Chem 112H Elements of Life Posters 2008

Ferritin is an iron storage protein found in the body used to regulate iron levels. Its spherical cage-like shape with a hollow center allows for elemental iron to turn into Fe(O)OH. The ferritin with mineralized iron is able to act as a photocatalyst for redox reactions. One of the reactions now studied is turning Cu²⁺ into copper colloids, though the mechanism for why this reaction takes place is not clear. Results measured by a transmission electron microscope showed that the higher the ratio of the copper ion to the ferritin, the larger the diameter of the copper colloid.

Zinc has been found to be an important metal in the brain. It serves as a moderator for gamma-aminobutyric acid (GABA), and in some cases of zinc deficiency this can lead to seizures. Zinc is most commonly observed interacting in the amygdala, an area of the brain that processes emotional reactions. Zinc is critical to long-term potentiation of neurons that process emotional responses for the brain. By inhibiting the GABAergic neurons, the zinc ions in the brain ensure long-lasting synaptic pathways.

The Calvin cycle, part of photosynthesis, is a cycle that binds atmospheric CO₂ and uses enzymes and energy to turn it into usable sugar molecules. The enzyme RuBisCO (ribulose bisphosphate carboxylase/oxylase) has a site that binds a magnesium ion and with it RuBP (ribulose bisphosphate) with a carbon dioxide molecule attached to it. This catalyzes the reaction of RuBP and CO₂ to produce two 3-carbon phosphyglycerates (3PG). When RuBisCO is activated by Mg²⁺, it gains a high affinity to RuBP-CO₂. The magnesium ion (Mg²⁺) is used in this reaction because it is a relatively small ion. Allowing it to be unique to a small binding site, with the exception of Li⁺, which has a similar size, though Mg²⁺ creates much stronger complexes that Li⁺. The magnesium ion is a positive charged which helps align the negatively charged oxygen atom on the CO₂, enzyme, and RuBP.

There are three kinds of superoxide dismutases, each of which plays a different role as an anti-oxidant. Manganese superoxide dismutase is the type that protects the mitochondria, which is an oxygen-rich environment. However, too much manganese superoxide dismutase (MSOD) may have negative effects. Polymorphism in the gene that causes expression of MSOD, however, may be linked to an increased risk in cancer, as MSOD is believed to increase the effectiveness of tumor cells, both in invasion and migration.

Cobalt is an essential trace element in the human body and the central metal ion present in vitamin B12, or cobalamin. cobalamin can only be synthesized by bacteria; animal and dairy products are the only natural sources for the active form of cobalamin. A critical function of cobalamin in the human body is as a coenzyme for the synthesis of tetrahydrofolate and methionine. Low levels of cobalamin result in the inhibition of these reactions, and as a result vitamin B12 deficient patients develop pernicious anemia and nervous system degeneration.

Before the atmospere became oxygen rich, the Earth was populated by bacteria and single-cell organisms. These organisms (such as anaerobic bacteria) needed to adapt to the harsh environments that they were in. They employed nickel in their cell functions, specifically enzymes, to manage oxidation and reduction of hydrogen. Nickel, at the time, was useful because of its physical properties as an element; specifically- its high reactivity with hydrogen. As the composition of the atmosphere changed, and life moved to dry land, nickel was replaced by other elements, such as iron, cobalt, and manganese. However, even today, nickel-containing enzymes are used in some methanogenic bacteria to convert dihydrogen and carbon dioxide into methane and water.

In their research, Meyerhoff et al. experiment with the utilization of nitric oxide (NO) as a natural inhibitor of platelet activation and adhesion, with the ultimate purpose of coating biomedical implants. Copper serves as a catalyst; immobilized copper sites interact with NO precursors, specifically nitrite and S-nitrosothiols (RSNOs), which are naturally found in human blood. After Cu(II) undergoes decomposition into Cu(I) it reacts with RSNO to release NO by transferring an electron, additionally forming a thiolate ion and regenerating Cu(II).

Hexavalent chromium, or chromium in its +6 oxidation state, has long been recognized as a human lung carcinogen. To confirm the toxic effects of Chromium (VI), J. Wise, Sr., S. Wise, and J. Little of Yale University exposed primary human bronchial fibroblasts (PHBFs) to two different hexavalent chromium salts, Na₂CrO₄ and PbCrO₄. Both compounds induced cytotoxicity by causing extensive chromosome damage, which increased with increasing concentration of the Cr (VI) salts. However, Cr (VI) is rarely found in damaged lung cells, which means there must be an alternate explanation for its toxic effects. The answer involves redox chemistry, as Cr (VI) is reduced to stable Cr (III) after entering the cell, producing unstable and harmful Cr (V/IV) complexes along the way, which can damage DNA. Most research points to Cr (V) as the main toxin; however, not all is yet known about the complex Cr (VI) to Cr (III) reduction pathways.

The study of disulfide bonds and their function in protein folding provides important information on protein structures. The oxidation-reduction chemistry for the formation of the bonds will be examined, specifically between proteins. Disulfide bonds are essential for many proteins to reach their native, or functional, state. Since most proteins will only be functional with the correct number and configuration of disulfide bonds, the way in which bonds are regulated will also be examined. Over all, the role of disulfide bonds and their advantage in strength and stability will be discussed using examples of common proteins.

Selenoproteins are proteins that contain the element selenium in the form of an amino acid called selenocysteine.  Methionine-r-sulfoxide reductase is one such selenoprotein and is also an important enzyme.  This enzyme acts as an antioxidant, repairing damage caused by oxidation of proteins.  This damage can come from common sources such as UV rays, cigarette smoke, and other carcinogens.  Oxidative damage creates free radicals, which can damage DNA, causing various forms of cancer.  The enzymes that contain selenocysteine have been found to be much more efficient in reducing methionine-r-sulfoxide, the substrate to the enzyme, than the enzyme with cysteine.  This increase can be attributed to the way the selenium interacts with the oxygen atom on the sulfoxide.  These selenium-containing enzymes are highly effective as antioxidants, which have been shown to reduce instances of cancer in clinical studies.        

Neuron-Silicon Bioelectronics

Tom Draskovic
Silicon

Elemental silicon and silicon compounds have little to no presence in most organisms, particularly bacteria and animals. Silicon is instead known for its relative chemical inertness and functions as a semiconductor. The recent technological advancement of scientists to view and work at nano-scale levels, has opened the doors to new fields of science and new capabilities of silicon in living organisms. Much like silicon semiconductor microchips in electronic devices, nerve cells can be cultured over transistors on silicon chips to create a circuit. If nerve cell circuits can be interwoven with an electronic device at a microscopic level, it is possible nerve cells could support electronic data signals. Study in this area could lead to advances in the understanding of neuronal signal processing and neuroprosthetics.

In several large clinical studies, strontium ranelate, a relatively new drug that consists of two strontium atoms bound to a ranelic acid carrier, has demonstrated very high efficacy in the treatment of osteoporosis. Strontium ranelate reverses the slow weakening of bone that comes with age, and significantly reduces the risk of dangerous and even life-threatening fracture, especially in the vertebrae and hip. It accomplishes this by means of a unique “dual mode of action”; the drug decreases resorption of bone, and at the same time increases the formation of new bone, reestablishing the metabolic balance of these two processes. The reasons for the drug’s success lie with strontium’s chemical similarity to calcium, which plays a significant role in bone metabolism and, accordingly, the onset of osteoporosis.

Calcium is most commonly associated with nutrition; however, this element also plays a crucial role in the regulation of cells and in the growth and development of plants. Through increasing the rates of photosynthesis, the absorption of ammonia, potassium, and phosphorus, and its role in reproduction, calcium has been linked to increased shoot and coleoptiles (the protective sheet around the shoot of a plant) growth. Plants that have low levels of calcium tend to have pliable cell walls, contributing to leaking of fluids. Plants with adequate calcium supplies have rigid cell walls that are able to support plants. High levels of calcium in plants are also associated with healthy leaves and fruits, whereas, low levels of calcium lead to rotting fruit and poor root development.

The majority of all the fluoride in the body is found in calcified tissues. After being absorbed into bones and teeth, it replaces the hydroxyl ion in the crystal lattice of apatite due to similarities in charge and size. Fluorapatite (Ca₅(PO₄)₃F) is more compact, less soluble, and harder to change. Although fluoride has been shown to increase bone mass, the new bone may actually have less strength due to abnormalities. Recent studies suggest that fluoride concentrations greater than 1 ppm in water may increase the likelihood of hip fractures. Danielson et al. found that residents in Brigham City, Utah, a city where the water has had a fluoride concentration of 1 ppm since 1966, had an elevated risk of hip fractures in comparison to residents of neighboring areas with a fluoridation level of .3 ppm. There has been much debate over whether fluoride is an effective treatment for osteoporosis. Fluoride has been linked to skeletal fluorosis, but yet is still used for treatment of osteoporosis. Fluoride is known to increase cancellous bone, but cause a decrease in cortical bone mineral density. It has been suggested that while immediate-release NaF reduces radial shaft bone density, slowing down the rate of fluoridation will enable new bone cells to mature and preserve radial shaft density.

Technetium-99m, isotope of Tc*, is used in Nuclear Medicine as a highly used radioactive tracer. Its 6.03 hour half life of its gamma ray emission makes it great for this use of diagnosing specific organs in the body and treating them. Because each of our organs need different forms of diagnostics and treatments, more forms are needed. Thus research is being done to form new bioactive radiopharmaceuticals to help with tracing. This is done by forming many complexes of the gamma emitting nuclide technetium 99m. The synthesis and structural analysis of the mixed-ligand Technetium (III) complex compound is great for an element of this problem. With two reduction steps, many Tc⁹⁹ complexes, including the mixed-ligand Technetium (III) complex, can be made. Biodistribution studies in rats were done to chart the brain uptakes to test for the optimal uses of Technetium.

Titanium is a substance that doesn't play any major role in life sciences; it is biocompatible. Because of this, it is a good material to use for implants because the body won't reject anything made of titanium. Also, titanium actually will have a layer of TiO₂ on the outside, acting as a corrosion- resistant barrier, and it is a light and strong metal. Some of its many medical benefits include hip replacements, screws for broken bones, bone plates, stents, heart valves, and dental uses. Specifically, it is good for implants dealing with bone because osseointegration will occur. Osseointegration is where bone will grow around a titanium implant, so it will be fused in. Surfaces that are rough or have microscopic irregularities, such as cell-size holes and bumps, will greatly increase strength because bone cells will grow right into the irregularities, helping to lock the implant in place. Bigger irregularities, like threads in a screw, help, too. Though the titanium is held in place well, there is no actual bond between it and the bone. To strengthen the implant, one can treat the surface of the titanium with something that does react with bone. The surface layer of titanium, which is actually TiO₂, reacts with hydroxyapatite at high temperature, which is what is in bone mineral. One uses plasma spraying to put the hydroxyapatite on the surface, so that when the implant is put in place, the bone not only grows around the surface, but experiments have actually found that osteoblasts, cells in the bone, will release their osteoid on it, encouraging biological attachment.

Sodium plays a key role in human and animal physiology, particularly through its involvement in ion transport. In phosphorylated-type (P-type) ion pumps, such as the sodium-potassium pump (Na⁺,K⁺-ATPase), sodium and potassium ions are driven across the plasma membranes of cells when the ion pump undergoes a perpetual process of phosphorylation and dephosphorylation. This mechanism, in turn, creates the electrical signals that are so vital to the function of brain, heart, nerve, and muscle cells. Additionally, sodium participates in the sodium-calcium exchanger (NCX), by which sodium and calcium ions are exchanged bi-directionally across the cell membrane. NCX is of particular importance in cardiac cells, which depend on calcium ion concentration to regulate muscle relaxation and contractility. Of keen interest in this presentation is the relationship between the sodium-potassium pump and NCX.

Since ancient times, epilepsy was thought to have either demonic or mystical influences. Within the last decade, however, two genes have been isolated as the cause of a type of epilepsy known as Benign Familial Neonatal Convulsions, or BFNC. The two genes, KCNQ2 and KCNQ3, transcribe for the voltage-gated potassium ion channels in the brain. Potassium channels are one of the most common transmembrane proteins in animals. It often functions in conjunction with the sodium channel and Na⁺/K⁺ ATPase pump. In neurons, this mechanism functions to send an electrical signal through the axon of a cell by causing a change in the voltage and membrane potential. Impairments in the potassium channel prevent the membrane from returning to normal (repolarization) and therefore, the cell’s repeated attempts at firing an action potential cause the visible symptoms of epilepsy. Although the genetic determinant of BFNC have been found, doctors hesitate to prescribe medication for children as the seizure symptoms are benign and short in duration.

Neurons use the charges of ions to create an electrical potential between the cells and their surroundings in order to transport messages through the nerves in the body.  Chlorine (Cl-) is found in high concentrations in the interstitial fluid, but is sometimes transported into the cell through either gamma-aminobutyric acid (GABA) receptors or cation-chlorine co-transporters (CCC).  Under normal conditions, chlorine superpolarizes neurons and creates inhibitory synaptic responses.  Under epileptic conditions, chlorine depolarizes neurons, exciting synaptic responses, and causing a seizure.  Typical epilepsy treatment focuses on the GABA receptors, but this approach has proven unsuccessful for infant epilepsy, since the way the GABA receptors function changes greatly as an individual matures.  Instead, infants respond to treatments focusing on the NKCC1 or KCC2 channels.  These channels are primarily for potassium transport, but also affect intracellular chlorine levels. 

Radioiodine ablation therapy of thyroid cancer uses the thyroid’s need for iodine to synthesize hormones to treat differentiated follicular and papillary thyroid cancer. The thyroid absorbs iodine from the bloodstream to make thyroxine and tri-iodothyronine. The radioactive iodine isotope, I-131 is absorbed into the thyroid cells in a similar manner to the non-radioactive iodine. Current research explores the conditions in which to use radioiodine treatment i.e. the dosage amount, as well as how hormones secreted by the hypothalamus, TSH, affect the radioiodine treatment.

With over half a million people dying from cancer each year, the race to find better treatments and cures is always important. There are currently only a couple methods to treat cancer, and all of them have significant side effects and/or numerous flaws. A recent discovery made by Barnett Rosenberg of the University of Michigan showed that a platinum-based molecule, cisplatin, could be used as a chemotherapy drug to kill cancer cells. Cisplatin is known to bind to the DNA molecules inside cells and to prevent cell replication. When the cell deems the DNA not repairable, the cell initiates apoptosis (cell death). As more research is being conducted, better versions of cisplatin are being discovered and developed including carboplatin and oxaliplatin.

Boron is an important micronutrient that plays a large role in the cell walls of plants. It is supplied by the soil in the form of boric acid B(OH)₃, but often soils are lacking adequate boron as is common in central Asia and various other regions around the world. Boron binds with a polysaccharide know as RG-II to help with the formation of cell walls. Stunted growth and irregular thickening of the cell wall characterize plants with a boron deficiency. In regions with boron deficient soil it is possible to use fertilizer to correct the shortage of boron and therefore increase plant growth and crop yield.

Tin protoporphyrin is an enzyme inhibitor with a complex chemical composition. One of its most important functions is that is inhibits Heme oxygenase (HO)-1 activity. Heme oxygenease is an enzyme found in both humans and animals. It is an interesting stress response that prevents oxidative damage, including ischemia and reperfusion (I/R) injury. In an experiment led by a Japanese researcher named Kaizu, mice were separated into four different groups. In one group, the mice were treated with hemin, an HO inducer. In another group, the mice were treated with a low dose of SnPP and in another group, mice were treated with a high dose of SnPP. Results disproved former beliefs that hemin increases HO-1 activity and SnPP significantly ameliorates HO-1 activity and ends up hurting the cell. However these new results show that a high dose of SnPP actually increases the HO-1 activity, which then decreases stress in cells such as the ones from the kidney. This high dosage of SnPP, which can induce HO-1 activity also has medical benefits in sickle cell disease and postnatal jaundice patients.

Mercury is a toxic heavy metal that can cause serious harm to the human body. There are three different forms of mercury that can poison the body and each of these forms targets different body systems and causes different symptoms. There are ways to treat mercury poisoning and remove it from the body. This is usually done by chelating agents. Two of the major drugs available today that treat heavy metal poisoning include DMSA, also known as Chemet, and DMPS, also known as Dimaval. These compounds are both water soluble and therefore can easily dissolve and circulate throughout the body. The minimum binding ratio between the compounds and mercury is 2 DMSA or DMPS for every 2 mercury ions. Both drugs act in the kidney, which is where heavy metals such as mercury can be brought and settle. These compounds treat poisoning by certain types of mercury better than others mostly because of the way in which the compounds are delivered into the body. DMSA and DMPS contain sulfhydryl groups which mercury has a high affinity. Because of this high affinity for sulfhydryl groups, mercury binds to these for compounds and the compounds then exit the body, usually through the urine.