Structural Biochemistry/Cell Organelles

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.

Pictorial representation of organelles in a typical animal cell

Cell

Some properties of living organisms include high degree of chemical complexity and microscopic organization, systems to extract, transform and use energy from the environment, self-replication and self-assembly, sensing and responding to changes in the environment, define functions for each component and regulation among them, and history of evolutionary change.

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 propagation. Organelles incorporate all broad ranges of organic molecules including nucleic acids, amino acids, carbohydrates, and lipids to produce a viable cell.

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.

The major functions performed by proteins of the plasma membrane are:

1. Transport: Some membrane proteins provide selective hydrophilic channels for exchange of substances.
2. Enzymatic activity: Membrane proteins may also be enzymes with their active sites exposed to the surrounding solutions.
3. Signal transduction: Membrane proteins may act as receptors with specific binding sites that allows perfect fit with chemical messengers, which can cause the protein to change shape and allow it to relay the message to the inside of the cell.
4. Cell-cell recognition: Some glycoproteins allow specific identification by membrane protein of other cells.
5. Intercellular joining: Membrane proteins of adjacent cells may join together in different junctions.
6. Attachment to the cytoskeleton and extracellular matrix (ECM): Membrane proteins can be non-covalently bound with elements of the cytoskeleton in order to maintain cell shape and stabilize the location of certain membrane proteins.

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 model claims that the lipid layer has an important 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 lipid bilayers and proteins
• The different ratio of lipids to proteins will correspond to the different cell types and organelles which gives it the amphiphatic properties
• Non-covalent assemblies include 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 because of the charged head groups

Major Organelles

1. 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) (mRNA) by DNA polymerase. In prokaryotes, the mRNA moves away from the nucleoid and is bounded to free-floating ribosomes in the cytosol. However, 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. DNA replication also follows the 5' to 3' direction.

2. Cell Membrane

The cell membrane, as explained above, is a selectively permeable barrier of ions and molecules that move into and out of the cell. In other words, not all molecules are able to pass through the cell membrane. During the division of the cell, none of the membrane integrity is lost. As the cell grows, new lipid and protein molecules are placed into the cell’s plasma membrane.

Prokaryotes Organelles

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 a eukaryotic cell.

1. Nucleoid

In the nucleoid, the chromosomal DNA is wrapped around binding proteins. "Replication by DNA polymerase and transcription by RNA polymerase occur at the same time within the nucleoid."

2. Pili

Pili (Fimbriae)is a thin structure that stick out from the surface. They are made out of a single protein called pilin. Pili's functions include DNA transfer, binding to surfaces, and motility. Pili has the ability to attach to a substrate. One type of pili called sex pili, it attaches a "male" donor cell to a "female" recipient cell for transfer of DNA. This process is called conjugation.

Eukaryotes Organelles

Eukaryotes include animals, plants, fungi, and protists. They 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. Each organelle in Eukaryotes has their own function in the cell.

1. Nucleus

The nucleus is one of the primary organelles that distinguish eukaryotic cells from prokaryotic cells. It is an organelle that enclosed compartment with a specific function. It contains chromatin. Nuclei contains nucleolus (where ribosome assembly is). Ribosomal RNA get together with ribosomal proteins to form the ribosomal subunits. The nucleus contains DNA that house the genes coding for the synthesis of proteins, antibodies and molecules that perform the basic functions of the cell. The nuclear membrane contains nuclear pore conplexes that allow for transport of material into and out of membrane. They also export mRNAs out of the nucleus.

2. Endoplasmic Reticulum

There are two types of endoplasmic reticulum: smooth ER and rough ER. The smooth ER is the site of lipid synthesis and some detoxification of noxious compounds. The rough ER is the site where transmembrane proteins or secreted proteins are translocated. Ribosomes are located in the rough ER instead of smooth ER because the protein has a hydrophobic signal sequence on its amino terminus. Endoplasmic Reticulum is where proteins can be modified too.

3. Mitochondrion

Mitochondria (Singular: Mitochondrion) involved in cellular energy production. It has a function in performing oxidative respiration and are found in nearly all eukaryotes. Mitochondria also produces ATP by oxidative respiration. It also has an outer and an inner membrane. Both DNA and ribosomes of mitochondria show similarities with DNA and ribosomes of bacteria.

4. Golgi Apparatus

Proteins that are not part of ER now move to the Golgi. Golgi complex has membrane stacks (cisternae) that each contain unique enzymes. Carbohydrates may be modified as proteins pass through the cisternae. Vesicles leaving the Golgi complex may fuse with the cell membrane.

5. Centriole

Centrioles are involved in a process called nuclear division. They are small, self-replicating, and are located in the cytoplasm near the nucleus. organelles present near nucleus of animal cells.

6. 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 confers the shape and rigidity to bacterial cell and helps it withstand the intracellular turgor pressure that can build up as a result of osmotic pressure.

7. Chloroplasts

Chloroplasts are only found in photosynthetic eukaryotes. They convert Sun-derived light energy to ATP and reduced NADPH. Ancient cyanobacteria gave rise to chloroplasts. In other words, cyanobacteria are the ancestor of chloroplasts. Chloroplasts have an outer membrane, an inner membrane, and the thylakoid membrane. Some algal chloroplasts have more membranes outside these. 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. Chlorophylls a and b, which are the green pigments located within plant 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 byproduct through the stomata. The dense fluid found within the chloroplast is known as the stroma, and amongst this are several interconnected membranous sacs shaped in flat discs with their own compartments, known as the thylakoids. In plants, thylakoids are arranged in a stacked conformation known as grana. Most other photosynthetic organisms and some CTemplate:Sub plant chloroplasts have unstacked thylakoids. The space within these compartments are called the thylakoid space. The membranes of the thylakoids hold the cell's chlorophyll.

8. 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.

9. Lysosome

Lysosomes are membrane enclosed organelles that help eukaryotic cells obtain nourishment from macromolecular nutrients. They contain hydrolytic enzymes. Lysosomal and phagocytosis digestion help the eukaryotic cell because they increase the membrane surface area. In eukaryotes, lysosomes allow intracellular digestion crosses the lysosomal membrane into cytoplasm. Lysosomes are the 'garbage bin' of the cell.

10. Peroxisome

Peroxisomes are the centers by which the cell may be rid of potential toxins. The peroxisomes are 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.

Cell Compartment

1. Evolution

During evolution, cells start to develop into 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 allows 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.

2. Liposomes

Liposomes are essentially lipid vesicles that are 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 that 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.

3. 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 amphiphloic 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.

Membrane Movement

A. 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. In fact, the membrane is not stable. There is a technique known as Fluorescence Recovery After Photobleaching (FRAP)assists to visualize the lateral diffusion of membrane proteins. An example of the experiment is as follow: 1) Label a specific cell component with fluorescence. 2) Use a intense beam of laser light to bleach, or destroy, the small part of the florescence labeled cell surface. 3) The intensity of bleaching recovers as the lateral diffusion of unbleached membrane proteins move into the region that has been bleached.

B. Transverse Diffusion

Transverse Diffusion describes the movement of molecules from one side the membrane to the opposite side. In comparison to the rapid movement of lateral diffusion, the speed of transverse diffusion 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

1. 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 absorbs nutrients for mitosis and duplication of DNA. Then the cells comes to mitosis phase. During this mitosis, the cell splits 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.

2. Cells Aging

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. 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.

3. Cells Death

There are two kinds of cell death: apoptosis and necrosis. Apoptosis is programmed cell death that cells that undergoes 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 disassembles. 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. On the other hand, Necrosis is unplanned cell death. It happens when the outer membrane of a cell is unable to control the liquid flowing across it. The cell is then shrink and burst. Finally, contents inside will flow out, blending into the tissues nearby. The reasons causing necrosis might be traumatic injury, infection, chemical poison, etc.

4. 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 will cause cancer.

Endocytosis

Endocytosis is the creation of internal membranes from the cell's plasma membrane lipid bilayer. It is a way for plasma membrane lipids and integral proteins to be brought inside the cell. It is thus the opposite of 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.

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 10. Slonczewski, Joan L. "Microbiology: An Evolving Science." 2009