How Structure Relates to Function: The Biological Cell A peroxisome uses oxygen inside the cell to oxidize organic molecules. It also has enzymes that produce and break down hydrogen peroxide ie. RH02 + 02 > R + H202; where R equals an organic substrate. Proteins are brought into peroxisomes selectively. A defect of this selectivity causes Zellweger Syndrome. In this dysfunction, proteins are being brought into empty peroxisomes and are not being oxidized. It presents as a failure to thrive, liver problems, and possible mental retardation. The prognosis is grim, and very little can be done. Recent developments in research include prenatal diagnosis (Nelson and Cox 839). Another word ending in “some” is a lysosome. It typically contains digestive enzymes at an acidic pH. Although examples of reactions for this component were not found, it often turns acts as a hydrolytic, making an -ose an -ase. The acidic pH is maintained by at an acidic pH by ATPase around the membrane that places H+ into the lumen. A lysosome also processes GAA, which is needed to break down glycogen (Nelson and Cox 222). A loss of this function impairs the cells metabolism, and could cause Pompe’s disease. New research shows that lysosomes do not choose which cells will have apoptosis (preprogrammed cell death), as previously assumed (Lysosome). Now that the “somes” are over with, I bring the oft-neglected extracellular matrix (ECM). The ECM is a bunch of polysaccharides and proteins that are released by the cell. The ECM also involves heterophilic particles called integrins which bind to the cytoskeleton. Biochemically, a repeating dissacharide of glucuronic acid and N-acetylglucosamine (components of the ECM) have negative charged side groups and are amino-sugars (Nelson and Cox 1007). In Alzheimer’s disease there is dysfunction in ECM adhesion, especially in the synapses of the brain. In addition, research in the Brazilian Journal of Medicine shows that brown recluse spider venom adheres to the ECM and the proteins in the ECM activate the venom (Brazz et al.). Another major addition to the cell is the Golgi apparatus. Proteins and lipids in this membrane-bound organelle are modified and sorted. The endoplasmic reticulum shares a face with the Golgi body. A major biochemical component of this sharing involves glycosylation. “For N -linked oligosaccharides, a 14-sugar precursor is first added to the asparagine in the polypeptide chain of the target protein”(Glycosylation). Plasma b cells have giant Golgi bodies. Lack of these cells causes one to be immunodeficient, causing a garden variety of illnesses. Arthritis patients often have a high level of Golgi body antigens, causing necrosis of cells in joints, as proven in the Arthritis Research journal (Casiano et al.). One piece of information not included in the textbook’s drawing is the plasma membrane. The function of this is to be a selectively permeable entity on the outer layer of a cell comprised of biochemical pumps, phospholipids and proteins. A key biochemical component of an animal cell’s plasma membrane besides its active and passive transport is its cell potential. The Nernst equation is used to determine the resting equilibrium potential of a cell, especially K+ ions. Very few cell membrane proteins have been discovered, but NhaA is a new protein on the forefront of research (Nelson and Cox 1291). Researchers at Hebrew University discovered a way to manipulate the gene that makes this type of protein and replicate it. It is important to understand how this type of protein works, because the mystery of cystic fibrosis has yet to be solved (Hebrew University Life Sciences). Cystic fibrosis is caused by a defect in the cell membrane, more specifically; the calcium ion gradient (Reed). More complex than the plasma membrane is the seemingly simple intermediate filaments. In reality, there are five kinds of I.F.s based on where the cell is located in the body eg. Skin, nails, organs etc. Plainly, these structures are a part of the cytoskeleton, which supports the cell’s structure. Assuming one knows nothing about biochemistry, these structures are exceedingly complex. For example, the central rod of a nuclear lamin (a type of intermediate filament which is found in most body structures) has (NH2)-Pro-Pro-Lys-Lys-Lys-Arg-Lys-Val-(COOH), which seems like to the author of this paper several amino acids in a chain with organics at the ends. This is called a nuclear localization signal, which is important in “tagging” the molecule in studies of molecular function. I’ll leave it at that, and move on to the disease processes involving this specific type of I.F: laminopathies. Laminopathic diseases include Hutchinson Gilford Progeria Syndrome . This causes accelerated aging due to a defect in cell division on the first chromosome, specifically on the Lamin A protein (Nelson and Cox 771).
Perhaps a cell structure slightly less exhausting is in the cards. For instance, the cytoplasm is made up of saltish brine and enzymes that hold together all the ingredients of a cell (cytosol). It is surrounded by the plasma membrane. There is an enzyme in the cytoplasm called Ape1 required for autophagy. ” Autophagy is an essential process that allows cell survival under certain stress conditions…. Autophagic dysfunction is associated with various diseases in humans including cancer and neurodegenrative diseases such as Parkinson’s and Alzheimer’s disease” (U-Michigan Biology Dept). The difficult part about enzyme reactions is their biochemistry. In order for cytosol to work, there must be pathways. These pathways use AtG proteins which bond to one another using phosphatidylethanolamine to form covalent bonds (Nelson and Cox 208). Microtubules are part of the cytoskeleton as well. They help the cell moves and are involved in mitosis. There is both and alpha and beta subunit. Very, very simply described: For energy transfer, alpha and beta subunits are bound to Guanosine triphosphate. Only the alpha unit is stable, and the beta unit goes into hydrolysis. When hydrolysis catches up to the whole molecules it is unstable, it shrinks, causing “catastrophe.” The process can then add new subunits, and this is called rescue. This process is preyed upon by anti-cancer drugs. Taxane drugs block catastrophe (Nelson and Cox 932). Research at the Scripps Institute identified kenesin using cryoelectronics, which helps the cell move. The opposite of kenesin is a newly-discovered protein called Ncd, and it reverses the movement of kenesin, although researchers are unsure of the mechanism (UC-SF Vale Laboratory). Centrosomes are closely related to microtubules. Centrosomes assist in cell division, although recent research has shown that they are not necessary. This most important chemical in centrosome reactions is cyclin-dependent kinase. Different cdk complexes trigger differing steps in the cell division cycle by phosphorylating target proteins. Dr. Stephen Doxsey is investigating novel proteins from centrosomes that have been found to affect scleroderma, an autoimmune disease (UMass Medical Center). Next are ribosomes. These organelles translate messenger RNA into proteins. Regardless of where they are located in a cell, some ribosomes are eukaryotic and prokaryotic. This is important to humans because it allows certain drugs such as antibiotics to target proteins of non-human cells. In terms of genetic biochemistry, two adaptors must be to translate mRNA. The first, aminoacyl-tRNA (translate RNA)
synthetase, is used in a process called charging. An anticodon is then used in the second adaptor. For instance, tryptophan is linked to tRNA with a high energy bond. The net result is that the amino acid is base paired to the overall protein chain. Recent research involves the development of a specific antibiotic to combat methicillin resistant S. aureus (Nelson and Cox 1023). The double membrane surrounding the nucleus is the nuclear envelope. In a function similar to the cell membrane, it facilitates transport betweens the cytoplasm and nucleus through channels called nuclear pores. At some point it becomes necessary, albeit boring, to discuss active transport. Primary transport uses energy and enzymes called ATPases in the sodium-potassium pump. In secondary transport, the electrochemical difference is caused by pumping ions out of the cell itself. Diseases in the nuclear envelope also involve laminopathies. A research project by Forbes at UC-SD states that two nuclear import pathways converge on one nuclear pore, nuclear pore 153. “Dominant-negative fragments of Nup153 can now be used to distinguish different nuclear import pathways.” Laminopathies are also caused by this structure. Connected to the nuclear envelope is the endoplasmic reticulum (ER). There are two types: smooth and rough. The latter manufactures and transports proteins while the former detoxifies and synthesizes nutrients. The rough ER has ribosomes. Both ERs need to correctly fold and transport specific proteins. For example, calnexin is an integral protein of the ER whose function is to retain glycoproteins, specifically GlcNAc2Man9Glc1 oligosaccharides. Asparaginine is then added along with glucosidase to fold the protein. If it is still folded wrong, an enzyme called UGGT refolds it. Only after this process is calnexin available to move the protein along its distant and winding path through the ER (Nelson and Cox 305). Also, disease can be caused relating to the ER. For instance, ER in muscles is surrounded myosin. These ER are called sarcoplasmic reticulum, and defects in these cause dumping of calcium and involuntary muscle contractions (aka Parkinson’s). Research in the Journal of Biochemistry shows that high calcium levels can cause apoptosis due to modification of an enzyme in the ER, caspase-12 ( (Boo et al. 407). Vesicles have different properties and are diverse. They can transport, digest cellular enzymes and waste products. Pathologically, lysosome vesicles have a role in inclusion cell disease. Enzymes are routed out of the cells using these vesicles. Researchers at Cornell University are studying how neurotransmitters
are dumped into vesicles between synapses. Vesicles that bud from a membrane carry specific marker proteins called vesicle SNAREs on their surfaces, which bind to target SNAREs. The actin filaments determine the movement and structure of a cell. It used in junction with myosin in muscle cells to contract the muscle. Actin filaments are derived from actin, which is polymerized by a process called nucleation. Individual units of the actin make a trimer (three non-covalent macromolecules). Actin units are polar, so ATP-actin tends to bind the positive end. Concurrently, the P group is hydrolyzed and is released. The cell then recognizes the trimer is unstable and begins to make more ATP-actin units. Proteins capfilin and CapZ can prevent this process in some parts of the body. Rod myopathy is a genetic disorder that affects chromosome 1q42.1. The actin gene is deformed to produce small “rods” in the muscles, which is a byproduct and not a cause of the disease. It causes weakness of limbs and most importantly, respiratory function. Many a years ago it was shown that destroying microtubules affects cell movement (hence, actin). An article from the Scripps Research institute states: “The mechanism of this [actin relation to microtubules] is unclear. ‘What is clear,’ says [Dr.]Waterman-Storer, ‘is that we can image them simultaneously to look for evidence if interactions between the two.’” The last exonuclear structures are the mitochondria. This structure powers the cell using ATP and oxidative phosphorylation, which is as follows: ADP 3- + H + + P i ↔ ATP 4- + H 2 O. It also contains enzymes involved in many activities around the cell. Mitochondria play roles apoptosis, redox reactions, in addition to iron and steroid synthesis (Mitochondrion). Diseases of mitochondrial dysfunction include a plethora of neuromuscular disorders caused by cell death. One of the simplest to treat is L-Carnitine deficiency, which has a treatment of additional carnitine in the diet (United Mitochondrial Research Foundation). Mitochondria defects in identifiable alleles have shown remarkable defects in sperm (Ancobia Genetics Ltd). Inside the nucleus, chromatin is vital in DNA creation and repair. It also produces proteins called histones, which regulate gene expression. Biochemistry involves the famous Watson-Crick theory of DNA. Between a sugar and base there is of course the cytosine and guanine and adenine and tyrosine. The structure of DNA is made by purine and pyrimidine. These molecules cause anti- and syn- sides of the
DNA molecule. In the September 11, 2006 issue of Molecular Reproductive Development, Adham et al. showed that inadequate chromatin condensation causes sperm abnormalities (no, this is not a repeat of the above paragraph). Last but certainly not least is the cell nucleus and nucleolus. The function of the nucleus is to control the structures inside of the cytoplasm as well as cellular division. The nucleolus is inside the nucleus, and has a proximity to the ER. It packages and sends RNA and ribosomes. One of the steps in nucleolus packaging uses RNA polymerase, which is prepared by a lengthy process using proteins to initiation (molecule construction), elongation (RNA writing) and termination (stopping of both of the aforementioned processes (Nelson and Cox 300). Defects in the nucleus can cause unstable genomes, which is a breeding ground for Werner’s syndrome (Dellaire). Now to the good stuff, the nucleus. Focusing on cytoplasmic enzymes, pre-mRna is subject to 5′ capping, 3′ polydenylation and RNA splicing. Capping ensures stability of RNA; polydenylation ensures correct termination of the ends of molecule. RNA splicing uses spliceosomes, catalysts, to transcribe excess exons. Another function of nuclear transport is to use importins and exportins. The previously mentioned NLS is utilized in importins. These karyopherins are regulated by (guanosine triphosphate) GTPase. A GTPase specific to this function is Ran. Plainly, Ran eventually changed GTP to GDP in nuclear import. This process allows the import to release into the nucleus. The process is the opposite in exportation because the GTPase Activating Protein binds the needed exports using the Ran-GDP process. Referring to cell division, once and a while the somatic eukaryotic cell goes into mitosis. When the cell reforms, is nuclear lamina reassembled by dephosphorylation (Cell Nucleus). An easy way to describe a disease involving the nucleus is a herpesvirus. This uses its DNA to assemble in a host nucleus while disassembling nuclear lamins to get out of the nucleus. The Herpesvirus Research group says that herpesviruses use an unusual way to get to the nuclear center. It is not similar to the exportin and importin process, but how this virus tagging process is completed is unknown (Herpesvirus Research Group).