cell with structure support and protection. Cell walls are present in plants, fungi, algae, some archaea, and bacteria cells, but not in animal cells. The cell wall in plant cells is composed of cellulose, while it is composed of peptidoglycan in bacteria cells.

Chloroplasts (plants)

Chloroplasts, found in plant and algae eukaryotes, are the sites of photosynthesis. Here, plant cells absorb light energy and undergo reactions involving water and carbon dioxide to produce sugars (such as glucose), which serve as the chemical energy for other plant processes. This energy is harnessed in the form of adenosine triphosphate (ATP).

Chloroplasts are typically found within the mesophyll cells, or the inner tissues of a leaf. Chloroplasts are discs that are typically somewhere between 2-7 micrometers in diameter and 1 micrometer thick. Chlorophyll, which is the green pigment located within chloroplasts, give plants their typical green color. During photosynthesis, carbon dioxide enters the leaf through microscopic pores known as the stomata, and oxygen leaves as a biproduct through the stomata. The dense fluid found within the chloroplast is known as the stroma, and amongst this are several membranous sacs shaped in flat discs with their own compartments, known as the thylakoids. The thylakoids are arranged in a stacked conformation known as the grana. The space within these compartments are called the thylakoid space. The membranes of the thylakoid hold the cell's chlorophyll.

Vacuole

Vacuoles serve as the cell's storage centers of food and other necessary materials. The vacuole further functions in the removal of unwanted structural materials, the containing of several waste products and small molecules (which could involve the isolation of potentially harmful products in the cell), the exportation of unwanted materials from the cell, and the maintenance of an acidic internal pH and constant internal pressure.

In plants, the central vacuole is typically the largest compartment of all the cell's organelles, occupying in itself the majority of the cell volume. This large compartment is enclosed by a membrane called the tonoplast, which is selectively permeable to certain solutes within the cytosol. The solution inside the vacuole is referred to as cell sap, which is of different composition from the cytosol. Some plant vacuoles contain pigments that color the cells, such as during pollination season by which the plant must attract different organisms to carry out its fertilization. Plants maintain its structure through the maintenance of internal pressure through the manipulation of water into and out of the vacuole. Through water osmosis, water diffuses into the vacuole, which places pressure onto the cell wall. If too much water were to be lost, this pressure against the cell wall would be lacking, and the cell would collapse onto itself. Thus, cells also serve to maintain the cell's size. Another important feature of the vacuole in plants is that an enlarged central vacuole may add a specific amount of pressure against the other compartments in the cell and push them towards the cell membrane, thereby giving a type of conformation that permits the absorbance of more solar energy.

Vacuoles in animal cells serve mostly as the receptacles of waste products and materials from phagocytosis.

Lysosome

The lysosome is a membranous sac ofenzymes that an organism utilizes in the digestion of macromolecules. The enzymes found within lysosomes are hydrolytic, meaning that during reaction a single water molecules is slit up into the hydrogen and hydroxide ions. This type of reaction is typically suited for the break down of polymers with an acid as a catalyst. It is from this reaction that lysosomes achieve their name because to "lyse" means to break a molecule into two compounds. Lysosomes work optimally best under acidic conditions and lose their potency if its contents leak into the cytosol, as the pH of the cytosol is rather neutral. Furthermore, excess leakage of lysosomic contents may cause autodigestion of the cell.

The most important types of lysosomal enzymes are as listed:

• Lipase: water-soluble enzymes involved in the catalysis of the hydrolysis reaction (by which a water molecule is broken) that break the ester bonds which hold lipids together. This enzyme is present in almost all living organisms.
• Carbohydrase: the enzymes which hydrolyze polysaccharides into disaccharides. Some common carbohydrases are sucrase (which hydrolyzes sugars), lactase (which hydrolyzes lactose), and amylase (which hydrolyzes starches).
• Nuclease: the enzymes that break the phosphodiester bonds that hold nucleotides together in nucleic acids. This type of enzyme is vital in the study of DNA.
• Protease: the enzymes that hydrolyze the peptide bonds in proteins. This enzyme is present in all living organisms.

Through use of the aforementioned types of enzymes, lysosomes are responsible for intracellular digestion. In the process of phagocytosis, digestion products, such as simple sugars and amino acids, are passed into the cell's cytosol and serve as the nutrients for further reactions performed by other cell compartments. Lysosomes may also use this process is the recycling of the cell's own organic materials during autophagy. During this process, a small amount of cytosol or damaged organelle is surrounded by a membrane that the lysosome fuses to. This becomes broken down by lysosomal enzymes.

In lysosomal diseases, the lysosome lacks a functioning enzyme, causing imbalance in the cell. In Tay-Sachs Disease, for example, a lipase is in malfunction or missing, and the brain malfunctions due to over-accumulation of lipids in the cells.

Peroxisome

Peroxisomes are the centers by which the cell may be rid of potential toxins. The peroxisome is in itself a receptacle of oxidative enzymes that remove hydrogen atoms from certain organic substances to produce peroxides, which in itself is harmful. This peroxide serves to oxidate the potentially harmful substances, such as alcohol. In reaction, a hydrogen leaves the peroxide compound, and the result is the R group of the reactant compound in question and molecules of water.

Cell Compartmentalization

Evolution

During evolution, cells start to develop two compartments, the outer and inner aqueous compartment. The advantage of having an inner aqueous compartment allows the better segregation of cellular organelles from the external environment. Thus, each organelle is able to develop and refine its structural and functional distinction inside this aqueous compartment throughout the course of evolution. The "lipid bilayer" (further discussed) existed as a protective wall that allow hydrophilic interaction in the external and internal compartment of the cells while maintain proficient rigidity with its hydrophobic interior structure. The inner aqueous compartment ultimately becomes the cytoplasm which serves the same purpose as it has been during evolution.

Liposomes

Liposomes are essentially lipid vesicles surrounded by a circular phospholipid bilayer. They form identical structure as other phospholipids vesicles: interior hydrophobic tails away from the aqueous solution, and external hydrophilic heads towards the aqueous solution. Liposomes are formed through the process called sonification, which results in ions and solutes inside the enclosed compartments. They can be used to study the permeability of certain membranes and transportation of ions or solutes found in different cells.

Lipid Bilayer

Lipid bilayers form in a spontaneous and self-assembled manner in aqueous environment. Its unique properties allow the formation of enclosed compartments. The sheet-like bimolecular structure called lipid bilayers or energetically favored because of the hydrophobic interactions. As mentioned previously, phospholipids, an amphiphlic moiety as a major class of membrane lipids, exist in an aqueous solution. The hydrophobic tails from two phospholipid bilayers interact with each other to form a hydrophobic center. Meanwhile, the hydrophilic heads line up with each other, form a hydrophilic coating on each side of the bilayer, and isolate the inner compartment from the outer environment.

• Summary of Major Forces
  • Hydrophobic Interactions: the major driving force
  • Van der Waals Interactions: hold the hydrophobic tails together
  • Hydrogen Bonding: bind the hydrophilic heads with water, help stabilize the lipid bilayer structure.

Membrane Motion

Lateral Diffusion

The lateral diffusion, or the motion of moving laterally, of the biological membranes illustrates the fact that the membranes are not rigid and static. The technique known as Fluorescence Recovery After Photobleaching (FRAP)assists to visualize the lateral diffusion of membrane proteins.

• Experimental Procedures
  • Label a specific cell component with fluorescence.
  • Use a intense beam of laser light to bleach, or destroy, the small part of the florescence labeled cell surface.
  • The intensity of bleaching recovers as the lateral diffusion of unbleached membrane proteins move into the region that has been bleached.

Transverse Diffusion

Transverse Diffusion describes the movement of molecules from one side the membrane to the opposite. In comparison to the rapid movement of lateral diffusion, the speed of transverse diffusion (flip-flop) is rather slow. The reason for the preservation of membrane structural asymmetry is due to the greater energy barriers formed in order to travel across membrane from one side to the other.

The Cycling Process of Cells

Three types of cell division: binary fision (in prokaryotes), mitosis and meiosis (in eukaryotes).

Cells Division

Cell division is a process that a cell gets divided and then duplicated. In prokaryotes, cells are divided by binary fission. In eukaryotes, the process becomes more complicated that there are three steps or periods for division. The cell grows during the period of inter-phase, when it absorb nutrients for mitosis and duplication of DNA. Then the cells comes to mitosis phase. During this period, the cell will split into two different daughter cells. Moreover, the chromosomes in its nucleus will also be divided into two equivalent parts, each into separate nuclei. Finally, the cell finishes division during cytokinesis.

Cells Aging

It has been a convention now that aging is due to continuous damage to various molecules in our cells, including proteins, lipids and nucleic acids. There are internal and external reasons for the damage to happen.

The example for external reasons is oxygen, which is regarded as the necessity for human beings. However, when the oxygen absorbs only one or two electrons, making itself reactive, this kind of oxygen molecules will damage lipids, mutate genes, and destroy proteins, all leading to cellular injury.

Telomere

On the other hand, the internal reasons are related to cell retiring. According to the data, cells stop working when they divide about fifty times. This phenomenon might be traced to the period when a cell copies its chromosomes to its daughters. However, the very ends of the chromosomes will not be copied, so daughters’ chromosomes are shorter, compared to their maternal cell. Telomere, at the ends of cells’ chromosomes, supplies the genetic information, which is the same as that on the parts of maternal chromosomes left. Nonetheless, when a cell’s telomeres get shrunk to a minimum size, the cell will stop dividing and lose its function. The picture to the right shows the telomeres in 46 human chromosomes. People might ask what the use of cells is to become retired and why not keep telomerase active to span our life. However, cancer cells might make use of telomerase to reactivate the cells, which would be divided to cancer cells in the end.

Moreover, DNA mutations can also lead to cellular injury. One of the examples is a kind of disease, called “Werner Syndrome”. The mutated gene in "Werner Syndrome" was found to controll an enzyme in DNA repairing process, which turned to be abnormal compared to normal people. Then this change caused excessive DNA mutations, finally accelerating aging.

Cells Death

There are two kinds of cell death: apoptosis and necrosis.

Apoptosis is programmed cell death that cells undergo self-destruction by regulation. At first, a cell shrinks and escapes from its neighbors. Later on, the surface of the cell breaks into fragments and also the nucleus then collapses. In the end, the whole cell dissembles. There will be some organelles cleaning up the remains. During apoptosis, unneeded cells or retired cells are eliminated efficiently without pain. Apoptosis plays a significant role in our body, which is self-destruction. When some cells in our body become infected, apoptosis can help eliminate them to avoid the virus spreading the whole body. However, viruses have several solutions to prevent apoptosis, such as stop cells’ suicide by confusing them with a similar “off” signal as that sent by apoptosis. Therefore, further research in apoptosis can promote the development of clinical medicine.

Necrosis is unplanned cell death. It happens when the outer membrane of a cell is unable to control the liquid flowing across it. Then the cell shrinks and bursts. Finally, contents inside will flow out, blending into the tissues nearby. The reasons causing necrosis might be traumatic injury, infection, chemical poison, etc.

Balance in cells

Now we understand that some cells are created and some are killed. The truth is that these processes are designed well to keep our body healthy. The unbalance between apoptosis and mitosis, the two representatives in the cell cycling, might cause cancer, Parkinson’s, Alzheimer’s, etc.

Endocytosis

Endocytosis is the creation of internal membranes from the cell's plasma membrane lipid bilayer.This is a way for plasma membrane lipids and integral proteins to be brought inside the cell. It is thus the opposite of [exocytosis|exocytosis]. This allows cells to do things like regulate the sensitivity of cells to ligands since receptors can be removed from the cell surface by endocytosis. Plasma membrane buds, called caveolae, are on little creices on the surface of many mammalian cells. These can make up almost a third of a cells surface area. Given their structure, they are often involved in endocytic events. Another way of internalizing in cells is called phagocytosis. In this method, material can be take in when 'invaginations' are formed around particles to be engulfed while using or not using the growth of surrounding membrane extensions. (Doherty and McMahon)

References

1. Berg, Jeremy M. Biochemistry. 6th ed. W.H. Freeman, 2007.
2. Campbell, Neil A. Biology. 7th ed. San Francisco, 2005. 3. "Inside the Cell" of U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health National Institute of General Medical Sciences 4. "Mechanisms of Endocytosis". Doherty and McMahon, MRC Lab of Molecular Biology, Cambridge, UK.

5.Inside the Cell, U.S.DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health National Institute of General Medical Sciences 6. http://en.wikipedia.org/wiki/Cell_cycle 7. http://en.wikipedia.org/wiki/Mitosis 8. http://commons.wikimedia.org/wiki/File:Three_cell_growth_types.png 9. http://commons.wikimedia.org/wiki/File:Telomere.JPG